Physicochemical, in-vitro therapeutic activity and biomolecular interaction studies of Mn(II), Ni(II) and Cu(II) complexes tethered with O2N2 ligand backbone.

Two major health crisis of today's world are antimicrobial drug resistance and type II diabetes. To tackle them, there is an immediate requirement for the development of new and safer drugs and the present work is one such quest for novel and efficient drug candidates. We have developed three trace metal coordination compounds tethered with a reduced salen ligand {H2(hpdbal)2-an} (L), namely, a manganese-salan complex, [MnII(H2O)2{(hpdbal)2-an}] (1), a nickel-salan complex, [NiII{(hpdbal)2-an}] (2) and a copper-salan complex, [CuII{(hpdbal)2-an}] (3). The compounds were characterized by elemental analysis, vibrational spectroscopy, electronic spectroscopy, thermogravimetric analysis, nuclear magnetic resonance and electron-paramagnetic resonance techniques. The compounds were evaluated for antimicrobial activity against seven pathogens (Escherichia coli, Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans and Cryptococcus neoformans) and antidiabetic activity by mimicking diabetic environment on the immortal human liver cancer cells, HepG2. Complexes 1 and 2 were additionally tested for their reactivity and stability in biological media mimic conditions. The nickel(II) salan complex (2) exhibited noteworthy antifungal activity against Candida albicans and the manganese(II) salan complex (1) induced increased glucose uptake by the insulin resistant cells. Both compounds were found to be stable when solution pH conditions were varied from 3 to 9. They exhibited strong affinity of binding towards a carrier protein, bovine serum albumin which was evaluated with the aid of multi-spectroscopic techniques.

Potent drug candidature of an ONS donor tethered copper (II) complex: Anticancer activity, cytotoxicity and spectroscopically approached BSA binding studies.

In our continued efforts to develop metal based therapeutic agents, we have synthesized a novel copper(II) complex, [{Cu(hpdbal-sbdt)}2] (2) tethered with a biocompatible ONS2- donor backbone [H2hpdbal-sbdt] (1) [H2hpdbal-sbdt is a tridentate ligand derived from S-benzyldithiocarbazate (Hsbdt) and 2-hydroxy-5-(phenyldiazenyl)benzaldehyde (Hhpdbal)]. The metal complex (2) was characterized using attenuated total reflection-infrared (ATR-IR) spectroscopy, electron paramagnetic resonance (EPR) spectroscopy, thermogravimetry and differential scanning calorimetric (TG-DSC) analysis, field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDS) and elemental (CHNS) analysis. The antineoplastic ability of copper complex was evaluated in vitro against human cervical cancer (HeLa) cells. MTT assay results showed that the copper complex exhibited significant growth inhibition of HeLa cells with an IC50 value of 4.46 µM and this value was compared with reported standards. Cytotoxicity of the copper complex towards human embryonic kidney cells (HEK-293) was also evaluated. The potentially active copper complex was studied for its solution state stability at a pH range of 3-9. Following this, the interactive behaviour of the bioactive copper complex with a drug transporter protein (BSA) was deciphered through multi-spectrosopic investigations like steady-state fluorescence, three-dimensional fluorescence, deconvoluted-IR and UV-Visible techniques.