Login Register Cart 0
Generic placeholder image

Current Organic Synthesis

Editor-in-Chief

ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Advances in Synthesis, Derivatization and Bioactivity of Isatin: A Review

Author(s): Garima Chauhan*, Dharam Pal Pathak, Faraat Ali, Rubina Bhutani, Garima Kapoor and Shaik Khasimbi

Volume 18, Issue 1, 2021

Published on: 24 September, 2020

Page: [37 - 74] Pages: 38

DOI: 10.2174/1570179417666200924150907

Price: $65

Abstract

Background: Isatin (IST) is a crucial pharmacologically active compound, chemically known as indole- 1H-2,3-dione. Development of different IST based analogues acquired significant awareness because of its pronounced therapeutic importance such as analgesic, anticancer, anti-inflammatory, antitubercular, antimicrobial, antifungal, antiviral (effective against SARS coronavirus 3C protease) and many other activities, and represents an important class of heterocyclic compounds that can be used as a precursor for the synthesis of many useful drugs.

Objective: Previously, many articles were reported on IST synthesis and its different pharmacological activities but herein, we mentioned 59 different synthesis schemes of several IST derivatives/hybrids derived from the substitution of the nitrogen, aromatic ring, the second and third position of IST along with most potent molecule among each of synthesized libraries with their structural activity relationship (SAR). Using these standardized approaches, several biologically important compounds were developed like sunitinib, nintedanib, indirubin, etc and several studies have been carried out nowadays to develop newer compounds having fewer side effects and also overcome the problem of resistance.

Conclusion: This report critically reviews the different strategies for the designs and synthesis of several IST based compounds having different biological activities with SAR, which can favour further investigation and modification for the development of new and more potent entities.

Keywords: Antitubercular, antiviral, anticancer, anticonvulsant, anti-inflammatory, analgesic, Isatin.

