Development of pyridine dicoumarols as potent anti HIV-1 leads, targeting HIV-1 associated topoisomeraseII beta kinase

摘要

Aim: A structural study of a series of pyridine dicoumarol derivatives with potential activity against a novel Topoisomerase II beta kinase which was identified in the HIV-1 viral lysate, compounds were designed and synthesized based on a 3D-QSAR study. Materials & methods: Based on QSAR model we have designed and synthesized a series of pyridine dicoumarol derivatives and characterized by spectral studies, all the molecules are biologically evaluated by kinase assay, cytotoxicity assay, ELISA and PCR method. Result: We demonstrated the achievement of water soluble disodium pyridine dicoumarate derivatives showing high anti-HIV-1 activity (IC50 < 25 nM) which provides a crucial point for further development of pyridine dicoumarol series as HIV1-associated topoisomerase II beta kinase inhibitors for clinical application against AIDS. Conclusion: A new class of anti-HIV-1 lead compounds have been designed and tested. Further studies would result in development of novel and potential drugs.