Abstract
C-glycosides are important class of molecules exhibit diverse biological activities and present as structural motif in many natural products. Two series of new pyrazoline and isoxazole bridged indole C-glycoside molecular hybrids (n = 36) were efficiently synthesized starting from diverse indole 3-carboxaldehydes derived α, β-unsaturated ketone derivatives of β-D-glucosyl-propan-2-one, β-D-galactosyl-propan-2-one and β-D-mannosyl-propan-2-one, reacting with hydrazine hydrate and hydroxyl amine hydrochloride in shorter reaction time (15 min) under microwave assisted condition. Anticancer activity of these newly synthesized pyrazoline and isoxazole bridged indoles C-glycoside hybrids were determined in details through cellular assays against MCF-7, MDA-MB-453 and MDA-MB-231 cancer cell lines. The selected library members displayed low micromolar (IC50 = 0.67–4.67 µM) and selective toxicity against breast cancer cell line (MCF-7). Whereas these compounds were nontoxic towards normal cell line (MCF-10A). Mechanistic studies showed that, active compounds inhibit COX-2 enzyme, which was also supported by molecular docking studies. These findings are expected to provide new leads towards anticancer drug discovery.
Highlights
C-glycosides are important class of molecules exhibit diverse biological activities and present as structural motif in many natural products
For the efficient synthesis of carbohydrate linked pyrazoline and isoxazole bridged C-glycoside of indole hybrids, we identified α, β-unsaturated-C-β glyosidic ketone molecule which can be synthesize by using C-glycoside 1–3 as substrate
Resulting α, β-unsaturated-C-β glyosidic ketone molecule can be coupled with hydrazine hydrate or hydroxyl amines at room temperature or elevated temperature conditions and get transformed to the designed pyrazoline or isoxazole bridged C-glycoside of indole through nucleophilic addition followed by dehydration reactions
Summary
C-glycosides are important class of molecules exhibit diverse biological activities and present as structural motif in many natural products. The purified C-glycosides based α, β-unsaturated ketone and their derivatives pyrazoline and isoxazole bridged indole C-glycoside hybrids have been screened for their anticancer activity against MCF-7, MDA-MB-453, MDA-MB-231 and MCF-10A. For the efficient synthesis of carbohydrate linked pyrazoline and isoxazole bridged C-glycoside of indole hybrids, we identified α, β-unsaturated-C-β glyosidic ketone molecule which can be synthesize by using C-glycoside 1–3 as substrate.
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