‘Cephalandole A’ analogues as a new class of antioxidant agents: Design, microwave-assisted synthesis, bioevaluation, SAR and in silico studies

Abstract

Herein, a novel series of natural product alkaloid ‘Cephalandole A’ analogues 19a-y, and 20a-d were rapidly synthesised under microwave irradiation conditions using PTSA in catalytic amount dissolved in acetonitrile at 90 °C for 15 min. The developed one-pot protocol is operationally simple, rapid (15 min) and furnished the target analogues in up to 90 % yield. All the synthesised analogues of Cephalandole A were evaluated for their in vitro antioxidant activity using DPPH free-radical scavenging and FRAP assays. The in vitro studies of DPPH radical scavenging assay provided 19a (IC50 = 11.87 ± 0.14 µg/mL), 19f (IC50 = 16.34 ± 0.27 µg/mL), 19n (IC50 = 15.37 ± 0.11 µg/mL) and 20a (IC50 = 14.54 ± 0.31 µg/mL) respectively, as the most active compounds of the series. In addition, the analogous 19d (556.3 ± 13.1 µM) and 19v (551.9 ± 14.2 µM) showed promising activity in FRAP assay. However, the standard reference drug ascorbic acid showed an IC50 value of 4.57 µg/mL in the DPPH assay, and BHT showed C0.5FRAP = 546.0 ± 13.6 μM in the FRAP assay. In silico studies were performed to validate the wet results. To the best of our knowledge, this is the first report demonstrating ‘Cephalandole A’ analogues as a new class of antioxidant agents.