Combination of molecular modeling and quantitative structure-activity relationship analysis in the study of antimycobacterial activity of pyridine derivatives

A set of 4-benzylsulfanyl derivatives of pyridine-2-carbonitriles and pyrid ine-2-carbothioamides, previously tested for their antimycobacterial activi ty, were analysed by quantitative structure-activity relationship (QSAR) te chniques, using some physicochemical and quantum-chemical parameters. The r esulting QSAR revealed that the activity increases with electron withdrawin g substituents in the benzyl moiety of studied compounds. HOMO orbitals can play an important rule in the description of the mechanism of interactions at the molecular level. Additionally, the results of multiple linear regre ssion indicate the differences between Mycobacterium tuberculosis and M. av ium. The hydrophobicity of studied compounds is important for activity agai nst M. avium. (C) 2000 Elsevier Science B.V. All rights reserved.