A molecular modeling and QSAR study of suppressors of the growth of Trypanosoma cruzi epimastigotes.
In this work, we have used molecular modeling and QSAR tools to study 18 dithiocarbamate suppressors of the growth of Trypanosoma cruzi epimastigotes, which have been reported in the literature as superoxide dismutase (SOD) inhibitors. The principal component analysis (PCA) showed that the descriptors superficial area, heat of formation, logarithm of the partition coefficient, charge of the nitrogen atom from the dithiocarbamate group and Charges of the two carbon atoms adjacent to that nitrogen are responsible for the classification between the higher and lower trypanomicid activity. Using multiple linear regression (MLR) and docking methods it was possible to identify the probable bioactive isomers that suppress of the growth of T. cruzi epimastigotes. Our best partial least square (PLS) model obtained with these six descriptors yields a good correlation between experimental and predicted biological activities and compares two different SODs as possible target for interaction with the dithiocarbamates.
Instituto de Física de São Carlos, Universidade de São Paulo, Caixa Postal 369, Brazil. catff@terra.com.br
Carlos Henrique Tomich
CH
de Paula da Silva
Sergio Marcos
SM
Sanches
Carlton Anthony
CA
Taft
D000595:Amino Acid Sequence; D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D025341:Principal Component Analysis; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D012044:Regression Analysis; D016415:Sequence Alignment; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013859:Thiocarbamates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development*
D004791:Enzyme Inhibitors; D013859:Thiocarbamates; D013482:Superoxide Dismutase