Abstract
A computation model has been developed for the rational design of bioactive pharmacophore sites as anti-Mycobacterium tuberculosis and anti-Trypanosoma cruzi (TC) candidates. The 40 compounds 1-40 analyzed have been previously screened for their antitubercular and antitrypanosomal activity. The highest anti-TC activity is obtained for compounds 8 and 18 which exhibited low IC50 values (9.2 and 10.8 mu M), almost equal to clinical drug, nifurtimox (7.7 mu M; 100 % Inhib.). This could be attributed to the existence of two synergic (O (delta-)-N (delta-)) and (O (delta-)-O (delta-)) antitrypanosomal pharmacophore sites. In contrast to compounds 8 and 18 which contain electro-attractor groups (R-1, R-2 = F), analog compounds 1 and 13 with electro-donor or only hydrogen (R-1, R-2 = CH3, H) show best antibacterial activity (MIC = 0.977 and 1.190 mu g/mL) very close to antitubercular activity of Rifampicin (MIC = 0.125 mu g/mL). This could be attributed to the existence of (O (delta-)-NH (delta+)) antibacterial pharmacophore site.