Discovery of Novel Lead Compounds Against Different DHFR through Pharmacophore Design, Database Mining  (English, Paperback, Dr. Ruchi Mishra)

Dihydrofolate reductase (DHFR) catalyzes the reduction of folate or 7,8−dihydrofolate to tetrahydrofolate and intimately couples with thymidylate synthase (TS). This is the exclusive de novo sources of dTMP, hence inhibition of DHFR or TS activity leads to “thymineless death.” Thus, DHFR inhibition has long been an attractive goal for the development of chemotherapeutic agents against bacterial and parasitic infections as well as cancer. Pharmacophore based drug design has been now considered as a powerful approach and has found wide applications in drug design because of the pressing need to reduce the time & cost of candidate drug molecule in discovery phase where the current emphasis is on more rational approaches than trial and error to identify new chemical entities (NCE). In view of this and the urgency to identify new dihyrofolate reductase (DHFR) inhibitors, the main objectives of proposed research endeavor are -  To perform ligand-based drug design (LBDD) and structure based drug design (SBDD).  To use developed pharmacophore for the identification of novel dihydrofolate reductase (DHFR) inhibitors as high affinity ligands against Cancer, Malaria, Pneumocystis crainii Pneumonia (PCP) and Diarrhea.  To create virtual counter screen filters to find high-affinity inhibitor of various DHFRs from drug databases.  To predict the affinity of ligands for the various DHFRs.  To validate the finding of In-silico approach through In-vitro evaluation