N-QCCA-Novel fragment-based QSAR modeling and combinatorial desig | 5065
Current Synthetic and Systems Biology

Current Synthetic and Systems Biology
Open Access

ISSN: 2332-0737


N-QCCA-Novel fragment-based QSAR modeling and combinatorial design of pyrazole derived CRK3 inhibitors as potent anti-leishmanials

International Conference on Synthetic Biology

September 28-29, 2015 Houston, USA

Abhinav Grover

Jawaharlal Nehru University, India

Posters-Accepted Abstracts: Curr Synthetic Sys Biol

Abstract :

The CRK3 cyclin-dependent kinase of Leishmania plays an important role in regulating the cellcycleprogression at the G2-M phase checkpoint transition, proliferation and viability inside thehost macrophage. In this study, a novel fragment based QSAR model has been developed using22 pyrazole derived compounds exhibiting inhibitory activity against Leishmanial CRK3. Unlikeother 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 biologicalresponse by evaluating cross-term fragment descriptors. Based on the fragment-based QSARmodel, a combinatorial library was generated and top two compounds were reported afterpredicting 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 descriptorsdescribing 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 theinhibitory 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 ofthe designed pyrazole-based leads as potent antileishmanial drugs.

Biography :