« Previous Next »
Graphical Abstract

[1]
Guo, Y.; Chen, F. Zhongcaoyao. 1986, 17. CA (Edinb.), 1986. 104213068f
[2]
Bergman, J.; Lindström, J.O.; Tilstam, U. The structure and properties of some indolic constituents in Couroupita guianensis aubl. Tetrahedron, 1985, 41, 2879-2881.
[http://dx.doi.org/10.1016/S0040-4020(01)96609-8]
[3]
Erdmann, O.L. Untersuchungen über den Indigo. J. Prakt. Chem., 1840, 19, 321-362.
[http://dx.doi.org/10.1002/prac.18400190161]
[4]
Laurent, A. Recherches sur l’indigo. Ann. Chim. Phys., 1840, 3, 393-434.
[5]
Pandeya, S.N.; Smitha, S.; Jyoti, M.; Sridhar, S.K. Biological activities of isatin and its derivatives. Acta Pharm., 2005, 55(1), 27-46.
[PMID: 15907222]
[6]
Medvedev, A.; Buneeva, O.; Gnedenko, O.; Ershov, P.; Ivanov, A. Isatin, an endogenous nonpeptide biofactor: A review of its molecular targets, mechanisms of actions, and their biomedical implications. Biofactors, 2018, 44(2), 95-108.
[http://dx.doi.org/10.1002/biof.1408] [PMID: 29336068]
[7]
Wei, L.; Wang, Q.; Liu, X. Application of thin-layer chromatography in quality control of Chinese medicinal preparations. II. Qualitative analysis of some Chinese medicinal preparations of Chansu. Yaowu Fenxi Zazhi., 1982, 2(CA 98) 95726b
[8]
Baeyer, A. Ueber die Verbindungen der Indigogruppe. Ber. Dtsch. Chem. Ges., 1883, 16, 2188-2204.
[http://dx.doi.org/10.1002/cber.188301602130]
[9]
Gräfe, U.; Radics, L. Isolation and structure elucidation of 6-(3′-methylbuten-2′-yl)isatin, an unusual metabolite from Streptomyces albus. J. Antibiot. (Tokyo), 1986, 39(1), 162-163.
[http://dx.doi.org/10.7164/antibiotics.39.162] [PMID: 3949628]
[10]
Schunck, E. Notes on the purple of the ancients. J. Chem. Soc., 1879, 35, 589-596.
[http://dx.doi.org/10.1039/CT8793500589]
[11]
Vine, K.L.; Matesic, L.; Locke, J.M.; Ranson, M.; Skropeta, D. Cytotoxic and anticancer activities of isatin and its derivatives: a comprehensive review from 2000-2008. Anticancer. Agents Med. Chem., 2009, 9(4), 397-414.
[http://dx.doi.org/10.2174/1871520610909040397] [PMID: 19442041]
[12]
Breinholt, J.; Demuth, H.; Heide, M.; Jensen, G.W.; Moller, I.L.; Nielsen, R.I.; Olsen, C.E.; Rosendahl, C.N. Prenisatin (5-(3-Methly-2-butenyl)-indole-2, 3-dione): An Antifungal Isatin Derivative from Chaetomium globosum. Acta Chem. Scand., 1996, 50, 443-445.
[http://dx.doi.org/10.3891/acta.chem.scand.50-0443]
[13]
Schunck, E. Notes on the purple of the ancients. 1. The chromogen of Purpura capillus. 2. Properties of the colouring matter formed by insolation from the chromogen of Purpura capillus. J. Chem. Soc., 1879, 35, 589-596.
[http://dx.doi.org/10.1039/CT8793500589]
[14]
Letellier, A. Recherches sur la pourpre produite par le Purpura lapillus. Arch. Zool. Exp. Gén., 1890, 8, 361-403.
[15]
Baker, J.T.; Sutherland, M.D. Pigments of marine animals. VIII. Precursors of 6,6'dibromoindigotin (tyrian purple) from the mollusc Dicathais orbita gmelin. Tetrahedron Lett., 1968, 9, 43-46.
[http://dx.doi.org/10.1016/S0040-4039(01)98723-4]
[16]
Benkendorff, K.; Bremner, J.B.; Davis, A.R. Indole derivatives from the egg masses of Muricid molluscs. Molecules, 2001, 6, 70-78.
[http://dx.doi.org/10.3390/60100070]
[17]
Kapadia, G.J.; Shukla, Y.N. Basak. S.P.; Sokoloski, E.A.; Fales, H. M. The melo- satins a novel class of alkaloids from melochia tomentosa. Tetrahedron, 1980, 36, 2441-2447.
[http://dx.doi.org/10.1016/0040-4020(80)80221-3]
[18]
Kapadia, G.J.; Shukla, Y.N.; Melosatin, D.; Melosatin, D. A New Isatin Alkaloid from Melochia tomentosa Roots. Planta Med., 1993, 59(6), 568-569.
[http://dx.doi.org/10.1055/s-2006-959766] [PMID: 17230369]
[19]
Hamaue, N.; Yamazaki, N.; Minami, M.; Endo, T.; Hirafuji, M.; Monma, Y.; Togashi, H.; Saito, H.; Parvez, S.H. Effect of isatin, an endogenous MAO inhibitor, on acetylcholine and dopamine levels in the rat striatum. Biog. Amines, 1999, 15, 367-377.
[20]
Gillam, E.M.J.; Notley, L.M.; Cai, H.; De Voss, J.J.; Guengerich, F.P. Oxidation of indole by cytochrome P450 enzymes. Biochemistry, 2000, 39(45), 13817-13824.
[http://dx.doi.org/10.1021/bi001229u] [PMID: 11076521]
[21]
Vine, K.L.; Matesic, L.; Locke, J.M.; Ranson, M.; Skropeta, D. Recent highlights in the development of isatin based anticancer agent. Anti-Cancer Agent Me, 2009, 9, 397-414.
[http://dx.doi.org/10.2174/1871520610909040397]
[22]
Palenik, G.J.; Koziol, A.E.; Katritzky, A.R.; Fan, W.Q. Nonbonded interactions. The influence of lone pair repulsions on bond lengths. J. Chem. Soc. Chem. Commun., 1990, 715.
[http://dx.doi.org/10.1039/c39900000715]
[23]
Frolova, N.A.; Kravtsov, V.K.; Biyushkin, V.N.; Chumakov, Y.M.; Belkova, O.N.; Malinovskii, T.I. Zh. Strukt. Khim. 1988, 29, 155.
[24]
Silva, J.F.M.; Garden, S.J.; Pinto, A.C. The Chemistry of Isatins: a Review from 1975 to 1999. J. Braz. Chem. Soc., 2001, 12, 273-324.
[http://dx.doi.org/10.1590/S0103-50532001000300002]
[25]
Gassman, P.G.; Cue, B.W., Jr; Luh, T.Y. A general method for the synthesis of isatins.” The Journal of Organic Chemistry J. Org. Chem., 1977, 42, 1344.
[http://dx.doi.org/10.1021/jo00428a016]
[26]
Albright, T.A.; Freeman, W.J. Nuclear magnetic resonance studies: VII—13C and 15N nmr of diazo compounds. Org. Magn. Res, 1977, 9, 75.
[http://dx.doi.org/10.1002/mrc.1270090206]
[27]
Galasso, V.; Pellizer, G.; Pappalardo, G.C. Carbon‐13 nmr and CNDO/S study of 1, 2‐indandione and heterocyclic analogues. Org. Magn. Res, 1977, 9, 401.
[http://dx.doi.org/10.1002/mrc.1270090706]
[28]
Winkler, T.; Ferrini, P.G.; Haas, G. The 13C NMR spectrum of coumarandione. Org. Magn. Res., 1979, 12, 101.
[http://dx.doi.org/10.1002/mrc.1270120213]
[29]
