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