Design and efficient synthesis of pyrazoline and isoxazole bridged indole C-glycoside hybrids as potential anticancer agents.

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.

• Authors: Priti Kumari, Vishnu S Mishra, Chintam Narayana, Ashish Khanna, Anindita Chakrabarty, Ram Sagar
• Journal: Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 6660 (04 20 2020) ISSN: 2045-2322 [Electronic] England
• PMID: 32313038 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Cyclooxygenase 2 Inhibitors
• Glycosides
• Indoles
• Isoxazoles
• Pyrazoles
• Cyclooxygenase 2
• PTGS2 protein, human

Topics

• Antineoplastic Agents (chemical synthesis, pharmacology)
• Cell Line
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Chemistry Techniques, Synthetic
• Cyclooxygenase 2 (chemistry, metabolism)
• Cyclooxygenase 2 Inhibitors (chemical synthesis, pharmacology)
• Drug Design
• Drug Screening Assays, Antitumor
• Epithelial Cells (cytology, drug effects)
• Glycosides (chemical synthesis, pharmacology)
• Humans
• Indoles (chemical synthesis, pharmacology)
• Inhibitory Concentration 50
• Isoxazoles (chemical synthesis, pharmacology)
• MCF-7 Cells
• Microwaves
• Molecular Docking Simulation
• Organ Specificity
• Pyrazoles (chemical synthesis, pharmacology)
• Structure-Activity Relationship