Sin, N.; Venables, B.L.; Combrink, K.D.; Gulgeze, H.B.; Yu, K.L.; Civiello, R.L.; Thuring, J.; Wang, X.A.; Yang, Z.; Zadjura, L.; Marino, A.; Kadow, K.F.; Cianci, C.W.; Clarke, J.; Genovesi, E.V.; Medina, I.; Lamb, L.; Krystal, M.; Meanwell, N.A. Respiratory syncytial virus fusion inhibitors. Part 7: structure-activity relationships associated with a series of isatin oximes that demonstrate antiviral activity in vivo. Bioorg. Med. Chem. Lett., 2009, 19(16), 4857-4862.
[http://dx.doi.org/10.1016/j.bmcl.2009.06.030] [PMID: 19596574]
[30]
Abbas, S.Y.; Farag, A.A.; Ammar, Y.A.; Atrees, A.A.; Mohamed, A.F.; El-Henawy, A.A. Synthesis, characterization, and antiviral activity of novel fluorinated isatin derivatives. Monatsh. Chem., 2013, 144(11), 1725-1733.
[http://dx.doi.org/10.1007/s00706-013-1034-3] [PMID: 32214479]
[31]
Zhang, H.M.; Dai, H.; Hanson, P.J.; Li, H.; Guo, H.; Ye, X.; Hemida, M.G.; Wang, L.; Tong, Y.; Qiu, Y. Liu. S.; Wang, F.; Song, F.; Zhang, B.; Wang, J. G.; Zhang, L. X.; Yang, D. Antiviral activity of an isatin derivative via induction of PERKNrf2-mediated suppression of cap-independent translation. ACS Chem. Biol., 2014, 9, 1015-1024.
[http://dx.doi.org/10.1021/cb400775z] [PMID: 24547890]
[32]
Paira, P.; Hazra, A.; Kumar, S.; Paira, R.; Sahu, K.B.; Naskar, S.; Saha, P.; Mondal, S.; Maity, A.; Banerjee, S.; Mondal, N.B. Efficient synthesis of 3,3-diheteroaromatic oxindole analogues and their in vitro evaluation for spermicidal potential. Bioorg. Med. Chem. Lett., 2009, 19(16), 4786-4789.
[http://dx.doi.org/10.1016/j.bmcl.2009.06.049] [PMID: 19564109]
[33]
Quraishi, M.A.; Ahamad, I.; Singh, A.K.; Shukla, S.K.N. - (Piperidinomethyl)-3-[(pyridylidene)amino]isatin: A new and effective acid corrosion inhibitor for mild steel. Mater. Chem. Phys., 2008, 3, 1035-1039.
[http://dx.doi.org/10.1016/j.matchemphys.2008.07.011]
[34]
Figueiredo, G.S.; Zardo, R.S.; Silva, B.V.; Violante, F.A.; Pinto, A.C.; Fernandes, P.D. Convolutamydine A and synthetic analogues have antinociceptive properties in mice. Pharmacol. Biochem. Behav., 2013, 103(3), 431-439.
[http://dx.doi.org/10.1016/j.pbb.2012.09.023] [PMID: 23046852]
[35]
González, A.; Quirante, J.; Nieto, J.; Almeida, M.R.; Saraiva, M.J.; Planas, A.; Arsequell, G.; Valencia, G. Isatin derivatives, a novel class of transthyretin fibrillogenesis inhibitors. Bioorg. Med. Chem. Lett., 2009, 19(17), 5270-5273.
[http://dx.doi.org/10.1016/j.bmcl.2009.03.004] [PMID: 19651509]
[36]
Andreani, A.; Burnelli, S.; Granaiola, M.; Leoni, A.; Locatelli, A.; Morigi, R.; Rambaldi, M.; Varoli, L.; Cremonini, M.A.; Placucci, G.; Cervellati, R.; Greco, E. New isatin derivatives with antioxidant activity. Eur. J. Med. Chem., 2010, 45(4), 1374-1378.
[http://dx.doi.org/10.1016/j.ejmech.2009.12.035] [PMID: 20060202]
[37]
Naik, N.; Vijay, K.H.; Vidyashree, P.B. Synthesis and evaluation of antioxidant potential of novel isatin analogues. J. Pharm. Res., 2011, 4, 2686-2689.
[38]
Manley-King, C.I.; Bergh, J.J.; Petzer, J.P. Inhibition of monoamine oxidase by selected C5- and C6-substituted isatin analogues. Bioorg. Med. Chem., 2011, 19(1), 261-274.
[http://dx.doi.org/10.1016/j.bmc.2010.11.028] [PMID: 21134756]
[39]
Prakash, C.R.; Raja, S. Design, synthesis and antiepileptic properties of novel 1-(substituted benzylidene)-3-(1-(morpholino/piperidino methyl)-2,3-dioxoindolin-5-yl)urea derivatives. Eur. J. Med. Chem., 2011, 46(12), 6057-6065.
[http://dx.doi.org/10.1016/j.ejmech.2011.10.020] [PMID: 22037252]
[40]
Kandasamy, R.; Park, S.J.; Boyapalle, S.; Mohapatra, S.; Hellermann, G.R.; Lockey, R.F.; Mohapatra, S.S. Isatin down-regulates expression of atrial natriuretic peptide receptor A and inhibits airway inflammation in a mouse model of allergic asthma. Int. Immunopharmacol., 2010, 10(2), 218-225.
[http://dx.doi.org/10.1016/j.intimp.2009.11.003] [PMID: 19900583]
[41]
Chen, G.; Wang, Y.; Hao, X.; Mu, S.; Sun, Q. Simple isatin derivatives as free radical scavengers: Synthesis, biological evaluation and structure-activity relationship. Chem. Cent. J., 2011, 5, 37-41.
[http://dx.doi.org/10.1186/1752-153X-5-37] [PMID: 21722377]
[42]
Khan, K.M.; Mughal, U.R.; Khan, A.; Naz, F.; Perveen, S.; Choudhary, M.I. N-Aroylated Isatins: Antiglycation Activity. Lett. Drug Des. Discov., 2010, 7, 188-193.
[http://dx.doi.org/10.2174/157018010790596597]
[43]
Raj, R.; Gut, J.; Rosenthal, P.J.; Kumar, V. 1H-1,2,3-Triazole-tethered isatin-7-chloroquinoline and 3-hydroxy-indole-7-chloroquinoline conjugates: synthesis and antimalarial evaluation. Bioorg. Med. Chem. Lett., 2014, 24(3), 756-759.
[http://dx.doi.org/10.1016/j.bmcl.2013.12.109] [PMID: 24424135]
[44]
Tarun kumar, N. A.; Jignesh, P. R. New carbodithioate derivatives: synthesis, characterization, and in vitro antibacterial, antifungal, antitubercular, and antimalarial activity. Med. Chem. Res., 2013, 22, 4700-4707.
[http://dx.doi.org/10.1007/s00044-013-0472-0]
[45]
Kumar, K.; Pradines, B.; Madamet, M.; Amalvict, R.; Benoit, N.; Kumar, V. 1H-1,2,3-triazole tethered isatin-ferrocene conjugates: Synthesis and in vitro antimalarial evaluation. Eur. J. Med. Chem., 2014, 87, 801-804.
[http://dx.doi.org/10.1016/j.ejmech.2014.10.024] [PMID: 25440881]
[46]
Shahlaei, M.; Fassihi, A.; Nezami, A. QSAR study of some 5-methyl/trifluoromethoxy- 1H-indole-2,3-dione-3-thiosemicarbazone derivatives as anti-tubercular agents. Res. Pharm. Sci., 2009, 4(2), 123-131.
[PMID: 21589807]
[47]
Karah, N.; Terzioĝlu, N.; Gürsoy, A. Synthesis and structure-activity relationships of 3-hydrazono-1H-2-indolinones with antituberculosis activity. Arzneimittelforschung, 1998, 48(7), 758-763.
[PMID: 9706377]
[48]
Kumar, K.; Carrere-Kremer, S.; Kremer, L.; Guerardel, Y.; Biot, C.; Kumar, V. 1H-1,2,3-triazole-tethered isatin-ferrocene and isatin-ferrocenylchalcone conjugates: synthesis and in vitro antitubercular evaluation. Organometallics, 2013, 32, 110-116.
