Pyrazolone incorporating bipyridyl metallointercalators as effective DNA, protein and lung cancer targets: Synthesis, characterization and in vitro biocidal evaluation.
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.
Department of Chemistry, Faculty of Science, The M. S. University of Baroda, Vadodara 390 002, India; Institute of Infrastructure, Technology, Research and Management, Ahmedabad 380 026, Gujarat, India.
Komal M
KM
Vyas
Division of Phytotherapeutics and Metabolic Endocrinology, Faculty of Science, The M.S. University of Baroda, Vadodara 390 002, Gujarat, India.
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RV
Devkar
Department of Biochemistry, Faculty of Science, The M. S. University of Baroda, Vadodara 390 002, India.
Akhilesh
A
Prajapati
Department of Chemistry, Faculty of Science, The M. S. University of Baroda, Vadodara 390 002, India. Electronic address: rajendra_jadeja@yahoo.com.
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RN
Jadeja
D015082:2,2'-Dipyridyl / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003300:Copper / Q000737:chemistry; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy; D015394:Molecular Structure; D011485:Protein Binding; D047069:Pyrazolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D007364:Intercalating Agents; D047069:Pyrazolones; D015082:2,2'-Dipyridyl; D003300:Copper; D004247:DNA
Acyl pyrazolone; Anti-cancer activity; DNA and protein binding; Mixed-ligand Cu(II) complexes