QSAR analysis of salicylamide isosteres with the use of quantum chemical molecular descriptors.
Quantitative relationships between the molecular structure and the biological activity of 49 isosteric salicylamide derivatives as potential antituberculotics with a new mechanism of action against three Mycobacterial strains were investigated. The molecular structures were represented by quantum chemical B3LYP/6-31G( *) based molecular descriptors. A resulting set of 220 molecular descriptors, including especially electronic properties, was statistically analyzed using multiple linear regression, resulting in acceptable and robust QSAR models. The best QSAR model was found for Mycobacterium tuberculosis (r(2)=0.92; q(2)=0.89), and somewhat less good QSAR models were found for Mycobacterium avium (r(2)=0.84; q(2)=0.78) and Mycobacterium kansasii (r(2)=0.80; q(2)=0.56). All QSAR models were cross-validated using the leave-10-out procedure.
Department of Inorganic and Organic chemistry, Charles University, Heyrovského 1203, Hradec Králové 50003, Czech Republic.
R
R
Dolezal
S
S
Van Damme
P
P
Bultinck
K
K
Waisser
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D015394:Molecular Structure; D009161:Mycobacterium / Q000187:drug effects*; D009162:Mycobacterium avium / Q000187:drug effects; D021281:Quantitative Structure-Activity Relationship; D012457:Salicylamides / Q000737:chemistry* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D012457:Salicylamides; C031060:salicylamide