[http://dx.doi.org/10.1021/om301157z]
[49]
Liu, B.; Wang, G.Q.; Peng, Y.H.; Tang, X.Q.; Hu, G.W. Design, synthesis, and in vitro antimycobacterial activities of butylene tethered 7‐fluoroisatin‐isatin scaffolds. J. Heterocycl. Chem., 2019, 56, 3423-3428.
[http://dx.doi.org/10.1002/jhet.3696]
[50]
Feng, L.S.; Liu, M.L.; Wang, B.; Chai, Y.; Hao, X.Q.; Meng, S.; Guo, H.Y. Synthesis and in vitro antimycobacterial activity of balofloxacin ethylene isatin derivatives. Eur. J. Med. Chem., 2010, 45(8), 3407-3412.
[http://dx.doi.org/10.1016/j.ejmech.2010.04.027] [PMID: 20493593]
[51]
Talath, S.; Bhongade, B.A. Synthesis, antimicrobial and anticancer studies of isatin derivatives of sparfloxacin. Am. PharmTech Res, 2013, 3, 570-581.
[52]
Karali, N.; Gürsoy, A.; Kandemirli, F.; Shvets, N.; Kaynak, F.B.; Ozbey, S.; Kovalishyn, V.; Dimoglo, A. Synthesis and structure-antituberculosis activity relationship of 1H-indole-2,3-dione derivatives. Bioorg. Med. Chem., 2007, 15(17), 5888-5904.
[http://dx.doi.org/10.1016/j.bmc.2007.05.063] [PMID: 17561405]
[53]
Sriram, D.; Yogeeswari, P.; Meena, K. Synthesis, anti-HIV and antitubercular activities of isatin derivatives. Pharmazie, 2006, 61(4), 274-277.
[http://dx.doi.org/10.1002/chin.200629154] [PMID: 16649536]
[54]
Abadi, A.H.; Abou-Seri, S.M.; Abdel-Rahman, D.E.; Klein, C.; Lozach, O.; Meijer, L. Synthesis of 3-substituted-2-oxoindole analogues and their evaluation as kinase inhibitors, anticancer and antiangiogenic agents. Eur. J. Med. Chem., 2006, 41(3), 296-305.
[http://dx.doi.org/10.1016/j.ejmech.2005.12.004] [PMID: 16494969]
[55]
Uddin, M.K.; Reignier, S.G.; Coulter, T.; Montalbetti, C.; Grånäs, C.; Butcher, S.; Krog-Jensen, C.; Felding, J. Syntheses and antiproliferative evaluation of oxyphenisatin derivatives. Bioorg. Med. Chem. Lett., 2007, 17(10), 2854-2857.
[http://dx.doi.org/10.1016/j.bmcl.2007.02.060] [PMID: 17368900]
[56]
Matesic, L.; Locke, J.M.; Bremner, J.B.; Pyne, S.G.; Skropeta, D.; Ranson, M.; Vine, K.L. N-phenethyl and N-naphthylmethyl isatins and analogues as in vitro cytotoxic agents. Bioorg. Med. Chem., 2008, 16(6), 3118-3124.
[http://dx.doi.org/10.1016/j.bmc.2007.12.026] [PMID: 18182300]
[57]
Smitha, S.; Pandeya, S.N.; Stables, J.P.; Ganpathy, S. Anticonvulsant and sedative-hypnotic activities of N-Acetyl/Methyl isatin derivatives. Sci. Pharm., 2008, 76, 621-636.
[http://dx.doi.org/10.3797/scipharm.0806-14]
[58]
Verma, M.; Pandeya, S.N.; Singh, K.N.; Stables, J.P. Anticonvulsant activity of Schiff bases of isatin derivatives. Acta Pharm., 2004, 54(1), 49-56.
[PMID: 15050044]
[59]
Singh, G.S.; Siddiqui, N.; Pandeya, S.N. Synthesis and anticonvulsant and anti-inflammatory activities of new 3-aryl/alkylimino-1-methylindol-2-ones. Arch. Pharm. Res., 1992, 15, 272-274.
[http://dx.doi.org/10.1007/BF02974069]
[60]
Bal, T.R.; Anand, B.; Yogeeswari, P.; Sriram, D. Synthesis and evaluation of anti-HIV activity of isatin beta-thiosemicarbazone derivatives. Bioorg. Med. Chem. Lett., 2005, 15(20), 4451-4455.
[http://dx.doi.org/10.1016/j.bmcl.2005.07.046] [PMID: 16115762]
[61]
Sriram, D.; Bal, T.R.; Yogeeswari, P. Aminopyrimidinimino isatin analogues: design of novel non- nucleoside HIV-1 reverse transcriptase inhibitors with broad-spectrum chemotherapeutic properties. J. Pharm. Pharm. Sci., 2005, 8(3), 565-577.
[PMID: 16401403]
[62]
Nandakumar, A.; Thirumurugan, P.; Perumal, P.T.; Vembu, P.; Ponnuswamy, M.N.; Ramesh, P. One-pot multicomponent synthesis and anti-microbial evaluation of 2′-(indol-3-yl)-2-oxospiro(indoline-3,4′-pyran) derivatives. Bioorg. Med. Chem. Lett., 2010, 20(14), 4252-4258.
[http://dx.doi.org/10.1016/j.bmcl.2010.05.025] [PMID: 20621732]
[63]
Sarangapani, M.; Reddy, V.M. Synthesis and antimicrobial activity of 1-[(N, N-disubstituted amino) methyl]-3-[(2-phenyl-3, 4-dihydro-4-oxoquinazoline-3-yl] indole-2-one. Indian J. Heterocycl. Chem., 1994, 3, 257-260.
[64]
Ravichandran, V.; Mohan, S.; Kumar, S.K. Synthesis and antimicrobial activity of Mannich bases of isatin and its derivatives with 2-[(2,6-dichlorophenyl)amino]phenylacetic acid. ARKIVOC, 2007, 14, 51-57.
[65]
Patel, A.; Bari, S.; Telele, G.; Patel, J. Sarangapani. M. Synthesis and Antimicrobial Activity of Some New Isatin Derivatives. Iran. J. Pharm. Sci, 2006, 4, 249-254.
[66]
Sridhar, S.K.; Saravanan, M.; Ramesh, A. Synthesis and antibacterial screening of hydrazones, Schiff and Mannich bases of isatin derivatives. Eur. J. Med. Chem., 2001, 36(7-8), 615-625.
[http://dx.doi.org/10.1016/S0223-5234(01)01255-7] [PMID: 11600231]
[67]
Motzer, R.J.; Michaelson, M.D.; Redman, B.G.; Hudes, G.R.; Wilding, G.; Figlin, R.A.; Ginsberg, M.S.; Kim, S.T.; Baum, C.M.; DePrimo, S.E.; Li, J.Z.; Bello, C.L.; Theuer, C.P.; George, D.J.; Rini, B.I. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J. Clin. Oncol., 2006, 24(1), 16-24.
[http://dx.doi.org/10.1200/JCO.2005.02.2574] [PMID: 16330672]
[68]
Prenen, H.; Cools, J.; Mentens, N.; Folens, C.; Sciot, R.; Schöffski, P.; Van Oosterom, A.; Marynen, P.; Debiec-Rychter, M. Efficacy of the kinase inhibitor SU11248 against gastrointestinal stromal tumor mutants refractory to imatinib mesylate. Clin. Cancer Res., 2006, 12(8), 2622-2627.
[http://dx.doi.org/10.1158/1078-0432.CCR-05-2275] [PMID: 16638875]
[69]
Griffith, R.; Brown, M.N.; McCluskey, A.; Ashman, L.K. Small molecule inhibitors of protein kinases in cancer- how to overcome resistance. Mini Rev. Med. Chem., 2006, 6(10), 1101-1110.
[http://dx.doi.org/10.2174/138955706778560184] [PMID: 17073710]
[70]
Klenke, F.M.; Abdollahi, A.; Bertl, E.; Gebhard, M.M.; Ewerbeck, V.; Huber, P.E.; Sckell, A. Tyrosine kinase inhibitor SU6668 represses chondrosarcoma growth via antiangiogenesis in vivo. BMC Cancer, 2007, 7, 49.
