Pharmacophore hybrid approach of new modulated bis-diimine Cu(II)/Zn(II) complexes based on 5-chloro Isatin Schiff base derivatives: Synthesis, spectral studies and comparative biological assessment

Abstract

Novel bioactive 5-chloro isatin based Schiff base ligands, (N,N'E,N,N'Z)-N,N'-(5-chloroindoline-2,3-diylidene)bis(5-nitrobenzo [d]thiazol-2-amine), L(1) and (N,N'E,N,N'Z)-N,N'-(5-chloroindoline-2,3-diylidene)bis(5-nitrothiazol-2-amine), L(2) derived from 2-amino 5-nitrobenzothiazole and 2-amino 5-nitrothiazole and their metal complexes, [Cu(L(1))2]Cl2;1, [Zn(L(1))2(H2O)2]Cl2;2, [Cu(L(2))2]Cl2;3 and [Zn(L(2))2(H2O)2]Cl2;4 have been synthesized. The composition, stoichiometry and geometry of the proposed ligands and their complexes have been envisaged by the results of elemental analyses and spectroscopic data (FT-IR, (1)H NMR and (13)C NMR, Mass and EPR). The molar conductivity values of the metal complexes revealed their ionic nature. The thermal stability of metal complexes was demonstrated by TGA/DTA studies while the crystalline nature of the complexes has been ascertained by XRD. Furthermore, a comparative account of in vitro antibacterial study against different bacterial strains with respect to standard antibiotic and scavenging activity against standard control at different concenterations unfolded pronounced antibacterial and radical scavenging potencies of the metal complexes as compared to free ligands. In addition, in vitro cytotoxicity of ligands and its metal complexes was also screened on MCF7 (Human breast adenocarcinoma), HeLa (Human cervical carcinoma) and HepG2 (Human Hepatocellular carcinoma), cell lines and normal cells (PBMC). The antiproliferative outcomes revealed that metal complexes exhibit superior activity in general as compared to free ligands (L(1) and L(2)) where metal complexes (1 and 2) of 5-chloro isatin linked benzothiazole motif (L(1)) are found to have better prospect of acting as chemotherapeutic agents which can be explained in terms of greater biopotency, planarity and conjugation against all the tested cancer cell lines with IC50<2.80 μM.

Keywords: 5-Chloro isatin; In vitro cytotoxicity; Schiff base; TGA\DTA; XRD.