Synthesis, Antioxidant, Anticancer and Antiviral Activities of Novel Quinoxaline Hydrazone Derivatives and their Acyclic C-Nucleosides
Alaa A. El-Tombary and Soad A.M. El-Hawash
Pages 521-532 (12)
The present investigation describes the synthesis of a new series of aldehydo-sugar-N-(3-phenylquinoxalin-2-
yl)hydrazones 3a-d and their acyclic C-nucleoside analogs, 1-(4-phenyl-[1,2,4]triazolo[4,3-a]quinoxalin-1-yl)alditols 7ad
by using 2-hydrazino-3-phenylquinoxaline 1 as key intermediate. The synthesized compounds were screened for their
antioxidant activities by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation scavenging method.
Compounds 3d and 7a, showed potent scavenging activities against ABTS+ radicals and were found to be the most potent
antioxidants described in this study. Out of the synthesized compounds, compounds 3d and 7a were selected by the National
Cancer Institute for evaluation of their in vitro anticancer activity. Results revealed that compounds 3d and 7a exhibited
non-selective broad spectrum activity against all cancer cell lines between 10-6 to 10-5 molar concentrations. Compound
3d showed the highest sensitivity against leukemia cell line HL-60 (TB) with GI50 of 5.15 µM, while compound 7a
showed the highest sensitivity against ovarian cancer cell lines IGROV1 and OVCAR-4 with GI50 of 14.5 and 16.0 μM,
respectively. In addition, compounds 3d and 7a showed TGI values of 72.2 and 96.3 µM, respectively against ovarian
cancer cell line OVCAR-4. Furthermore, the target compounds were tested for antiviral activity against Herpes Simplex
virus type-1 (HSV-1) using plaque reduction infectivity assay. The results indicated that compounds 3a-d and 7a exhibited
very weak antiviral activity in comparison to Aphidicolin as a positive control.
Quinoxaline, triazolo[4, 3-a]quinoxaline, aldehydo-sugar hydrazone, acyclic C-nucleoside, antioxidant, anticancer,
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.