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Mini-Reviews in Organic Chemistry


ISSN (Print): 1570-193X
ISSN (Online): 1875-6298

Mini-Review Article

Alkaloids as Antimalarial Compounds: A Review of Recent Studies

Author(s): Nor Asma Umais Mohammad Saufi, Ummu Umairah M. Hatta, Fatin Nur Ain Abdul Rashid and Mohd Fazli Mohammat*

Volume 20, Issue 8, 2023

Published on: 16 November, 2022

Page: [786 - 799] Pages: 14

DOI: 10.2174/1570193X20666221018090845

Price: $65


Malaria is a parasitic infection caused by Plasmodium parasites that are transmitted to humans through the bite of infected Anopheles mosquitoes. Malaria continues to contribute unacceptably high rates of sickness and death. Natural product compounds have long been recognized as one of valuable natural remedy resources with promising structural motif pools for the development of first-line drugs. Resistance to conventional treatments such as chloroquine, mefloquine, and artemisinin- based combination therapy (ACT) by the causal agent, the Plasmodium parasite, is a major concern in malaria treatment and prevention globally. Given the parasites' resistance to several current treatment regimens, innovative antimalarial chemotherapeutic medicines derived from tetramic acid alkaloids are desperately needed. In this review, new and old antimalarial alkaloids identified and reported recently from 2017 to 2021 are presented. Several compounds with promising antimalarial activity are identified from several subclasses of alkaloids. It is hoped that this review report will inspire future research into the compounds' toxicity and in vivo efficacy, to exploit this intriguing compound as antimalarial drugs.

Keywords: Alkaloids, plant, malaria, Plasmodium falciparum, antimalarial, antiplasmodial activity.

