Synthesis and In-Vitro Study of some Transition Metal Complexes of Novel Heterocyclic Schiff Bases as Potential Anti-Tuberculosis Agents

Dueke-Eze, C.U (2015-04)

A Thesis Submitted to the School of Postgraduate Studies, University of Lagos


The increasing reports of resistance of Mycobacterium tuberculosis (M.TB) to the classical anti-tuberculosis drugs pose a challenge to effective control of M.TB. This drug resistance has led to renewed interest in the search for new classes of compounds active against M.TB. Novel Schiff bases were obtained by the condensation reaction of 2-hydroxybenzaldehyde (salicylaldehyde), 5-nitro-2-hydroxybenzaldehye (5-nitrosalicylaldehyde), 5-bromo-2-hydroxybenzaldehyde (5-bromosalicylaldehyde) and 5-methoxy-2-hydroxybenzaldehyde (5-methoxysalicylaldehyde) with 2-aminopyridine (L1-L4), 4-aminopyridine (L5-L7) and isonicotinic acid hydrazide (INH) (L8-L11). In addition, more INH Schiff bases were obtained by the reaction of 2-pyrrole carboxaldehyde, 2-thiophene carboxaldehyde and INH (L12-L13). These Schiff bases were reacted with CuCl2.2H2O, NiCl2.6H2O and CoCl2.6H2O to form Cu(II), Ni(II) and Co(II) complexes. The synthesized compounds were evaluated for their in-vitro anti-tuberculosis activity against a standard (M.TB H37Rv ) and clinical isolate strains using the proportion method. The compounds were characterized using melting point, infrared (IR), 1H and 13C nuclear magnetic resonance (NMR), electronic absorption, atomic absorption spectroscopy, elemental analyses and conductivity measurements. The physical data revealed that the Schiff bases were obtained in moderate to high yields. Based on the infrared and electronic absorption spectroscopic data, the geometry for the copper complexes of aminopyridines (L1A-L7A) and INH (L8A-L10A) were deduced to be square planar and octahedral respectively. With few exceptions, most of the nickel and cobalt complexes were octahedral owing to their spectral behavior. The geometries of all the complexes (L12A-L13C) containing either the pyrrole or thiophene moiety were deduced to be square planar. The copper complexes had the general formulae [MLX.H2O].nH2O (L1A-L7A and L13A) and [ML2].nH2O (L8A-L12A), the nickel complexes are of the general formulae [ML2.nH2O].nH2O (L3B-L5B), [ML2] (L6B, L7B, L12B and L13B), [ML.nH2O].X.nH2O (L8B and L9B) and [MLX.nH2O].nH2O (L10B-11B) and the cobalt complexes had the general formulae [ML2.nH2O].nH2O (L1C-L7C), [ML.nH2O].X.nH2O (L8C) and [ML2].nH2O (L9C, L12C and L13C), (M = metal, L = Schiff base, X = chlorine). The conductivity measurements reveal that all the complexes except L8B, L8C and L9B were non-electrolytes. The synthesized compounds were evaluated for their in-vitro anti-tuberculosis activity against Mycobacterium tuberculosis H37Rv and a clinical isolate. The anti-tuberculosis activity of most of the Schiff bases increased with the presence of metal ion. The copper and cobalt complexes of the pyrrole and nitro-containing compounds exhibited significant activity when compared with the reference compound (INH). In addition, the cobalt complex having the thiophene moiety showed significant effect on the clinical isolate. These compounds can be considered as a good starting point to develop new novel lead compounds for the management of tuberculosis.