Cancer is a disease characterized by uncontrolled growth and spread of abnormal cells. The discovery of novel anticancer agents will hopefully provide the desired degree of selectivity for cancer cells, one of the most important therapeutic targets for cancer is Topoisomerase 1, which is enzyme essential for DNA replication, and chromosome segregation. In this present study, computational followed by synthetic approaches were used to design and evaluate small molecules targeting topoisomerase. Twelve molecules were selected to generate pharmacophore model using DISCOtech and refine the generated model from (GASP) Genetic algorithm similarity program. The best model contained 2 donor sites, 2 acceptor atoms and 2 hydrophobic regions and this model was subjected to virtual screening in which about 25,216 molecules were retrieved. Hence we designed the molecule having quinoline moiety from pharmacophore modeling and virtual screening. From docking study we found that our designed molecules showing good score comparative to standard drug. All the newly synthesized compounds were characterized using physical and spectral properties. Anticancer activity was evaluated on three different cell-lines; MCF-7, A-375 and HCT-15 by MTT assay. All compounds showed comparative good activity on all cell line as compared to standard.

Design, synthesis, and in vitro anticancer activities the 7-chloro-6-fluoro-N-subsituted-2-phenylquinoline-4-carboxamide derivatives

249th National Meeting (2015)

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