CC  Vol.3 No.4 , October 2015
2D-QSAR Study of a Series of Pyrazoline-Based Anti-Tubercular Agents Using Genetic Function Approximation
Abstract: A series of pyrazoline-based new heterocycles have recently been synthesized from our group where some of the compounds display potent anti-tubercular activity against Mycobacterium tuberculosis H37Rv. In order to further explore the potency of the compounds, quantitative structure activity relationship study is carried out using genetic function approximation. Statistically significant (r2 = 0.85) and predictive (r2pred=0.89 and r2m=0.74) QSAR models are developed. It is evident from the QSAR study that majority of the anti-tubercular activity is found to be driven by lipophilicity. Also, molecular solubility, Jurs and shadow descriptors influence the biological activity significantly. Also, positive contribution of molecular shadow descriptors suggests that molecules with bulkier substituents are more likely to enhance anti-tubercular activity. Since the developed QSAR models are found to be statistically significant and predictive, they potentially can be applied for predicting anti-tubercular activity of new molecules for prioritization of molecules for synthesis.
Cite this paper: Soni, H. , Patel, P. , Chhabria, M. , Rana, D. , Mahajan, B. and Brahmkshatriya, P. (2015) 2D-QSAR Study of a Series of Pyrazoline-Based Anti-Tubercular Agents Using Genetic Function Approximation. Computational Chemistry, 3, 45-53. doi: 10.4236/cc.2015.34006.

[1]   Dye, C., Lonnroth, K., Jaramillo, E., Williams, B.G. and Raviglione, M. (2009) Trends in Tuberculosis Incidence and Their Determinants in 134 Countries. Bull, 87, 683-691.

[2]   Cole, S.T. and Riccardi, G. (2011) New Tuberculosis Drugs on the Horizon. Current Opinion in Microbiology, 14, 570-576.

[3]   Udwadia, Z. F., Amale, R.A., Ajbani, K.K. and Rodrigues, C. (2012) Totally Drug-Resistant Tuberculosis in India. Clinical Infectious Diseases, 54, 579-581.

[4]   Chhabria, M.T., Mahajan, B.M. and Brahmkshatriya, P.S. (2011) QSAR Study of a Series of Acyl Coenzyme A (CoA): Cholesterol Acyltransferase Inhibitors Using Genetic Function Approximation. Medicinal Chemistry Research, 20, 1573-1580.

[5]   Buha, V.M., Rana, D.N., Chhabria, M.T., Chikhalia, K.H., Mahajan, B.M., Brahmkshatriya, P.S. and Shah, N.K. (2013) Synthesis, Biological Evaluation and QSAR Study of a Series of Substituted Quinazolines as Antimicrobial Agents. Medicinal Chemistry Research, 22, 4096-4109.

[6]   Tropsha, A. (2010) Best Practices for QSAR Model Development, Validation, and Exploitation. Molecular Informatics, 29, 476-488.

[7]   Ertan, T., Yildiz, I., Tekiner-Gulbas, B., Bolelli, K., Temiz-Arpaci, O., Ozkan, S., Yalcin, I. and Aki, E. (2009) Synthesis, Biological Evaluation and 2D-QSAR Analysis of Benzoxazoles as Antimicrobial Agents. European Journal of Medicinal Chemistry, 44, 501-510.

[8]   Rana, D.N., Chhabria, M.T., Shah, N.K. and Brahmkshatriya, P.S. (2014) Pharmacophore Combination as a Useful Strategy to Discover New Antitubercular Agents. Medicinal Chemistry Research, 23, 370-381.

[9]   Rana, D.N., Chhabria, M.T., Shah, N.K. and Brahmkshatriya, P.S. (2014) Discovery of New Antitubercular Agents by Combining Pyrazoline and Benzoxazole Pharmacophores: Design, Synthesis and Insights into the Binding Interactions. Medicinal Chemistry Research, 23, 2218-2228.

[10]   Rogers, D. and Hopfinger, A.J. (1994) Application of Genetic Function Approximation to Quantitative Structure-Activity Relationships and Quantitative Structure-Property Relationships. Journal of Chemical Information and Computer Sciences, 34, 854-866.

[11]   Jaiswal, M., Khadikar, P.V., Scozzafava, A. and Supuran, C.T. (2004) Carbonic Anhydrase Inhibitors: The First QSAR Study on Inhibition of Tumor-Associated Isoenzyme IX with Aromatic and Heterocyclic Sulfonamides. Bioorganic & Medicinal Chemistry Letters, 14, 3283-3290.

[12]   Roy, P.P. and Roy, K. (2007) On Some Aspects of Variable Selection for Partial Least Squares Regression Models. QSAR & Combinatorial Science, 27, 302-313.

[13]   Stanton, D.T. and Jurs, P.C. (1990) Development and Use of Charged Partial Surface Area Structural Descriptors in Computer Assissted Quantitative Structure Property Relationship Studies. Analytical Chemistry, 62, 2323-2329.