Investigation on quantitatıve structure-activity relationshıps of benzoylamino benzoic acıd derivatives as β-ketoacyl-acyl carrıer protein synthase ııı (fabh) inhibitors

Year 2017, Volume: 21 Issue: 3, 631 - 643, 23.06.2017

Pp Subramani Sv Khare Sp Choudhari S.p Phalle Ss Kumbhar Vs Kavade Aa Pratavale Pb Choudhari

https://doi.org/10.12991/marupj.323295

https://izlik.org/JA29BK24KT

Abstract

Fatty acid biosynthesis is an important process in the

microorganism life cycle. β-Ketoacyl-acyl Carrier Protein

Synthase III (FABH) catalyzes a critical step in fatty acid

biosynthesis via type ii fatty acid biosynthesis. Series of 43

Benzoyl amino benzoic acid derivatives were subjected to 2D

and 3D quantitative structure-activity relationships (QSAR)

analysis via multiple linear regression and partial least square

analysis respectively. Statistically significant four QSAR 

models were developed with good cross-validated correlation

coefficient and external validation values. Developed QSAR

model indicated the significance of the lipophilic parameters

in an inhibitory potential of benzoyl amino benzoic acid

derivatives.

Keywords

QSAR , Benzoyl amino benzoic acid , FabHβ- Ketoacyl-acyl Carrier Protein Synthase III , Partial least square (PLS) , Multiple linear regression (MLR)

References

• 1. Mohajan HK. Tuberculosis is a fatal disease among some developing countries of the world. Am J Infect Dis 2015; 3: 18-31. 2. Choi KH, Heath RJ, Rock CO. Beta-ketoacyl-acyl carrier protein synthase III (FabH) is a determining factor in branched-chain fatty acid biosynthesis. J Bacteriol 2000; 182: 365-70 3. Choi KH, Kremer L, Besra GS, Rock CO. Identification and substrate specificity of beta -ketoacyl (acyl carrier protein) synthase III (mtFabH) from Mycobacterium tuberculosis. J Biol Chem. 2000; 275: 28201-7. 4. Han L, Lobo S, Reynolds KA. Characterization of betaketoacyl- acyl carrier protein synthase III from Streptomyces glaucescens and its role in initiation of fatty acid biosynthesis. J Bacteriol 1998; 180:4481-6. 5. Veyron-Churlet R, Guerrini O, Mourey L, Daffé M, Zerbib D. Protein-protein interactions within the Fatty Acid Synthase-II system of Mycobacterium tuberculosis are essential for mycobacterial viability. Mol Microbiol 2004; 54:1161-72. 6. Chatterjee D. The mycobacterial cell wall: structure, biosynthesis and sites of drug action Curr Opin Chem Biol 1997; 1:579-88 7. Cohen-Gonsaud M1, Ducasse S, Hoh F, Zerbib D, Labesse G, Quemard A. Crystal structure of MabA from Mycobacterium tuberculosis, a reductase involved in long-chain fatty acid biosynthesis. J Mol Biol 2002; 320:249-61. 8. Heath RJ, White SW, Rock CO. Lipid biosynthesis as a target for antibacterial agents. Prog Lipid Res 2001 ;40:467-97. 9. Rock CO, Jackowski S. Forty years of bacterial fatty acid synthesis. Biochem Biophys Res Commun 2002; 292:1155-66. 10. Heath RJ, White SW, Rock CO. Inhibitors of fatty acid synthesis as antimicrobial chemotherapeutics. Appl Microbiol Biotechnol 2002; 58:695-703. 11. Tsay JT, Oh W, Larson TJ, Jackowski S, Rock CO. Isolation and characterization of the beta-ketoacyl-acyl carrier protein synthase III gene (fabH) from Escherichia coli K-12. J Biol Chem 1992; 267:6807-14. 12. Choudhari PB, Bhatia MS. 3D QSAR, docking studies, and pharmacophore modeling of selected factor Xa inhibitors. Med Chem Res 2012; 21: 1427-32. 13. Choudhari PB, Bhatia MS, Bhatia NM. Application of pocket modeling and k-nearest neighbor molecular field analysis (kNN-MFA) for designing of some anticoagulants: potential factor IXa inhibitors. Med Chem Res 2013; 22: 976-5. 14. Nie Z, Perretta C, Lu J, Su Y, Margosiak S, Gajiwala KS, Cortez J, Nikulin V, Yager KM, Appelt K, Chu S. Structurebased design, synthesis, and study of potent inhibitors of beta-ketoacyl-acyl carrier protein synthase III as potential antimicrobial agents. J Med Chem 2005; 48:1596-609. 15. Ashek A, Cho SJ. A combined approach of docking and 3D QSAR study of beta-ketoacyl-acyl carrier protein synthase III (FabH) inhibitors. Bioorg Med Chem 2006;14:1474-82. 16. Ashek A, San Juan AA, Cho SJ. HQSAR study of beta-ketoacylacyl carrier protein synthase III (FabH) inhibitors. J Enzyme Inhib Med Chem 2007; 22:7-14.