QSAR Study Of The Antimicrobial Activity Of Fatty Acids And Their Derivatives

Fatty acids and their derivatives are important resources of natural and potentantimicrobial. Although there are lots of relative studies, it's still prospective toscreening more potent antimicrobial agents among fatty acids and their derivatives. Thepresent screening work was depending on previous researches and abundantexperiments, being kind of a lottery. It is necessary to understand the relationshipbetween the structure and the antimicrobial activities of fatty acids and fatty acidderivatives. In this study, MICs of 57 fatty acids and fatty acid derivatives againstStaphylococcus aureus and Escherichia coli were examined, SDQSAR (StructureDescriptors regression Quantitative Structure-Activity Relationship) and CoMFA(Comparative Molecular Field Analysis) were both performed and four statisticallyreliable models were established: for Staphylococcus aureus (SDQSAR: R² = 0.942,Q_LOO²=0.910; CoMFA: R² = 0.979, Q² = 0.588); for Escherichia coli (SDQSAR: R² =0.881, Q_LOO²=0.832; CoMFA: R² = 0.835, Q_LOO²=0.523), and better predictivitywould be achieved by the combination of SDQSAR and CoMFA models. Byinterpreting these models we found that steric and electronic properties are the mostrelated factors with inhibitory effect, and the fatty acid derivative molecules whichpossessed denser atomic distribution, space volume in certain range, no steric effect insome regions, more electronic negativity of carboxyl terminal of fatty acid chains, andspecial electron cloud distribution and particular sensitivity to outer electric field weretend to display more potent antimicrobial activity. The results of this study suggestedthat the mechanism of inhibitory or bactericidal effect of fatty acids and theirderivatives against bacteria may be passing through the lipopolysaccharide andpeptidoglycan layers first and then disturbing the electron transport system at thecytoplasmic membrane. Above all, some of the fatty acid derivatives such asmonotridecanoin, gamma-linolenic acid and monoarachidonin were found to inhibitStaphylococcus aureus and Escherichia coli potently for the first time, and furtherresearch about their application would be carried out; and these QSAR models could beuseful in designing novel potent fatty acid derivatives as antimicrobial agents.