[http://dx.doi.org/10.1186/1471-2407-7-49] [PMID: 17367541]
[71]
Nguyen, J.T.; Wells, J.A. Direct activation of the apoptosis machinery as a mechanism to target cancer cells. Proc. Natl. Acad. Sci. USA, 2003, 100(13), 7533-7538.
[http://dx.doi.org/10.1073/pnas.1031631100] [PMID: 12808146]
[72]
Progress in drug research potterat, O.; Hamburger, M.; Birkhaeuser, Eds.; In: Natural Compounds as Drugs; , 2008; pp. 62-64.
[73]
Zhang, X.; Song, Y.; Wu, Y.; Dong, Y.; Lai, L.; Zhang, J.; Lu, B.; Dai, F.; He, L.; Liu, M.; Yi, Z. Indirubin inhibits tumor growth by antitumor angiogenesis via blocking VEGFR2-mediated JAK/STAT3 signaling in endothelial cell. Int. J. Cancer, 2011, 129(10), 2502-2511.
[http://dx.doi.org/10.1002/ijc.25909] [PMID: 21207415]
[74]
Jiang, T.; Kuhen, K.L.; Wolff, K.; Yin, H.; Bieza, K.; Caldwell, J.; Bursulaya, B.; Wu, T.Y.H.; He, Y. Design, synthesis and biological evaluations of novel oxindoles as HIV-1 non-nucleoside reverse transcriptase inhibitors. Part I. Bioorg. Med. Chem. Lett., 2006, 16(8), 2105-2108.
[http://dx.doi.org/10.1016/j.bmcl.2006.01.073] [PMID: 16480865]
[75]
Mohammad, M. Mahon, Mc.; Sun, L.; Tabg, C.; Hirth, P.; Yeh, B. K.; Hubbard, S.R. Schlessinger, structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors. J. Sci., 1997, 276, 955.
[76]
Levitzki, A.; Gazit, A. Tyrosine kinase inhibition: An approach to drug development. Science, 1995, 267(5205), 1782-1788.
[http://dx.doi.org/10.1126/science.7892601] [PMID: 7892601]
[77]
Sun, L.; Tran, N.; Tang, F.; App, H.; Hirth, P.; McMahon, G.; Tang, C. Synthesis and biological evaluations of 3-substituted indolin-2-ones: a novel class of tyrosine kinase inhibitors that exhibit selectivity toward particular receptor tyrosine kinases. J. Med. Chem., 1998, 41(14), 2588-2603.
[http://dx.doi.org/10.1021/jm980123i] [PMID: 9651163]
[78]
Sun, L.; Liang, C.; Shirazian, S.; Zhou, Y.; Miller, T.; Cui, J.; Fukuda, J.Y.; Chu, J.Y.; Nematalla, A.; Wang, X.; Chen, H.; Sistla, A.; Luu, T.C.; Tang, F.; Wei, J.; Tang, C. Discovery of 5-[5-fluoro-2-oxo-1,2- dihydroindol-(3Z)-ylidenemethyl]-2,4- dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel tyrosine kinase inhibitor targeting vascular endothelial and platelet-derived growth factor receptor tyrosine kinase. J. Med. Chem., 2003, 46(7), 1116-1119.
[http://dx.doi.org/10.1021/jm0204183] [PMID: 12646019]
[79]
Musajo, L.; Marzolo, V. Treating hyperlipemia with isatin, 3803319, 09 Apr 1974.
[80]
Gassman, P.G.; Cue, B.W. Isatin products, 4186132, 29 Jan, 1980.
[81]
Gassman, P.G.; Cue, B.W. Isatin process and products, US, 1980 12 Feb; 4, 188-325.
[82]
Kobayashi, V.; Kitazawa, M.; Akahane, M.; Tsukamoto, T.; Yamamoto, R.; Nakano, Y. Isatin compositions having anti-ulcer activities, 4780477, Oct 25, 1988.
[83]
Jensen, B. S.; Jorgensen, T. D.; Ahring, P. K.; Christophersen, P.; Strobaek, D.; Teuber, L.; Olesen, S. P. Use of isatin derivatives as ion channel activating agents. Feb 7, 2002. US 20020016354 A1
[84]
Yang, H. Use of isatin in stimulating red blood cell production and treatment of anemia. Oct 12, 2006. US 20060229354 A1.
[85]
Kester, R.F. Isatin and oxindole compounds June 07 2012. US 20120142705 A1
[86]
Mach, R.H.; Welch, M.; Chu, W.; Rothfuss, J. Isatin analogues and uses therefore Dec 11, 2012. US 8329686 B2
[87]
Mohamed Hassan, T.A.F.; Kadi, A.A.; Abdel-Aziz, H.A.K. N N'-hydrazinobis-isatin derivatives with selective activity against multidrugresistant cancer cells, Jul 30, 2013. US 8497296 B2.
[88]
Mohamed Hassan, T.A.F.; Ahmad, S. Isatin derivatives, medicaments containing the satin derivatives and method for its preparation Oct 08, 2013. US 8552026 B2.
[89]
Wu, J.; Lawrence, N. J.; Sebti, S. M.; Lawrence, H. R. Carboxy isatinhydrazones and their esters as SHP2 inhibitors Jan 07, 2014. US 8623906 B2.
[90]
Beeson, C.C.; Lindsey, C.C.; Peterson, Y.K.; Rohrer, B. Isatin compounds, compositions and methods for treatment of degenerative diseases and disorders Jul 14 2015. US 9079853 B2.
[91]
Aboagye, E.O.; Smith, G.; Nguyen, Q. De, Isatin derivatives for use as in vivo imaging agents, Feb 24, 2015. US 8961930 B2.
[92]
Horne, D.A.; Jove, R. Isatin derivatives, pharmaceutical compositions thereof, and methods of use thereof Nov 28 2017. US 9828342 B2.
[93]
Liang, C.; Jia, M.; Tian, D.; Wang, X.; Chen, X.; Li, J.; Tong, G. Asymmetric 7 - n isatin dimer schiff base compounds with antitumor activities and a method of preparing the same, Sep 05, 2017. US 9751896 B1.
[94]
Liang, C.; Tian, D.; Jia, M. Isatin peroxo compounds with antibacterial activities and a method of preparing the same Jul 31 2018. US 10035808 B1.
[95]
Beeson, C. C.; Lindsey, C. C.; Peterson, Y. K.; Rohrer, B. Isatin compounds compositions and methods for treatment of degenerative diseases and disorders Mar 20 2018. US 9 920029 B2.
[96]
Liang, C.; Tian, D.; Ding, S. Isatinspiro compounds with antibacterial activities and a method of preparing the same Sep 11 2018. US 10072020 B1.
[97]
YU, P.; Wang, D.; Teng, Y.; Miao, L.; Wang, J.; Zhang, Q. Yuan, Y.. Water soluble isatin derivative and manufacturing method and application thereof, Nov 28, 2019. US 20190359568 A1.
[98]
Boechat, N.; Bactos, M. M.; Lopes, E; Souza, T. M.; Leite, D. I.; Bernardino, M. R. Isatin derived compounds, use of the compounds for the treatment of aids and method of treatment using these compounds Jan 21 2020. US 10538515 B2.
[99]
Pandeya, S.N.; Sriram, D.; Yogeeswari, P.; Ananthan, S. Antituberculous activity of norfloxacin mannich bases with isatin derivatives. Chemotherapy, 2001, 47(4), 266-269.
[http://dx.doi.org/10.1159/000048533] [PMID: 11399863]
[100]
