Anti-Cancer Screening of Some Transition Metal Ion Complexes with Coumarin Derivatives (original) (raw)
Related papers
Novel transition metal Cu(II), Ni(II), Co(II) and Zn(II) ions complexes of bidentate Schiff base ligand obtained from 4-Methyl 7-hydroxy 8-formyl coumarin, and Dimethylamino propylene diamine have been prepared and characterized by physical, spectral and analytical data. The synthesized Schiff base act as bidentate ligand for the complexation reaction with Cu(II), Ni(II), Co(II) and Zn(II) ions. The new compounds, possessing the general formula [M(L) 2 .2H 2 O] where [M= Cu(II), Ni(II), Co(II) and Zn(II)] show octahedral geometry. In order to evaluate the effect of metal ions upon chelation, the Schiff base and their metal complexes have been screened for antimicrobial activity. The transition metal complexes have shown enhanced antimicrobial activities as compared to Schiff base.
CHEMICAL & PHARMACEUTICAL BULLETIN, 2010
Regular Article Currently, cancer is the second cause of death, accounting for about a quarter of all deaths. Nearly one half of all cancers that are diagnosed result in the death of the patient, so that the development of new anticancer therapies is one of the fundamental goals in medicinal chemistry. Coumarin (1,2-benzopyrone) is structurally the least complex member of a class of compounds known as benzopyrones. 1) Nowadays, Coumarins have long been recognized to possess anti-inflammatory, antioxidant, antithrombotic, antiallergic, hepatoprotective, antiviral and anticarcinogenic activities. 2-5) Regarding their high fluorescence ability, they are widely used as fluorescent probes in biology and medicine. 6,7) More recently, coumarin derivatives have been evaluated in the treatment of human immunodeficiency virus, due to their ability to inhibit human immunodeficiency virus integrase. 8,9) Interest in metal coumarin complexes has arisen from the search for novel lead compounds along with the desire to improve the pharmacological profile. For example, some interesting lanthanide complexes of coumarin derivatives like bis(4-hydroxy-3-coumarinyl) acetic acid, 10) the ligand 8,8Ј-[1,2-ethanediylbis(nitriloethylidyne)]bis[7-hydroxy-4-methyl-2H-1-benzopyran-2-one] and coumarin-3-carboxylic acid have been reported. 11-13) Transition metal complexes with coumarin Schiff bases have also been reported recently. 14,15) 1,10-Phenanthroline (phen) and substituted derivatives, both in the metal-free state and as ligands coordinated to transition metals, disturb the functioning of a wide variety of biological systems. 16) Copper complexes of 1,10phenanthroline and its derivatives are of great interests since they exhibit numerous biological activities such as antitumor, anti-Candida, antimycobacterial and antimicrobial activity etc. 17-20) Moreover, considerable attention has been focused on the use of phenanthroline complexes as intercalating agents of DNA and as artificial nucleases. 21-24) Amino acids are the basic structural units of proteins, and some copper complexes of amino acids were reported to exhibit potent antitumor and artificial nuclease activity. 25,26) In this context, we focused our interests on the development of ternary copper(II) complexes of amino-coumarins with phenanthroline, and investigated their in vitro cytotoxicity. We report here the preparation of two novel ternary copper(II) complexes of amino-coumarins with phenanthroline. The selection of 7-hydroxyl-4-methyl coumarine as a second ligand in the ternary copper(II) complexes may enhance the affinity of the complex towards DNA because of the formation of hydrogen bonds between the hydroxyl group of 7-hydroxyl-4-methyl coumarine and DNA double helix and increase the biocompatibility of the complex. 27) Experimental Materials 7-Hydroxy-4-methyl coumarine, calf thymus DNA (ct DNA) and ethidium bromide (EB) were obtained from Sigma Chemical Co. All the experiments involving interaction of the complexes with ct DNA were carried out in doubly distilled water buffer containing 5 mM Tris[Tris(hydroxymethyl)aminomethane] and 50 mM NaCl, and adjusted to pH 7.2 with hydrochloric acid. The concentration of DNA solution was determined from UV absorption at 260 nm using a molar absorption coefficient e 260 ϭ6600 mol Ϫ1 cm Ϫ1. Purity of the DNA was checked by monitoring the ratio of the absorbance at 260 nm to that at 280 nm. The solution gave a ratio of A 260 / A 280 Ͼ1.80, indicating that DNA was sufficiently free from protein. 