Graphical Abstract
World Health Organization. World Malaria Report: 20 years of global progress and challenges. World Health Organization: Vol. WHO/HTM/GM. Available from: January 25, 2022).
WHO, Guideline WHO Guidelines for malaria. Available from: (Accessed February 16, 2021)
Tse, E.G.; Korsik, M.; Todd, M.H. The past, present and future of anti-malarial medicines. Malar. J., 2019, 18(1), 93.
[] [PMID: 30902052]
Ni, M.; He, J.G.; Zhou, H.Y.; Lu, X.J.; Hu, Y.L.; Mao, L.; Wang, F.; Chen, J.G.; Hu, Z.L. Pannexin-1 channel dysfunction in the medial prefrontal cortex mediates depressive-like behaviors induced by chronic social defeat stress and administration of mefloquine in mice. Neuropharmacology, 2018, 137, 256-267.
[] [PMID: 29221793]
Sharma, P.; McAlinden, K.D.; Ghavami, S.; Deshpande, D.A. Chloroquine: Autophagy inhibitor, antimalarial, bitter taste receptor agonist in fight against COVID-19, a reality check? Eur. J. Pharmacol., 2021, 897, 173928.
[] [PMID: 33545161]
Souza, K.A.F.D.; Porto, P.A. Porto, P. A. History, and epistemology of science in the classroom: The synthesis of quinine as a proposal. J. Chem. Educ., 2012, 89(1), 58-63.
Tripathi, M.; Taylor, D.; Khan, S.I.; Tekwani, B.L.; Ponnan, P.; Das, U.S.; Velpandian, T.; Rawat, D.S. Hybridization of fluoro-amodiaquine (FAQ) with pyrimidines: Synthesis and antimalarial efficacy of FAQ–pyrimidines. ACS Med. Chem. Lett., 2019, 10(5), 714-719.
[] [PMID: 31097988]
Bonilla-ramirez, L.; Rios, A.; Quiliano, M.; François, J.; Ramirez-calderon, G.; Corcuera, L.; Bordessoulles, M.; Vettorazzi, A.; Adela, L.; Aldana, I.; Mazier, D.; Pab, A. N-oxide hybrids: Design, synthesis, Plasmodium life cycle stage profile, and preliminary toxicity studies n Beltr a. Eur. J. Med. Chem., 2018, 158, 68-81.
[] [PMID: 30199706]
Dey, P.; Kundu, A.; Kumar, A.; Gupta, M.; Lee, B.M.; Bhakta, T.; Dash, S.; Kim, H.S. Analysis of alkaloids (indole alkaloids, isoquinoline alkaloids, tropane alkaloids).Recent Advances in Natural Products Analysis; Elsevier: Amsterdam, 2020, pp. 505-567.
Amelia, P.; Nugroho, A.E.; Hirasawa, Y.; Kaneda, T.; Tougan, T.; Horii, T.; Morita, H. Two new sarpagine-type indole alkaloids and antimalarial activity of 16-demethoxycarbonylvoacamine from Tabernaemontana macrocarpa Jack. J. Nat. Med., 2019, 73(4), 820-825.
[] [PMID: 31140017]
Amelia, P.; Nugroho, A.E.; Hirasawa, Y.; Kaneda, T.; Tougan, T.; Horii, T.; Morita, H. Two new bisindole alkaloids from Tabernaemontana macrocarpa Jack. J. Nat. Med., 2021, 75(3), 633-642.
[] [PMID: 33822287]
Robertson, L.P.; Lucantoni, L.; Avery, V.M.; Carroll, A.R. Antiplasmodial bis-indole alkaloids from the bark of flindersia pimenteliana. Planta Med., 2020, 86(1), 19-25.
[] [PMID: 31663109]
Tang, Y.; Nugroho, A.E.; Hirasawa, Y.; Tougan, T.; Horii, T.; Hadi, A.H.A.; Morita, H. Leucophyllinines A and B, bisindole alkaloids from Leuconotis eugeniifolia. J. Nat. Med., 2019, 73(3), 533-540.
[] [PMID: 30911994]
Robertson, L.P.; Duffy, S.; Wang, Y.; Wang, D.; Avery, V.M.; Carroll, A.R. Pimentelamines A–C, indole alkaloids isolated from the leaves of the Australian tree Flindersia pimenteliana. J. Nat. Prod., 2017, 80(12), 3211-3217.
[] [PMID: 29236492]
Bhatt, V.; Kumari, S.; Upadhyay, P.; Agrawal, P. Chemical profiling and quantification of p otential active constituents responsible for the antiplasmodial activity of Cissampelos pareira. J. Ethnopharmacol., 2020, 262(6), 113-185.
Uche, F.I.; Guo, X.; Okokon, J.; Ullah, I.; Horrocks, P.; Boateng, J.; Huang, C.; Li, W.W. In vivo efficacy and metabolism of the antimalarial cycleanine and improved in vitro antiplasmodial activity of semisynthetic analogues. Antimicrob. Agents Chemother., 2021, 65(2), e01995-e20.