Aboul-Fadl, T.; Mohammed, F.A.H.; Hassan, E.A.S. Synthesis, antitubercular activity and pharmacokinetic studies of some Schiff bases derived from 1-alkylisatin and isonicotinic acid hydrazide (INH). Arch. Pharm. Res., 2003, 26(10), 778-784.
[http://dx.doi.org/10.1007/BF02980020] [PMID: 14609123]
[101]
Aboul-Fadl, T.; Bin-Jubair, F.A.S.; Aboul-Wafa, O. Schiff bases of indoline-2,3-dione (isatin) derivatives and nalidixic acid carbohydrazide, synthesis, antitubercular activity and pharmacophoric model building. Eur. J. Med. Chem., 2010, 45(10), 4578-4586.
[http://dx.doi.org/10.1016/j.ejmech.2010.07.020] [PMID: 20696500]
[102]
Raja, S.; Prakash, C.R. Novel 1-(4-substituted benzylidene)-4-(1-(substituted methyl)-2,3-dioxoindolin-5-yl)semicarbazide derivatives for use against Mycobacterium tuberculosis H37Rv (ATCC 27294) and MDR-TB strain. Arch. Pharm. Res., 2013, 36(4), 411-422.
[http://dx.doi.org/10.1007/s12272-013-0062-1] [PMID: 23440582]
[103]
Yurttas, L. Ertas, Cankiliç, M. M. Y.; Demirayak, S. Synthesis and Antimycobacterial Activity Evaluation of Isatin-derived 3- [(4- aryl - 2-thiazolyl])hydrazone]-1H- indol- 2, 3- diones. Acta Pharm. Sci., 2017, 55, 51-58.
[104]
Xu, Y.; Dang, R.; Guan, J.; Xu, Z.; Zhao, S.; Hu, Y. Isatin-(thio)semicarbazide/oxime-1H-1,2,3-triazole-coumarin Hybrids: Design, Synthesis, and in vitro Anti-mycobacterial Evaluation. J. Heterocycl. Chem., 2018, 55, 1069-1073.
[http://dx.doi.org/10.1002/jhet.3104]
[105]
Gao, F.; Yang, H.; Lu, T.; Chen, Z.; Ma, L.; Xu, Z.; Schaffer, P.; Lu, G. Design, synthesis and anti-mycobacterial activity evaluation of benzofuran-isatin hybrids. Eur. J. Med. Chem., 2018, 159, 277-281.
[http://dx.doi.org/10.1016/j.ejmech.2018.09.049] [PMID: 30296686]
[106]
Xu, Y.; Guan, J.; Xu, Z.; Zhao, S. Design, synthesis and in vitro anti-mycobacterial activities of homonuclear and heteronuclear bis-isatin derivatives. Fitoterapia, 2018, 127, 383-386.
[http://dx.doi.org/10.1016/j.fitote.2018.03.018] [PMID: 29631015]
[107]
Yan, X.; Lv, Z.; Wen, J.; Zhao, S.; Xu, Z. Design, synthesis and in vitro anti-mycobacterial activities of homonuclear and heteronuclear bis-isatin derivatives. Eur. J. Med. Chem., 2018, 143, 899-904.
[http://dx.doi.org/10.1016/j.ejmech.2017.11.090] [PMID: 29227930]
[108]
Xu, Z.; Zhang, S.; Song, X.; Qiang, M.; Lv, Z. Design, synthesis and in vitro anti-mycobacterial evaluation of gatifloxacin-1H-1,2,3-triazole-isatin hybrids. Bioorg. Med. Chem. Lett., 2017, 27(16), 3643-3646.
[http://dx.doi.org/10.1016/j.bmcl.2017.07.023] [PMID: 28720502]
[109]
Hu, Y.Q.; Xu, Z.; Qiang, Z.M.; Lv, Z.S. Design, Synthesis and in vitro Antimycobacterial Activities of Isatin-1,2,3-triazole-moxif loxacin Hybrids. J. Heterocycl. Chem., 2018, 55, 187-191.
[http://dx.doi.org/10.1002/jhet.3023]
[110]
Xu, Z.; Zhao, S.J.; Deng, J.L.; Wang, Q.; Sheng, Z. Design, Synthesis, and Antimycobacterial Activities of Diethylene Glycol Tethered Moxifloxacin–Isatin Hybrids. J. Heterocycl. Chem., 2019, 56, 325-330.
[http://dx.doi.org/10.1002/jhet.3383]
[111]
Solomon, V.R.; Hu, C.; Lee, H. Hybrid pharmacophore design and synthesis of isatin-benzothiazole analogs for their anti-breast cancer activity. Bioorg. Med. Chem., 2009, 17(21), 7585-7592.
[http://dx.doi.org/10.1016/j.bmc.2009.08.068] [PMID: 19804979]
[112]
Ramshid, P.K.; Jagadeeshan, S.; Krishnan, A.; Mathew, M.; Nair, S.A.; Pillai, M.R. Synthesis and in vitro evaluation of some isatin-thiazolidinone hybrid analogues as anti-proliferative agents. Med. Chem., 2010, 6(5), 306-312.
[http://dx.doi.org/10.2174/157340610793358909] [PMID: 21073435]
[113]
Gudipati, R.; Anreddy, R.N.R.; Manda, S. Synthesis, anticancer and antioxidant activities of some novel N-(benzo[d]oxazol-2-yl)-2-(7- or 5-substituted-2-oxoindolin-3-ylidene) hydrazinecarboxamide derivatives. J. Enzyme Inhib. Med. Chem., 2011, 26(6), 813-818.
[http://dx.doi.org/10.3109/14756366.2011.556630] [PMID: 21476831]
[114]
Modi, N.R.; Shah, R.J.; Patel, M.J.; Suthar, M.; Chauhan, B.F.; Patel, L. Design, synthesis, and QSAR study of novel 2-(2,3-dioxo-2,3-dihydro-1H-indol-1-yl)-N-phenylacetamide derivatives as cytotoxic agents. J. Med Chem Res., 2011, 20, 615-625.
[http://dx.doi.org/10.1007/s00044-010-9361-y]
[115]
Taher, A.T.; Khalil, N.A.; Ahmed, E.M. Synthesis of novel isatin-thiazoline and isatin-benzimidazole conjugates as anti-breast cancer agents. Arch. Pharm. Res., 2011, 34(10), 1615-1621.
[http://dx.doi.org/10.1007/s12272-011-1005-3] [PMID: 22076761]
[116]
Singh, P.; Kaur, S.; Kumar, V.; Bedi, P.M.S.; Mahajan, M.P.; Sehar, I.; Pal, H.C.; Saxena, A.K. Synthesis and in vitro cytotoxic evaluation of N-alkylbromo and N-alkylphthalimido-isatins. Bioorg. Med. Chem. Lett., 2011, 21(10), 3017-3020.
[http://dx.doi.org/10.1016/j.bmcl.2011.03.043] [PMID: 21482109]
[117]
Singh, P.; Sharma, P.; Anand, A.; Bedi, P.M.S.; Kaur, T.; Saxena, A.K.; Kumar, V. Azide-alkyne cycloaddition en route to novel 1H-1,2,3-triazole tethered isatin conjugates with in vitro cytotoxic evaluation. Eur. J. Med. Chem., 2012, 55, 455-461.
[http://dx.doi.org/10.1016/j.ejmech.2012.06.057] [PMID: 22818042]
[118]
Karthikeyan, C.; Solomon, V.R.; Lee, H.; Trivedi, P. Design, synthesis and biological evaluation of some isatin-linked chalcones asnovel anti-breast cancer agents: A molecular hybridization approach. Biomed Prev Nutr., 2013, 3, 325-330.
[http://dx.doi.org/10.1016/j.bionut.2013.04.001]
[119]
Liu, H.Q.; Wang, D.C.; Wu, F.; Tang, W.; Ouyang, P.K. Synthesis and biological evaluation of 50-phenyl-30H-spiro- [indoline-3,20-[1,3,4]oxadiazol]-2-one analogs. Chin. Chem. Lett., 2013, 24, 929-933.
[http://dx.doi.org/10.1016/j.cclet.2013.06.001]
[120]
Yang, Y.; Song, B.; Han, K.; Zhang, Li.; Wu, D.; Qu, X.; Li, H.; Sun, H.; Teng, Y.; Yu, P. Design, synthesis and biological evaluation of N-phenyl substituted isatin derivatives. J. Chem. Pharm. Res., 2014, 6, 140-145.
