QSAR studies on benzoylaminobenzoic acid derivatives as inhibitors of beta-ketoacyl-acyl carrier protein synthase III.
Fatty acid biosynthesis is essential for most of the bacterial survival. Components of this biosynthetic pathway have been identified as attractive targets for the development of new antibacterial agents. FabH, beta-ketoacyl-ACP synthase III, is a attractive target since it is central to the initiation of fatty acid biosynthesis. Quantitative structure-activity relationship (QSAR) studies have been carried out on a series of benzoylaminobenzoic acid derivatives as potent inhibitors of FabH and antibacterial activity against Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Enterococcus faecalis, Neisseria meningitidis and Escherichia coli, which demonstrate FabH inhibitory activity in cell free and whole cell system. The QSAR studies revealed that inhibitory activity increases with increase in hydrophobicity, molar refractivity, aromaticity, and presence of OH group (on x position of the nucleus). On the other side presence of hetero-atoms like N, O, or S at R(1) position of the nucleus decreases the inhibitory activity. The comparison of QSAR between the FabH inhibitory activity and antibacterial activity against S. aureus, S. pneumoniae, S. pyogenes, E. faecalis, N. meningitidis also demonstrates that the hydrophobicity, aromaticity and presence of OH group (on x position of the nucleus) are conducive for the inhibitory activity.
Singh
Satyakam
S
Molecular Modelling Study Group, CADD Laboratory, Department of Pharmacy, Shri G.S. Institute of Technology and Science, 23 Park Road, Indore 452 003, Madhya Pradesh, India.
Soni
Love K
LK
Gupta
Manish K
MK
Prabhakar
Yenamandra S
YS
Kaskhedikar
S G
SG
D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / Q000037:antagonists & inhibitors*; D010129:4-Aminobenzoic Acid / Q000138:chemical synthesis* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D016014:Linear Models; D008826:Microbial Sensitivity Tests; D021281:Quantitative Structure-Activity Relationship; D062366:para-Aminobenzoates
D000900:Anti-Bacterial Agents; D062366:para-Aminobenzoates; C077402:3-ketoacyl-acyl carrier protein synthase III; D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase; D010129:4-Aminobenzoic Acid