An enzoinformatics study targeting polo-like kinases-1 enzyme: Comparative assessment of anticancer potential of compounds isolated from leaves of Ageratum houstonianum

Natural products from plant sources, embracing inherently ample structural diversity than synthetic ones are the major sources of anticancer agents and will constantly play as protagonists for discovering new drugs. Polo-like kinases (PLKs) play a leading role in the ordered execution of mitotic events and 4 mammalian PLK family members have been identified. PLK1 is an attractive target for anticancer drugs in mammalian cells, among the four members of PLKs. The present study expresses the molecular interaction of compounds (1,2-Benzenedicarboxylic acid bis (2 ethylhexyl) ester, squalene, 3,5-bis (1,1-dimethylethyl) phenol, Pentamethyl tetrahydro-5H-chromene, (1,4-Cyclohexylphenyl) ethanone and 6-Vinyl-7-methoxy-2,2-dimethylchromene) isolated from methanolic extract of leaves of Ageratum houstonianum with PLK1 enzyme. Docking between PLK1 and each of these compounds (separately) was performed using “Auto dock 4.2.” (1,4-Cyclohexylphenyl) ethanone showed the maximum potential as a promising inhibitor of PLK1 enzyme with reference to ∆G (−6.84 kcal/mol) and Ki (9.77 μM) values. This was sequentially followed by Pentamethyl tetrahydro-5H-chromene (∆G = −6.60 kcal/mol; Ki = 14.58 μM), squalene (∆G = −6.17 kcal/mol; Ki = 30.12 μM), 6-Vinyl-7-methoxy-2,2-dimethylchromene (∆G = −5.91 kcal/mol; Ki = 46.68 μM), 3, 5-bis (1,1-dimethylethyl) phenol (∆G = −5.70 kcal/mol; Ki = 66.68 μM) and 1,2-Benzenedicarboxylic acid bis (2 ethylhexyl) ester (∆G = −5.58 kcal/mol; Ki = 80.80 μM). These results suggest that (1,4-Cyclohexylphenyl) ethanone might be a potent PLK1 inhibitor. Further, in vitro and in vivo rumination are warranted to validate the anticancer potential of (1,4-Cyclohexylphenyl) ethanone.