An-Najah Staff

A computation model has been developed for the rational design of bioactive
pharmacophore sites as anti-Mycobacterium Tuberculosis (MT) 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-Trypanosoma cruzi (TC)
activity is obtained for compounds 8 and 18 which exhibited low IC50 values (9.2 and 10.8
M), almost equal to clinical drug, Nifurtimox (7.7 M; 100% Inhib.). This could be
attributed to the existence of two synergic (O---N-) and (O---O-) anti-Tryposomal
phramacophore sites. In contrast to compounds 8 and 18 which contain electro-attractor
groups (R1, R2 = F), analogue compounds 1 and 13 with electro-donor or only hydrogen (R1,
R2 = CH3, H) shows best antibacterial activity (MIC = 0.977 and 1.190 g/mL) very close to
antitubercular activity of Rifampicin (MIC = 0.125 g/mL). This could be attributed to the
existence of (O---NH+) antibacterial phramacophore site.