[121]
Han, K.; Zhou, Y.; Liu, F.; Guo, Q.; Wang, P.; Yang, Y.; Song, B.; Liu, W.; Yao, Q.; Teng, Y.; Yu, P. Design, synthesis and in vitro cytotoxicity evaluation of 5-(2-carboxyethenyl)isatin derivatives as anticancer agents. Bioorg. Med. Chem. Lett., 2014, 24(2), 591-594.
[http://dx.doi.org/10.1016/j.bmcl.2013.12.001] [PMID: 24360564]
[122]
Dweedar, H.E.; Mahrous, H.; Ibrahim, H.S.; Abdel-Aziz, H.A. Analogue-based design, synthesis and biological evaluation of 3-substituted-(methylenehydrazono)indolin-2-ones as anticancer agents. Eur. J. Med. Chem., 2014, 78, 275-280.
[http://dx.doi.org/10.1016/j.ejmech.2014.03.058] [PMID: 24686014]
[123]
Katiyar, A.; Hegde, M.; Kumar, S.; Gopalakrishnan, V.; Bhatelia, K.D.; Ananthaswamy, K.; Ramareddy, S.A.; Clercq, E.D.; Choudhary, B.; Schols, D.; Raghavan, S.C.; Karki, S.S. Synthesis and evaluation of the biological activity of N′-[2-oxo-1,2 dihydro-3H-indol-3-ylidene] benzohydrazides aspotential anticancer agents. RSC Advances, 2015, 5, 45492-45501.
[http://dx.doi.org/10.1039/C5RA01528F]
[124]
Ke, S.; Shi, L.; Yang, Z. Discovery of novel isatin-dehydroepiandrosterone conjugates as potential anticancer agents. Bioorg. Med. Chem. Lett., 2015, 25(20), 4628-4631.
[http://dx.doi.org/10.1016/j.bmcl.2015.08.041] [PMID: 26320625]
[125]
Sharma, S.; Gupta, M.K.; Saxena, A.K.; Bedi, P.M. Triazole linked mono carbonyl curcumin-isatin bifunctional hybrids as novel anti tubulin agents: Design, synthesis, biological evaluation and molecular modeling studies. Bioorg. Med. Chem., 2015, 23(22), 7165-7180.
[http://dx.doi.org/10.1016/j.bmc.2015.10.013] [PMID: 26515041]
[126]
Yu, B.; Wang, S.Q.; Qi, P.P.; Yang, D.X.; Tang, K.; Liu, H.M. Design and synthesis of isatin/triazole conjugates that induce apoptosis and inhibit migration of MGC-803 cells. Eur. J. Med. Chem., 2016, 124, 350-360.
[http://dx.doi.org/10.1016/j.ejmech.2016.08.065] [PMID: 27597411]
[127]
Babu, R.R.; Radhika, T.; Tejaswini, B. Reddy, Babu. V. H. Synthesis, characterization, anti-cancer and anti-bacterial study of isatin conjugated 4-azidopyrazoline derivatives. Pharma Chem., 2016, 8, 411-418.
[128]
Eldehna, W.M.; Fares, M.; Ibrahim, H.S.; Alsherbiny, M.A.; Aly, M.H.; Ghabbour, H.A.; Abdel-Aziz, H.A. Synthesis and Cytotoxic Activity of Biphenylurea Derivatives Containing Indolin-2-one Moieties. Molecules, 2016, 21(6), 762.
[http://dx.doi.org/10.3390/molecules21060762] [PMID: 27294903]
[129]
Kumar, N.; Sharma, C.S.; Singh, H.P.; Chauhan, L.S. Synthesis and in vitro evaluation of novel isatinincorporated thiadiazole hybrids as potential anti-breast cancer agents. Trop. J. Pharm. Res., 2017, 16, 1957-1963.
[130]
El-Azab, A.S.; Al-Dhfyan, A.; Abdel-Aziz, A.A.M.; Abou-Zeid, L.A.; Alkahtani, H.M.; Al-Obaid, A.M.; Al-Gendy, M.A. Synthesis, anticancer and apoptosis-inducing activities of quinazoline-isatin conjugates: epidermal growth factor receptor-tyrosine kinase assay and molecular docking studies. J. Enzyme Inhib. Med. Chem., 2017, 32(1), 935-944.
[http://dx.doi.org/10.1080/14756366.2017.1344981] [PMID: 28718672]
[131]
Eldehna, W.M.; Almahli, H.; Al-Ansary, G.H.; Ghabbour, H.A.; Aly, M.H.; Ismael, O.E.; Al-Dhfyan, A.; Abdel-Aziz, H.A. Synthesis and in vitro anti-proliferative activity of some novel isatins conjugated with quinazoline/phthalazine hydrazines against triple-negative breast cancer MDA-MB-231 cells as apoptosis-inducing agents. J. Enzyme Inhib. Med. Chem., 2017, 32(1), 600-613.
[http://dx.doi.org/10.1080/14756366.2017.1279155] [PMID: 28173708]
[132]
Gangarap, K.; Thumma, G.; Manda, S.; Jallapally, A.; Jarapula, R.; Rekulapally, S. Design, synthesis and molecular docking of novel structural hybrids of substituted isatin based pyrazoline and thiadiazoline as antitumor agents. Med. Chem. Res., 2017, 26, 819-829.
[http://dx.doi.org/10.1007/s00044-017-1781-5]
[133]
Singh, H.; Singh, J.V.; Gupta, M.K.; Saxena, A.K.; Sharma, S.; Nepali, K.; Bedi, P.M.S. Triazole tethered isatin-coumarin based molecular hybrids as novel antitubulin agents: Design, synthesis, biological investigation and docking studies. Bioorg. Med. Chem. Lett., 2017, 27(17), 3974-3979.
[http://dx.doi.org/10.1016/j.bmcl.2017.07.069] [PMID: 28797799]
[134]
Panga, S.; Podila, N.K.; Ciddi, V. Design, Synthesis, Characterization, and In Vitro Evaluation of Isatin-Pomalidomide Hybrids for Cytotoxicity against Multiple Myeloma Cell Lines. J. Heterocycl. Chem., 2018, 55, 2919-2928.
[http://dx.doi.org/10.1002/jhet.3365]
[135]
Meleddu, R.; Petrikaite, V.; Distinto, S.; Arridu, A.; Angius, R.; Serusi, L.; Škarnulytė, L.; Endriulaitytė, U.; Paškevičiu Tė, M.; Cottiglia, F.; Gaspari, M.; Taverna, D.; Deplano, S.; Fois, B.; Maccioni, E. Investigating the Anticancer Activity of Isatin/Dihydropyrazole Hybrids. ACS Med. Chem. Lett., 2018, 10(4), 571-576.
[http://dx.doi.org/10.1021/acsmedchemlett.8b00596] [PMID: 30996798]
[136]
El-Naggar, M.; Eldehna, W.M.; Almahli, H.; Elgez, A.; Fares, M.; Elaasser, M.M.; Abdel-Aziz, H.A. Novel Thiazolidinone/Thiazolo[3,2-a]Benzimidazolone-Isatin Conjugates as Apoptotic Anti-proliferative Agents Towards Breast Cancer: One-Pot Synthesis and in vitro Biological Evaluation. Molecules, 2018, 23(6), 1420.
[http://dx.doi.org/10.3390/molecules23061420] [PMID: 29895744]
[137]
Singh, U.K.; Pandeya, S.N.; Singh, A.; Srivastava, B.K.; Pandey, M. Synthesis and Antimicrobial Activity of Schiff’s and N-Mannich Bases of Isatin and Its Derivatives with 4-Amino-N-Carbamimidoyl Benzene Sulfonamide. Int. J. Pharm. Sci. Drug Res., 2010, 2, 151-154.
[138]
Ugale, V.; Patel, H.; Patel, B.; Bari, S. Benzofurano-isatins: Search for antimicrobial agents. Arab. J. Chem., 2012, 10, S389-S396.
[http://dx.doi.org/10.1016/j.arabjc.2012.09.011]
