Synthesis and 3D-QSAR study of 1,4-dihydropyridine derivatives as MDR cancer reverters

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. [Display omitted] This paper reports synthesis of 1,4-dihydropyridine derivatives and their tumor cell cytotoxicity followed by field based and similarity based 3D-QSAR to decipher the factors governing MDR reversing ability in cancer. •1,4-DHPs were synthesized by microwave irradiation and conventional approach.•Molecules were screened against mdr1 gene expressing tumor cell lines HL-60.•Highly predictive 3D-QSAR models were derived using CoMFA and CoMSIA techniques.•New potent molecules were designed using 3D contour maps derived in 3D-QSAR.