Abstract

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.

Keywords: Quinoxaline, triazolo[4, 3-a]quinoxaline, aldehydo-sugar hydrazone, acyclic C-nucleoside, antioxidant, anticancer, antiviral activities.

Graphical Abstract