Present work deals with synthesis and biological evaluation of Cu(II), Ni(II), Zn(II) and Co(II) metal complexes derived from chlorthalidone condensed with trihydroxybenzaldehyde as potent inhibitors of dihydrofolate reductase (DHFR) from Pneumocystis carinii (pc). Structural characterizations were performed using 1H and 13C NMR, MASS, IR, UV-Vis spectrometer and elemental analysis; designed compounds were then evaluated by enzyme assay against dihydrofolate reductase of P.carinii. The Cu(II) was found to be remarkably selective inhibitor of Pneumocystis carinii DHFR. Other ligand and metal complexes exhibited moderate activity. This study shows that benzenesulfonamide moiety increases the potency of the compounds which further increases on coordination with metal ions.
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