Synthesis of cyclic 1,9-acetal derivatives of forskolin and their bioactivity evaluation.

Abstract

A new series of 1,9-acetals of forskolin were synthesized by treating with aromatic and aliphatic aldehydes using Ceric ammonium nitrate as catalyst and evaluated for anticancer and α-glucosidase inhibition activities. Among the synthesized compounds 2a, 2b and 3a showed potential cytotoxic activity towards human cancer cell lines MCF-7 (Human Breast Adenocarcinoma), MDA-MB (Human Breast Carcinoma), HeLa (Human Cervix Adenocarcinoma), A498 (Human Kidney Carcinoma), K562 (Human Erythromyeloblastoid leukemia), SH-SY5Y (Human Neuroblastoma), Hek293 (Human Embryonic Kidney) and WRL68 (Human Hepatic) with IC50 values ranging between 0.95 and 47.96 μg/ml. Osmotic fragility test revealed compound 3a as non-toxic to human erythrocytes at the tested concentrations of 50 and 100 μg/ml. Compounds 1g (IC50 value 0.76 μg/ml) and 1p (IC50 value 0.74 μg/ml) significantly inhibited α-glucosidase in in vitro system. In silico based docking, ADME and toxicity risk assessment studies also showed discernible α-glucosidase activity for compounds 1g, 1p compared to standard acarbose.