Synthesis and characterization of steroidal heterocyclic compounds, DNA condensation and molecular docking studies and their in vitro anticancer and acetylcholinesterase inhibition activities

Abstract

A facile, convenient and efficient approach for the synthesis of a new series of steroidal heterocyclic compounds (4–12) by reacting a mixture of compounds (1e–3e) with o-aminothiophenol/o-aminophenol/o-phenylenediamine is reported. The structural assignment of products is confirmed on the basis of IR, ¹H NMR, ¹³C NMR, MS and analytical data. The compounds obey the Lipinski's ‘Rule of Five’ analysis based on computational prediction and pharmacokinetic properties. The anticancer activity has been tested in vitro against three cancer cell lines Hep3B (human hepatocellular carcinoma), MCF7 (human breast adenocarcinoma), HeLa (human cervical carcinoma) and one non-cancer normal cell i.e. PBMCs (peripheral blood mononuclear cell) by MTT assay. In addition, the synthesized compounds are also tested for their in vitro antioxidant activity by various reported methods in which compounds 10–12 exhibited good antioxidant activity. Nonenzymatic degradation of DNA has been investigated. The acetylcholinesterase (AChE) inhibitor activities of the steroidal derivatives are also evaluated using Ellman's method. Moreover, the application of compound 6 as a DNA gene transporter is evaluated by DNA condensation and ascertained by employing TEM and AFM, which illustrate that the compound 6 induces the condensation of CT-DNA. Molecular docking studies further characterize the interaction of the synthesized compounds with DNA.