Enhancement in anti-tubercular activity of indole based thiosemicarbazones on complexation with copper(I) and silver(I) halides: Structure elucidation, evaluation and molecular modelling

A series of monomeric tetrahedral complexes of stoichiometry, [MX(HL)(Ph3P)(2)] (In case of M = Cu, (HL)-L-1, X = I, 1; Br, 2; Cl, 3; (HL)-L-3, X = I, 4; Br, 5; Cl, 6; (HL)-L-4, X = I, 7; Br, 8; Cl, 9 and in case of M = Ag, (HL)-L-1, X = Cl, 13; Br, 14; (HL)-L-2, X = Cl, 15, Br 16; (HL)-L-3, X = Cl, 17, Br, 18) were synthesized by the reaction of copper (I) or silver (I) halides with indole-3-thiosemicarbazone ((HL)-L-1) or 5-methoxy indole-3-thiosemicarbazone ((HL)-L-2) or 5-methoxy indole-N-1 methyl-3-thiosemicarbazone ((HL)-L-3), whereas dimers of stoichiometry, [Cu-2(mu-X)(2)(eta(1)-S-(HL)-L-2)(2)(Ph3P)(2)] (X = I, 10; Br, 11; Cl, 12) were obtained by the reaction of copper (I) halides with indole-N-1-methyl-3-thiosemicarbazone (Hlntsc-N-1-Me, (HL)-L-2). The synthesized complexes were characterized using NMR (H-1 and C-13) and single crystal X-ray diffraction ((HL)-L-2, 3, 7, 8, 10, 11 and 13) as well as elemental analysis. Anti- M. tuberculosis activity of ligands ((HL)-L-1-(HL)-L-4) and their metal complexes (1-18) were evaluated against M. tuberculosis H37RV strain ATCC 27294. It has been observed that there is unusual enhancement in anti TB activity of these ligands on complexation with copper (I) and silver (I). Molecular modelling studies in the active binding site are also giving complementary theoretical support for the experimental biological data acquired.