{Reference Type}: Journal Article
{Title}: 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.
{Author}: Sharma A;Talimarada D;Dhuri SN;Sundaram VNN;Palanimutu D;Holla H;
{Journal}: Chem Biodivers
{Volume}: 20
{Issue}: 9
{Year}: 2023 Sep 21
{Factor}: 2.745
{DOI}: 10.1002/cbdv.202300371
{Abstract}: The 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.