28) Physical Measurements The UV-Vis absorption measurements were conducted by using a Varian Cary 100 spectrophotometer equipped with quartz cells. All fluorescence emission spectra were measured using a Hitachi F-4500 spectrofluorophotometer equipped with a xenon lamp source and a quartz cell of 1 cm path length. Viscosity experiments were carried out on an Ubbelodhe viscometer. The circular dichroism (CD) spectra were recorded on a Jasco J-810 spectropolarimeter. The elemental analyses were performed in the microanalytical laboratory, Department of Chemistry, National University of Singapore. The 1 H-NMR spectra were recorded with a Bruker ACF300 FT-NMR instrument using tetramethylsilane (TMS) as an internal reference in D 2 O for the ligand. Electrospray ionization (ESI) mass spectra were recorded on a Finnigan MAT LCQ mass spectrometer using the syringe pump method. Methods Absorption titration experiments were performed by fixing
Journal of …, 2009
Novel complexes of Ni(II), Co(II), and Cu(II) were synthesized with the macrocyclic ligand, i.e., 5,8,13,16-tetraoxo-1,4,9,12-tetraazacyclohexa-decane. The ligand was prepared by the [2+2] condensation of succinic acid and ethylenediamine. Synthesized complexes have been characterized based on elemental analysis, FTIR, 1 H NMR, ESI MS, TG/DTA, UV-Vis spectroscopic techniques, conductivity and magnetic measurements. The molar conductance measurements of Cu(II), Co(II) and Ni(II) complexes in DMF correspond to non electrolyte nature. The redox properties of the complexes were extensively investigated by electrochemical method using cyclic voltammetry (CV). Based on these studies, a six coordinate octahedral geometry around the metal ions in the complexes has been proposed. These metal complexes were also tested for their in vitro antimicrobial activities against some bacterial and fungal strains to assess their inhibiting potential and the activities shown by these complexes were compared with standard drugs.
IOSR Journal of Applied Chemistry, 2013
7-hydroxy-4-methyl-8-(p-methylphenylazo)coumarin (L1) and 7-hydroxy-4-methyl-8-(pmethoxyphenylazo)coumarin (L2) have been prepared and characterized by elemental analysis, infrared (IR), proton nuclear magnetic resonance (1 H NMR) and mass spectra. The important infrared (IR) spectral bands corresponding to the active groups in the two ligands and the solid complexes under investigation were studied. Also the important fragments in the ligands and complexes were done using mass spectra and the main peaks were corresponding to the molecular weights of the ligands and complexes. The solid complexes have been synthesized and characterized by elemental and thermal analyses (TG and DTA) as well as by IR, 1 H NMR, magnetic measurements, electronic transition, molar conductance, mass and electron spin resonance (ESR) spectra. The proposed steriochemical structures for the investigated metal complexes suggest octahedral geometry with respect to Mn, Co, Ni, Cu and Zn divalent metal ions with the investigated ligands 1:1 and 1:2 complexes and all of the formed complexes contain coordinated and hydrated water molecules. All of the prepared solid complexes behave as non-electrolytes in chloroform.
Dalton Transactions, 2010
The coordination modes of copper(II) complexes of Schiff base-derived coumarin ligands, which had previously shown good anti-Candida activity, were investigated by pH-potentiometric and UV-Vis spectroscopic methods. These studies confirmed the coordination mode of the ligands to be through the N of the imine and deprotonated phenol of the coumarin-derived ligand in solution. In addition, the more active complexes and their corresponding ligands were investigated in the presence of copper(II) in liquid and frozen solution by ESR spectroscopic methods. A series of secondary amine derivatives of the Schiff base ligands, were isolated with good solubility characteristics but showed little anti-Candida activity. However, cytotoxicity studies of the secondary amines, together with the copper complexes and their corresponding ligands, against human colon cancer and human breast cancer cells identified the chemotherapeutic potential of these new ligands. Structures of Schiff bases 1a-1k and their corresponding secondary amines 3a-3k showing the numbering system used in the assignment of 1 H and 13 C NMR spectra.
