Chemico-Biological Interactions 2015-10-05

Pyrazolone incorporating bipyridyl metallointercalators as effective DNA, protein and lung cancer targets: Synthesis, characterization and in vitro biocidal evaluation.

Komal M Vyas, R V Devkar, Akhilesh Prajapati, R N Jadeja

Index: Chem. Biol. Interact. 240 , 250-66, (2015)

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Abstract

Pyrazolone based metal complexes have strong bio-activity but the anti-cancer mechanism of these derivatives is not fully understood. In recent years, Cu(II) complexes have attracted the interest of researchers increasingly because of their high antitumor activities that are usually related to DNA binding. The reaction of three different derivatives (I) PPMP [3-methyl-1-phenyl-4-propionyl-1H-pyrazol-5(4H)-one], (II) TMCPMP [1-(3-chlorophenyl)-3-methyl-4-(4-methylbenzoyl)-1H-pyrazol-5(4H)-one] and (III) PPTPMP [3-methyl-4-propionyl-1-p-tolyl-1H-pyrazol-5(4H)-one] of 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one and 2.2' bipyridyl along with Cu(NO3)2·3H2O under methanolic condition allowed us to isolate and characterize a series of new mixed ligand complexes [Cu(TMCPMP) (Bipy)NCS] (1) [Cu(PPMP) (Bipy)NCS] (2) and [Cu(PPTPMP) (Bipy)NCS] (3). All complexes are well characterized by elemental analysis, metal estimation, molar conductivity, FT-IR and UV-Vis spectroscopy. The molecular geometry of these complexes has been determined by single crystal X-ray study. The single-crystal X-ray structures of complexes 1 and 2 exhibit square pyramidal geometry, while complex 3 revealed slightly distorted square-pyramidal geometry. The DNA binding of these compounds with Calf-Thymus DNA (CT-DNA) has been explored by emission titration methods, which revealed that 1-3 could interact with CT-DNA through intercalation mode. The complexes also exhibited a strong binding with Bovine Serum Albumin (BSA) over the ligands. Complexes were evaluated for their in vitro cytotoxic activities against lung cancer cell lines (A549) as well as noncancerous rat cardiomyocytes (H9C2) cell lines, which showed that all three complexes exhibited substantial cytotoxic activity with minimum effect on noncancerous cells. Complex 1 with more hydrophobic environment exhibited relatively high cytotoxic activity towards A549 cells. In summary, this new series of compounds belongs to a class of copper-pyrazolonate complexes that target many biochemical sites and with potential anti-cancer activity. All these results collectively suggested that complexes could serve as promising pharmacologically active substance against lung cancer. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.