Computer-aided anticancer drug design: In vitro and in silico studies of new iminocoumarin derivative

Abstract

In this study, the aim was computer-aided design of a new anti-cancer drug molecule. For this purpose, 7-hydroxy-8-(((1-hydroxy-3-phenylpropan-2-yl)imino)methyl)-4-(trifluoromethyl)-2H-chromen-2-one (D3) was synthesized by the condensation reaction. Its characterization studies were performed by NMR, FTIR, MS and UV spectral data. Anti-cancer activity of D3 was examined on MCF-7, HeLa and Mat-Lylu cell lines, and it was found that D3 showed cytotoxic activity in all cell lines. Mutagenity of D3 was determined by Ames/Salmonella assay, and it was found that it had no mutagenic effect on S. ty-phimurium TA98 and TA100 strains. Antioxidant activity of D3 was also revealed. Besides, the interaction of D3 with DNA was investigated by the UV titration method. Experimental results showed D3 binds to DNA by intercalation or groove linking. Moreover, molecular docking approach was used to elucidate the atomic level interaction between the synthesized compound and DNA; thus, the atomic level behavior of the compound in the binding site of DNA was characterized and its binding properties were determined. In addition, the physicochemical and pharmacokinetic properties of the synthesized compound were per -formed using ADMET and frontier orbital analyses. In conclusion, according to both in vitro and in silico findings, it can be suggested that D3 may be used as a new anti-cancer drug for breast, cervical and prostate cancers. (c) 2021 Elsevier B.V. All rights reserved.