Antidiabetic, antioxidant and cytotoxicity activities of ortho- and para-substituted Schiff bases derived from metformin hydrochloride: Validation by molecular docking and in silico ADME studies

Abstract

Abstract This work evaluates the in vitro antioxidant and antidiabetic activities of two metformin hydrochloride-based Schiff bases. Moreover, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to examine the in vitro cytotoxic effects of HL1 and HL2 on the A549 lung cancer cell line. The two Schiff bases that have been previously synthesized by using two effective, green techniques, namely stirring and microwave-assisted, are N,N-dimethyl-N′-[(Z)-(2-nitrophenyl) methylidene] imidodicarbonimidic diamide and N,N-dimethyl-N′-[(Z)-(4-nitrophenyl) methylidene] imidodicarbonimidic diamide, indicated by HL1 and HL2, respectively. Studies of antidiabetic efficacy using alpha-amylase revealed that HL2 has a higher inhibition than HL1, but the results on sucrase enzyme showed that HL1 had the highest inhibitory action, whereas the outcome of the antioxidant test with the 2,2-diphenyl-1-picrylhydrazyl assay demonstrated that HL2 was the most effective antioxidant, followed by ascorbic acid and HL1. In the MTT assay, HL1 had the best result, with an IC50 value of 57.13 µg/mL compared to HL2 with an IC50 value of 76.83 µg/mL. It was observed that HL1 was the most effective against the human lung cancer cell line A459. The findings were supported by computational and pharmacokinetic studies (SwissADME). Based on empirical and computational studies, we suggest that HL1 and HL2 are promising candidates as antioxidants and antidiabetics after being examined in vivo.