Isolation, Structure Elucidation and in Vitro Anticancer Activity of Phytochemical Constituents of Goniothalamus wynaadensis Bedd. and Identification of α‐Tubulin as a Putative Molecular Target by in Silico Study

Abstract

AbstractThe phytochemical analysis of ethyl acetate and methanol extract of Goniothalamus wynaadensis Bedd. leaves led to an isolation of eight (1–8) known molecules, among them seven (2–8) isolated for the first time from this species, which includes (+)‐goniothalamin oxide (2), goniodiol‐7‐monoacetate (3), goniodiol‐8‐monoacetate (4), goniodiol (5), (+)‐8‐epi‐9‐deoxygoniopypyrone (6) etc. The phytochemical modification by acetylation of 3 and 4 gave goniodiol diacetate (9) with absolute configuration (6R, 7R, 8R) confirmed by single crystal X‐ray diffraction. Compounds 3–9 were cytotoxic against breast, ovarian, prostate and colon cancer cell lines with IC50<10 μM. Cell cycle analysis and Annexin‐V assay on MDA‐MB‐231 cell using goniodiol‐7‐monoacetate (3) exhibited apoptotic response as well as necrotic response and showed cell proliferation arrest at G2/M phase. An in silico target identification for these molecules was carried out with an α‐tubulin protein target by covalent docking. To gain an in‐depth understanding and identify the stability of these protein‐ligand complexes on thermodynamic energy levels, further assessment of the isolated molecules binding to the Cys‐316 of α‐tubulin was performed based on reaction energetic analysis via DFT studies which hinted the isolated molecules may be α‐tubulin inhibitors similar to Pironetin. Molecular dynamics reiterated the observations.