Microwave-assisted one-pot efficient synthesis of functionalized 2-oxo-2-phenylethylidenes-linked 2-oxo-benzo[1,4]oxazines and 2-oxo-quino[1,4]oxalines: Synthetic Applications, Antioxidant activity, SAR and Cytotoxic Studies

Abstract

A microwave-assisted, environmentally benign green protocol for the synthesis of functionalized (Z)-3-(2-oxo-2-phenylethylidene)-3, 4-dihydro-2H-benzo[b][1,4]oxazin-2-ones 11a-n in excellent yields (upto 97%) and (Z)-3-(2-oxo-2-phenylethylidene)-3,4-dihydroquinoxalin-2(1H)-ones 14a-h (upto 96% yield) are reported. The practical applicability of developed methodology were also confirmed by the gram scale synthesis of 11a, 14c and 14e; synthesis of anticancer alkaloid Cephalandole A 16 (89% yield). All the synthesized compounds 11a-n, 14a-h and 16 were assessed for their in vitro antioxidant activities in DPPH radical scavenging and FRAP assay. In DPPH assay, compounds 11a, 14c and 14e, the most active compounds of the series, were found to show IC50 value of 10.20 ± 0.08 μg/mL, 9.89 ± 0.15 μg/mL and 8.97 ± 0.13 μg/mL, respectively in comparison with standard reference (ascorbic acid, IC50 = 4.57 μg/mL). Whereas, in FRAP antioxidant assay seven compounds (11c, 11e, 11i, 11k, 11l, 14d and 14h) displayed higher antioxidant activity comparison than reference standard BHT (C0.5FRAP = 546.2 μM). Moreover, the cytotoxic studies of the compounds 11a, 14c, 14e and 14h were found to be non-toxic in nature in 3T3 fibroblast cell lines using MTT assay.

Keywords

• Benzo[1,4]oxazines
• 2-oxo-benzo[1,4] oxazines
• 2-oxo-quino[1,4]oxalines
• Antioxidant
• Microwave-Assisted Organic Synthesis (MAOS)
• DPPH
• FRAP