SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION OF SOME METAL COMPLEXES WITH LIGANDS CONTAINING CYCLIC MOIETIES

Abstract

The research work describes the synthesis and characterization of compounds containing cyclic and heterocyclic moieties, Phthalimide and phenyl amide compounds aiming at search of new candidates to battle with microorganisms. Thanks to metals for being the charm of medicinal and pharmaceutical chemistry since many decades. To widen this search, 15 potential ligands were synthesized. Compounds containing phthalimide moieties (HL1-HL6) were synthesized by the reaction of various anilines with phthalic anhydride. The compounds were isolated in pure form and checked by TLC and had sharp melting points. The single crystal structures of the compounds were also reported and discussed. Then the compounds were treated with metal salts e.g, Zn (II), Fe (III), Cu (II), Sb (III) and as a result thirty four new metal complexes were synthesized. Further, phenylamide derivatives (HL7-HL11) were synthesized by reacting anilines with acetic anhydride. HL12-HL15 were synthesized by reacting substituted anilines with maleic anhydride and succinic anhydride. Forty new complexes of these amides with metals e,g Zn (II), Fe (III), Cu (II) and Sb (III) have been synthesized. All of the synthesized complexes were heat, air and moisture stable, but during the synthesis moisture and air were avoided to prevent the oxidation of the compounds using standard Schlenk line and glove box techniques. The stability profile augments the link between organometallics and drug design and discovery. The purity of all synthesized compounds was conventionally monitored with the help of TLC in different solvents. All synthesized compounds and their complexes with transition metals were characterized by elemental analysis, FTIR, GC-MS, 1H and 13 C-NMR spectroscopy. The structures were finally confirmed with the help of single crystal structures. All synthesized compounds and their metal complexes were evaluated for their carbonic anhydrase inhibition, intestinal alkaline phosphatase inhibition, antileshminial, anti oxidant, cytotoxic and antibacterial activities. The results of these bioassays are also reported and discussed in detail. The phenylamide ligands showed good carbonic anhydrase inhibition, as compared to phthalimides ligands. Further, the activity was enhanced by 40-60% in case of antimony complexes but the zinc complexes have shown slightly less carbonic anhydrase inhibition. Similarly, the complexes of antimony with amide ligands have shown excellent IAP inhibitory activities, while the zinc complexes have shown a maximum potential against IAP inhibition. Although most of the compounds are found to be good antileshminial inhibitors, the results have proved that the metal complexes of Zn, Cu and especially Sb have increased activities as compared to parent free ligands. Additionally, the said complexes also showed enhanced cytotoxic activities against BHK-21 and H-157 cell lines. The antibacterial activity against Gram –ve and Gram +ve bacteria were outstanding in case of metal complexes with the phthalimide ligand HL2. Results of antibacterial screening of compounds as percent inhibition against bacteria are reported. Overall, these newly synthesized metal complexes have provided important candidates for drug discovery. These candidates may be improved to be used as drugs, having enhanced pharmacological action.