A Molecular Docking Study of Aristolactam Analogues against Polo-Box Domain (PBD) of Human Polo Like kinase-1 in Cancer Progression

Polo like kinases (Plks) play a multiful role in the cell cycle progression and its mis -regulation in cancer believed as a promising anticancer-drug target. The N-terminal polo box domain(PBD) of plk1is another efficient target for potent plk1 inhibition. Natural Aristolactam analogues have show n anticancer activity,but their cellular target was unknown. In this work, molecular docking studies were performed in order to see the interaction of Aristolactam and its 11analogues with human plk1 in cancer. Results shown that among 11, three analogues exhibited good affinity to the PBD of plk1 with free energy of -8.10,-7.47 and -7.10 Kcal/mol and inhibition constant(Ki) of 1.16,3.33 and 6.61 µM. Active site residues of PBD interacting with Aristolactam analogues were Trp Abstract Polo like kinases (Plks) play a multiful role in the cell cycle progression and its mis -regulation in cancer believed as a promising anticancer-drug target. The N-terminal polo box domain(PBD) of plk1is another efficient target for potent plk1 inhibition. Natural Aristolactam analogues have show n anticancer activity,but their cellular target was unknown. In this work, molecular docking studies were performed in order to see the interaction of Aristolactam and its 11analogues with human plk1 in cancer. Results shown that among 11, three analogues exhibited good affinity to the PBD of plk1 with free energy of -8.10,-7.47 and -7.10 Kcal/mol and inhibition constant(Ki) of 1.16,3.33 and 6.61 µM. Active site residues of PBD interacting with Aristolactam analogues were Trp 414 ,Lys 540 ,Leu 491 ,Asn 533 ,Ser 412 ,Arg 516 ,Arg 594 ,Asp 371 andTyr 510 . The inhibitor for the plk1,BI2523 was used as reference drug and it was shown poor docking energy compared to Aristolactam analogues. In binding mode, the length (A) of H-bonds were varied from each analogue. These interactions indicated that stability of Aristolactams in PBD of plk1 and suggested as a potential drug candidates. Thus good affinity of Aristolactam analogues to plk1 may leads to synthesis of anticancer drugs. Abstract Polo like kinases (Plks) play a multiful role in the cell cycle progression and its mis -regulation in cancer believed as a promising anticancer-drug target. The N-terminal polo box domain(PBD) of plk1is another efficient target for potent plk1 inhibition. Natural Aristolactam analogues have show n anticancer activity,but their cellular target was unknown. In this work, molecular docking studies were performed in order to see the interaction of Aristolactam and its 11analogues with human plk1 in cancer. Results shown that among 11, three analogues exhibited good affinity to the PBD of plk1 with free energy of -8.10,-7.47 and -7.10 Kcal/mol and inhibition constant(Ki) of 1.16,3.33 and 6.61 µM. Active site residues of PBD interacting with Aristolactam analogues were Trp 414 ,Lys 540 ,Leu 491 ,Asn 533 ,Ser 412 ,Arg 516 ,Arg 594 ,Asp 371 andTyr 510 . The inhibitor for the plk1,BI2523 was used as reference drug and it was shown poor docking energy compared to Aristolactam analogues. In binding mode, the length (A) of H-bonds were varied from each analogue. These interactions indicated that stability of Aristolactams in PBD of plk1 and suggested as a potential drug candidates. Thus good affinity of Aristolactam analogues to plk1 may leads to synthesis of anticancer drugs.