ABSTRACT
A series of symmetrical and unsymmetrical 1,4-dihydropyridines were synthesized by a rapid, single pot microwave irradiation (MWI) based protocol along with conventional approach and characterized by NMR, IR and mass spectroscopic techniques. The compounds were evaluated for their tumor cell cytotoxicity in HL-60 tumor cells. A 3D-QSAR study using CoMFA and CoMSIA was carried out to decipher the factors governing MDR reversing ability in cancer. The resulting contour maps derived by the best 3D-QSAR models provide a good insight into the molecular features relevant to the biological activity in this series of analogs. 3D contour maps as a result of 3D-QSAR were utilized to identify some novel features that can be incorporated into the 1,4-dihydropyridine framework to enhance the activity.
Subject(s)
Dihydropyridines/chemical synthesis , Dihydropyridines/pharmacology , Drug Resistance, Multiple/drug effects , Drug Resistance, Neoplasm/drug effects , Quantitative Structure-Activity RelationshipABSTRACT
AIM: To explore mitochondrial mechanisms of apoptosis induced by artesunate in human leukemia HL60 cells. METHODS: Human leukemia HL60 cell lines were treated by artesunate. The inhibitory effect on cell proliferation was assessed by MTT assay. Electron microscopy and DNA gel electrophoresis was applied to demonstrate the presence of apoptosis. The level of MMP, cell cycle were determined by flow cytometry (FCM). The activity of caspase 3 was observed by colorimetry. RESULTS: Art showed a dose dependent and time dependent manner on the growth of HL60 cells (P
