Exploring Structural Requirements for a Class of Nucleoside Inhibitors (PfdUTPase) as Antimalarials: First Report on QSAR, Pharmacophore Mapping and Multiple Docking Studies.

Exploring Structural Requirements for a Class of Nucleoside Inhibitors (PfdUTPase) as Antimalarials: First Report on QSAR, Pharmacophore Mapping and Multiple Docking Studies. Comb Chem High Throughput Screen. 2013 May 20; Authors: Ojha PK, Roy K Abstract Multi-drug resistance to the available antimalarial drugs is a major threat for malaria treatment. Due to the recent characterization of human and parasite genome sequences, both ligand and target based drug design strategies may be helpful for the design of potential antimalarial compounds with reduced degree of resistance. The present work deals with quantitative structure-activity relationship (QSAR) modeling, pharmacophore mapping and docking studies of a series of 95 nucleoside analogs as inhibitors of Plasmodium falciparum deoxyuridine-5'-triphosphate nucleotidohydrolase (PfdUTPase), an enzyme involved in nucleotide metabolism that acts as a first line of defence against uracil incorporation into DNA. The QSAR and pharmacophore models were validated both internally and externally showing good statistical results. The docking study was performed and validated using three different software tools namely Discovery Studio 2.1 (Accelrys), Maestro 9.3 (Schrodinger) and MOE (Chemical Computing Group). The QSAR studies revealed that compounds containing substituted aromatic carbons (aasC fragment) and those bearing hydroxyl groups without an n-oxolane ring exert potent PfdUTPase inhibitory activ...
Source: Combinatorial Chemistry and High Throughput Screening - Category: Chemistry Authors: Tags: Comb Chem High Throughput Screen Source Type: research