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Synthesis and molecular modeling of six novel monastrol analogues: evaluation of cytotoxicity and kinesin inhibitory activity against HeLa cell line.

ABSTRACT: A common approach in cancer chemotherapy is development of drugs that interrupt the mitosis phase of cell division. Dimethylenastron is a known kinesin inhibitor. In this study, six novel dimethylenastron analogues (4a-f), in which 3-hydroxyphenyl substituent has been replaced with substituted benzylimidazolyl, were synthesized through Biginelli reaction.Six novel Biginelli compounds (4a-f) were synthesized through one step Biginelli reaction of imidazole aldehydes (3a-c), dimedone and urea or thioura. In vitro cytotoxicities of prepared compounds were investigated using MTT assay. Furthermore the ELIPA kit was implemented to study inhibitory effects of synthesized compounds on ATPase activity of kinesin by measuring of organic phosphate.Our results indicated that analogue 4c is the most toxic and analogues 4f, 4b and dimethylenasteron were less cytotoxic in compare with other analogues. On the other hand, analogue 4a, 4b, 4c and 4e showed stronger Kinesin inhibition as compared with analogue 4f and dimethylenasteron. None of synthesized compounds were as potent kinesin inhibitor as Taxol. Docking analysis revealed that hydrogen bond formation and hydrophobic interactions were the key factors affecting inhibitory effects of these compounds.Newly synthesized compounds were found to have moderate to good cytotoxicity against HeLa cancer cell. Our results may be helpful in further design of dihydropyrimidine as potential anticancer agents.

SUBMITTER: Abnous K

PROVIDER: S-EPMC3891991 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Monastrol mimic Biginelli dihydropyrimidinone derivatives: synthesis, cytotoxicity screening against HepG2 and HeLa cell lines and molecular modeling study.

Project description:Biginelli dihydropyrimidinone derivatives as structural analogs of monastrol, a known human kinesin Eg5 inhibitor, were synthesized. IC50 values of the synthesized compounds against the proliferation of human hepatocellular carcinoma and human epithelial carcinoma cell lines were determined through MTT assay. Molecular docking study gave a clear insight into the structural activity relationship of the compounds in comparison with monastrol.

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| S-EPMC1462975 | biostudies-literature

Monastrol derivatives: in silico and in vitro cytotoxicity assessments.

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Effect of N-1 arylation of monastrol on kinesin Eg5 inhibition in glioma cell lines.

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| S-EPMC6072436 | biostudies-literature

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| S-EPMC3502167 | biostudies-literature

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