Discovery of Camptothecin based Topoisomerase I Inhibitors: Identification Using an Atom based 3D-QSAR, Pharmacophore Modeling, Virtual Screening and Molecular Docking Approach.

Discovery of Camptothecin based Topoisomerase I Inhibitors: Identification Using an Atom based 3D-QSAR, Pharmacophore Modeling, Virtual Screening and Molecular Docking Approach. Comb Chem High Throughput Screen. 2016 Aug 10; Authors: Dev S, Dhaneshwar SR, Mathew B Abstract Camptothecin is a quinolone containing alkaloid isolated from the Chinese tree Camptotheca acuminate and exhibited its cytotoxicity activity by the inhibition of nuclear enzyme topoisomerase I (topo I). Camptothecin and its analogs binds with topo I and DNA complex form, which can arrest the tumor growth by interfering the various transactions mechanism of DNA. Besides its strong anticancer potential, the low solubility as well as instability of the hydroxylactone ring (Ring E) limits the clinical application Camptothecin. In the present work, the scaffold perception technique is employed to explore novel scaffolds with potential topo I inhibitor activity by performing an atom based 3D-QSAR and pharmacophore modeling using a series of Camptothecin analogues. The top ranked pharmacophore model was subsequently used as a query to screen compounds from 'zinc drug like database'. Docking study of the hits identified from virtual screening revealed the binding affinity of these inhibitors at the active site of Topoisomerase enzyme. Post docking calculation using MM/GBSA and in silico ADME predictions was also performed. These findings provide a new insight for designing...
Source: Combinatorial Chemistry and High Throughput Screening - Category: Chemistry Authors: Tags: Comb Chem High Throughput Screen Source Type: research