Jawaharlal Nehru University, India
Abhinav Grover has completed his PhD at the age of 26 years from Indian Institute of Technology Delhi (IITD) and Postdoctoral studies from IITD and Jawaharlal Nehru University (JNU). He is currently working as Assistant Professor in School of Biotechnology, JNU. He has published more than 40 papers in reputed journals and has been serving as Reviewer of a plethora of reputed journals. He has been awarded with various national and international honors, distinctions and awards.
The CRK3 cyclin-dependent kinase of Leishmania plays an important role in regulating the cell cycle progression at the G2-M phase checkpoint transition, proliferation and viability inside the host macrophage. In this study, a novel fragment based QSAR model has been developed using 22 pyrazole derived compounds exhibiting inhibitory activity against Leishmanial CRK3. Unlike other QSAR methods, this fragment based method gives flexibility to study the relationship between molecular fragments of interest and their contribution for the variation in the biological response by evaluating cross-term fragment descriptors. Based on the fragment-based QSAR model, a combinatorial library was generated and top two compounds were reported after predicting their activity. The QSAR model showed satisfactory statistical parameters for the dataset (r2=0.8752, q2=0.6690, F-ratio=30.37 and pred-r2=0.8632) with four descriptors describing the nature of substituent groups and the environment of the substitution site. Evaluation of the model implied that electron-rich substitution at R1 position improves the inhibitory activity while decline in inhibitory activity was observed in presence of nitrogen at R2 position. The analysis carried out in this study provides a substantial basis for consideration of the designed pyrazole-based leads as potent anti-leishmanial drugs.