[139]
Shah, R.J.; Modi, N.R.; Patel, M.J.; Patel, L.J.; Chauhan, B.F.; Patel, M.M. Design, synthesis and in vitro antibacterial and antifungal activities of some novel spiro[azetidine-2,30-indole]-2,4(10H)-dione. Med. Chem. Res., 2011, 20, 587-594.
[http://dx.doi.org/10.1007/s00044-010-9354-x]
[140]
Marvel, C.S.; Hiers, G.S. Isatin. Org Synth Coll., 1941, 1, 327.
[141]
Vine, K.L.; Locke, J.M.; Ranson, M.; Benkendorff, K.; Pyne, S.G.; Bremner, J.B. In vitro cytotoxicity evaluation of some substituted isatin derivatives. Bioorg. Med. Chem., 2007, 15(2), 931-938.
[http://dx.doi.org/10.1016/j.bmc.2006.10.035] [PMID: 17088067]
[142]
Holton, R.A.; Liu, J.H. A novel asymmetric synthesis of cis-3-hydroxy-4-aryl azetidin-2-ones. Bioorg. Med. Chem. Lett., 1993, 3, 2475-2478.
[http://dx.doi.org/10.1016/S0960-894X(01)80981-1]
[143]
Wang, R.; Yin, X.; Zhang, Y.; Yan, W. Design, synthesis and antimicrobial evaluation of propylene-tethered ciprofloxacin-isatin hybrids. Eur. J. Med. Chem., 2018, 156, 580-586.
[http://dx.doi.org/10.1016/j.ejmech.2018.07.025] [PMID: 30025351]
[144]
Jabbar, S.S. synthesis, characterization and antibacterial activity of carbamate derivatives of isatin. Orient. J. Chem., 2018, 34, 2026-2030.
[http://dx.doi.org/10.13005/ojc/3404041]
[145]
Akhaja, T.N.; Raval, J.P. Design, synthesis, in vitro evaluation of tetrahydropyrimidine–isatin hybrids as potential antibacterial, antifungal and anti-tubercular agents. Chin. Chem. Lett., 2012, 23, 446-449.
[http://dx.doi.org/10.1016/j.cclet.2012.01.040]
[146]
Al-Wabli, R.I.; Zakaria, A.S.; Attia, M.I. Synthesis, spectroscopic characterization andantimicrobial potential of certain new isatin-indole molecular hybrids. Molecules, 2017, 22, 1958.
[http://dx.doi.org/10.3390/molecules22111958]
[147]
Guo, H. Design, Synthesis, and in vitro antibacterial activities of propylenetethered gatifloxacin-isatin hybrids J. Heterocyclic Chem., 2018, 55, 1899-1905.
[http://dx.doi.org/10.1002/jhet.3226]
[148]
Panneerselvam, P.; Reddy, R.S.; Murali, K.; Kumar, N.R. Synthesis, analgesic, anti-inflammatory and antimicrobial activities of some novel Schiff’s bases of 5-subsituted Isatin. Pharma Chem., 2010, 2, 28-37.
[149]
Srinivas, B.; Priya, V.R.; Babu, G.S.; Rao, J.V.; Malathy, P.S.; Manohar, K.R.; Prakash, B.C.; Srikanth, L. Synthesis and screening of new isatin derivatives. Pharma Chem., 2010, 2, 378-384.
[150]
Maddela, S.; Makula, A.; Maddela, R. Synthesis of isatin–quinoline conjugates as possible biologically active agents. Toxicol. Environ. Chem., 2014, 96, 1-11.
[http://dx.doi.org/10.1080/02772248.2014.918464]
[151]
Sharma, P.K.; Balwani, S.; Mathur, D.; Malhotra, S.; Singh, B.K.; Prasad, A.K.; Len, C.; Van der Eycken, E.V.; Ghosh, B.; Richards, N.G.J.; Parmar, V.S. Synthesis and anti-inflammatory activity evaluation of novel triazolyl-isatin hybrids. J. Enzyme Inhib. Med. Chem., 2016, 31(6), 1520-1526.
[http://dx.doi.org/10.3109/14756366.2016.1151015] [PMID: 27146339]
[152]
Kumar, S.; Bains, T.; Won Kim, A.S.; Tam, C.; Kim, J.; Cheng, L.W.; Land, K.M.; Debnath, A.; Kumar, V. Highly potent 1H-1,2,3-triazole-tethered isatin-metronidazole conjugates against anaerobic foodborne, waterborne, and sexually-transmitted protozoal parasites. Front. Cell. Infect. Microbiol., 2018, 8, 380.
[http://dx.doi.org/10.3389/fcimb.2018.00380] [PMID: 30425970]
[153]
Devale, T.L.; Parikh, J.; Miniyar, P.; Sharma, P.; Shrivastava, B.; Murumkar, P. Dihydropyrimidinone-isatin hybrids as novel non-nucleoside HIV-1 reverse transcriptase inhibitors. Bioorg. Chem., 2017, 70, 256-266.
[http://dx.doi.org/10.1016/j.bioorg.2017.01.006] [PMID: 28160944]
[154]
Kumar, K.; Liu, N.; Yang, D.; Na, D.; Thompson, J.; Wrischnik, L.A.; Land, K.M.; Kumar, V. Synthesis and antiprotozoal activity of mono- and bis-uracil isatin conjugates against the human pathogen Trichomonas vaginalis. Bioorg. Med. Chem., 2015, 23(16), 5190-5197.
[http://dx.doi.org/10.1016/j.bmc.2015.04.075] [PMID: 25999204]
[155]
Chen, L.R.; Wang, Y.C.; Lin, Y.W.; Chou, S.Y.S.; Chen, S.F.; Liu, L.T.; Wu, Y.T.; Kuo, C.J.; Chen, T.S.; Juang, S.H. Synthesis and evaluation of isatin derivatives as effective SARS coronavirus 3CL protease inhibitors. Bioorg. Med. Chem. Lett., 2005, 15(12), 3058-3062.
[http://dx.doi.org/10.1016/j.bmcl.2005.04.027] [PMID: 15896959]
[156]
Zhou, L.; Liu, Y.; Zhang, W.; Wei, P.; Huang, C.; Pei, J.; Yuan, Y.; Lai, L. Isatin compounds as noncovalent SARS coronavirus 3C-like protease inhibitors. J. Med. Chem., 2006, 49(12), 3440-3443.
[http://dx.doi.org/10.1021/jm0602357] [PMID: 16759084]
[157]
Saravanan, G.; Alagarsamy, V.; Dineshkumar, P. Anticonvulsant activity of novel 1-(morpholinomethyl)-3-substituted isatin derivatives. Bull Fac Phar., 2014, 52, 115-124.
[http://dx.doi.org/10.1016/j.bfopcu.2014.02.001]
[158]
Kumar, R.; Singh, T.; Singh, H.; Jain, S.; Roy, R.K. 1H-1,2,3-triazole tethered isatin-ferrocene conjugates: Synthesis and in vitro antimalarial evaluation. EXCLI J., 2014, 13, 225-240.
[http://dx.doi.org/10.1016/j.ejmech.2014.10.024] [PMID: 26417257]
[159]
Pervez, H.; Manzoor, N.; Yaqub, M.; Khan, K.M. 5-Nitroisatin-derived thiosemicarbazones: potential antileishmanial agents. J. Enzyme Inhib. Med. Chem., 2014, 29(5), 628-632.
[http://dx.doi.org/10.3109/14756366.2013.836641] [PMID: 24090424]
[160]
Raj, R.; Singh, P.; Singh, P.; Gut, J.; Rosenthal, P.J.; Kumar, V. Azide-alkyne cycloaddition en route to 1H-1,2,3-triazole-tethered 7-chloroquinoline-isatin chimeras: synthesis and antimalarial evaluation. Eur. J. Med. Chem., 2013, 62, 590-596.
[http://dx.doi.org/10.1016/j.ejmech.2013.01.032] [PMID: 23434528]

Rights & Permissions Print Cite
Article Metrics
96
© 2024 Bentham Science Publishers | Privacy Policy