Investigation of QSAR kNN-MFA on a Series of Substituted Chromen-2-one Derivatives as FXa Inhibitors

Santosh S Kumbhar, Manish S Bhatia, Prafulla B Choudhari

Abstract


Factor Xa (FXa), a trypsin-like serine protease, forms a well-known target for development of anticoagulants. Various molecules have been reported as Factor Xa inhibitors but most of them have pharmacokinetic issues. Quantitative understanding of the structure activity relationship of already developed inhibitors can overcome pharmacokinetic issues. With this aim, we performed development and validation of the (3D-QSAR) k-nearest neighbour molecular field analysis (kNN-MFA). The QSAR models of chromen-2-one derivatives were developed by kNN-MFA to identify an effective inhibitor of FXa. The results of QSAR study showed that more steric and electronegative groups are the important features for anticoagulant activity. The selected 3D kNN-MFA model B has training set of 44 molecules and test set of 20 molecules having validation (q2) and cross validation (pred_r2) values 0.7110 and 0.5947 respectively. The results of 3D QSAR models may lead to better understanding of design and development of novel FXa inhibitors.

Keywords


3D-QSAR; kNN-MFA model; FXa; Vlife MDS; Anticoagulant

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