[] [PMID: 33257443]
Abdel-Sattar, E.; Hossam, M.A.; Sahar, E.M. Chikara. I.; Hiroaki, K.; Haruki, Y. Antimalarial alkaloid from Hypoestes forskaolii. Exp. Parasitol., 2021, 211(6), 1-5.
Li, J.; Seupel, R.; Feineis, D.; Mudogo, V.; Kaiser, M.; Brun, R.; Brünnert, D.; Chatterjee, M.; Seo, E.J.; Efferth, T.; Bringmann, G. Dioncophyllines C2, D2, and F and related naphthylisoquinoline alkaloids from the congolese liana Ancistrocladus ileboensis with potent activities against Plasmodium falciparum and against multiple myeloma and leukemia cell lines. J. Nat. Prod., 2017, 80(2), 443-458.
[] [PMID: 28121440]
Moyo, P.; Shamburger, W.; van der Watt, M.E.; Reader, J.; de Sousa, A.C.C.; Egan, T.J.; Maharaj, V.J.; Bringmann, G.; Birkholtz, L.M. Naphthylisoquinoline alkaloids, validated as hit multistage antiplasmodial natural products. Int. J. Parasitol. Drugs Drug Resist., 2020, 13(5), 51-58.
[] [PMID: 32505117]
Tshitenge, D.T.; Feineis, D.; Mudogo, V.; Kaiser, M.; Brun, R.; Seo, E.J.; Efferth, T.; Bringmann, G. Mbandakamine-type naphthylisoquinoline dimers and related alkaloids from the central African liana ancistrocladus ealaensis with antiparasitic and antileukemic activities. J. Nat. Prod., 2018, 81(4), 918-933.
[] [PMID: 29560715]
Teng, W.C.; Chan, W.; Suwanarusk, R.; Ong, A.; Ho, H.K.; Russell, B.; Rénia, L.; Koh, H.L. In vitro antimalarial evaluations and cytotoxicity investigations of Carica papaya leaves and carpaine. Nat. Prod. Commun., 2019, 14(1), 1934578X1901400.
Kumar, R.; Duffy, S.; Avery, V.M.; Carroll, A.R.; Davis, R.A. Microthecaline A, a quinoline serrulatane alkaloid from the roots of the Australian desert plant Eremophila microtheca. J. Nat. Prod., 2018, 81(4), 1079-1083.
[] [PMID: 29533611]
Cheenpracha, S.; Boapun, P.; Limtharakul Née Ritthiwigrom, T.; Laphookhieo, S.; Pyne, S.G. Antimalarial and cytotoxic activities of pregnene-type steroidal alkaloids from Holarrhena pubescens roots. Nat. Prod. Res., 2019, 33(6), 782-788.
[] [PMID: 29172699]
Lang, L.; Hu, Q.; Wang, J.; Liu, Z.; Huang, J.; Lu, W.; Huang, Y. Coptisine, a natural alkaloid from Coptidis Rhizoma, inhibits plasmodium falciparum dihydroorotate dehydrogenase. Chem. Biol. Drug Des., 2018, 92(1), 1324-1332.
[] [PMID: 29582555]
Le, P.M.; Srivastava, V.; Nguyen, T.T.; Pradines, B.; Madamet, M.; Mosnier, J.; Trinh, T.T.; Lee, H. Stephanine from Stephania venosa (Blume) spreng showed effective antiplasmodial and anticancer activities, the latter by inducing apoptosis through the reverse of mitotic exit. Phytother. Res., 2017, 31(9), 1357-1368.
[] [PMID: 28703314]
Cho, N.; Du, Y.; Valenciano, A.L.; Fernández-Murga, M.L.; Goetz, M.; Clement, J.; Cassera, M.B.; Kingston, D.G.I. Antiplasmodial alkaloids from bulbs of Amaryllis belladonna Steud. Bioorg. Med. Chem. Lett., 2018, 28(1), 40-42.
[] [PMID: 29162457]
Gontijo, D.C.; Brandão, G.C.; Nascimento, M.F.A.; Braga de Oliveira, A. Antiplasmodial activity and cytotoxicity, isolation of active alkaloids, and dereplication of Xylopia sericea leaves ethanol extract by UPLC-DAD-ESI-MS/MS. J. Pharm. Pharmacol., 2019, 71(2), 260-269.
[] [PMID: 30303245]
Omar, H.; Fadaeinasab, M.; Taha, H.; Widyawaruyanti, A.; Nafiah, M.A.; Rachmatiah, T. Aporphine alkaloids with in vitro antiplasmodial activity from the leaves of Phoebe tavoyana. J. Asian Nat. Prod. Res., 2020, 22(1), 52-60.
[] [PMID: 30897964]
Zahari, A.; Cheah, F.; Mohamad, J.; Sulaiman, S.; Litaudon, M.; Leong, K.; Awang, K. Antiplasmodial and antioxidant isoquinoline alkaloids from Dehaasia longipedicellata. Planta Med., 2014, 80(7), 599-603.
[] [PMID: 24723007]

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