Archiv Der Pharmazie, 2001
Carboxylate ligands are widely used in chemistry and pharmacy owing to their ability to form stable complexes with a large variety of metal ions. In that context, carboxylate complexes allow modulation of the pharmaceutical products. Herein, a series of six novel Zn(II) carboxylates: [Zn(L 1) 2 ] (1), [Zn(L 1) 2 (bipy)] (2), [Zn(L 1) 2 (phen)] (3), [Zn(L 2) 2 ] (4), [Zn(L 2) 2 (bipy)] (5) and [Zn(L 2) 2 (phen)] (6) (where L 1 = 4-(2-methoxy-5-nitrophenylamino)-4-oxobutanoic acid), L 2 = 4-(2-nitro-4-methoxyphenylamino)-4-oxobutanoic acid), phen = 1,10-phenanthroline and bipy = 2,2′-bipyridine) were synthesized in good yield and successfully characterized by 1 H, 13 C NMR, FT-IR and single-crystal X-ray crystallography. The spectroscopic data reveal that the absence of OH peak in the spectra of complexes confirm their formation. Single-crystal X-ray crystallographic data for complexes 1 and 5 show a distorted octahedral environment around the Zn atom. The results of both FT-IR and single-crystal X-ray crystallography confirm the bidentate nature of the carboxylate ligands. The DNA interaction study of the synthesized complexes was investigated using UV-visible spectroscopy and viscosity measurements suggesting an intercalative binding mode of interaction of the complexes with SS-DNA. The interaction between the synthesized complexes and CTAB was elaborately studied with a conductometric method. The conductivity method was used to find CMC, higher CMC values suggesting a stable complex-CTAB system. Results of in vitro antibacterial and antifungal activities indicate the biological potency of the synthesized compounds.
New zirconium (IV) complexes of coumarins with cytotoxic activity
European Journal of Medicinal Chemistry, 2006
Complexes of zirconium (IV) with some bis-coumarin ligands have been synthesized. The zirconium (IV) complexes with bis-coumarins were characterized by different physicochemical methods-elemental analysis, IR-, and 1 H-NMR-spectroscopies and mass spectral data. The spectral data of zirconium (IV) complexes were interpreted on the basis of comparison with the spectra of the free ligands. The results of the ligands and their complexes, based on spectral data are informative and useful for suggestion of the metal-ligand binding mode. Cytotoxic screening by MTT assay was carried out. In the present study we performed comparative evaluation of the cytotoxic effects of the three newly synthesized zirconium complexes against the acute myeloid leukemia derived HL-60 and the chronic myeloid leukemia LAMA-84. The preliminary cytotoxicity screening program revealed that the investigated zirconium complexes induced 50% inhibition of the cell viability of HL-60 and LAMA-84 cells at micromolar concentrations and thus could be considered as biologically active. Independently of the tumor test system evaluated the complex of bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-(1H-pyrazol-3-yl)-methane proved superior to the remaining agents with respect to the IC 50 values obtained. The complexes of both the other coumarins evaluated proved to be less potent than the corresponding free ligands, as evidenced by the IC 50 values obtained. Thus the zirconium complexes with coumarin ligands represent a novel class of antiproliferative agents, which deserve further attention in search of anticancer lead compounds.
New metal complexes of 4-methyl-7-hydroxycoumarin sodium salt and their pharmacological activity
Complexes of copper (II), zinc (II), nickel (II), cobalt (II) and iron (III) with 4-methyl-7-hydroxycoumarin sodium salt (Mendiaxon, Hymecromone) were synthesized by mixing of equimolar amounts of the respective metal nitrates and 4-methyl-7-hydroxycoumarin sodium salt in water. The complexes were characterized and identified by elemental analysis, conductivities, IR, 1 H NMR spectroscopy and mass spectral data. DTA and TGA have been applied to study the compositions of the compounds. Thermal analysis of the complexes indicate the formation of compounds which correspond to the compositions Met(HL) 2 ·nH 2 O, where Met = Cu, Zn, Ni, Co; n= 2, 3 or 4 and Fe(HL) 3 ·5H 2 O. The newly synthesized compounds were assayed for acute intraperitoneal and per oral toxicity, influence on blood clotting time and the most active complex was investigated for spasmolytic activity.