Antiproliferative Activity and DNA Interaction Studies of a Series of N4,N4-Dimethylated Thiosemicarbazone Derivatives (original) (raw)
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Journal of Chemistry
In a bid to come up with potential anticancer agents, a class of thiosemicarbazone ligands bearing substituted thiophene were synthesized followed by complexation with various Pd(II) and Pt(II) metal precursors. The ligands (E)-1-((thiophen-2-yl)methylene)thiosemicarbazide (L1), (E)-1-((4-bromothiophen-2-yl)methylene)thiosemicarbazide (L2), and (E)-1-((5-bromothiophen-2-yl)methylene)thiosemicarbazide (L3) were synthesized by condensation reactions and obtained in good yields. Complexation of L1 and L2 with Pd(cod)Cl2 gave C1 (C6H7Cl2N3PdS2) and C2 (C6H6BrCl2N3PdS2), respectively. Complexation of L1 with K2PtCl4 gave C3 (C6H7Cl2N3PtS2), while L3 with K2PtCl2[(PPh)3]2 gave C4 (C24H21BrClN3PPtS2). The structures and coordination for all compounds were established by FTIR, 1H-NMR, 13C-NMR, UV-Vis, elemental analysis, and single-crystal X-ray diffraction studies for ligand L1. Tuning of the spectral and anticancer activity of the compounds was investigated by changing the position of the...
Bioorganic & Medicinal Chemistry, 2008
The paper describes synthesis of several novel thiosemicarbazone derivatives. Furthermore, crystal and molecular structure of 4-diethylamino-salicylaldehyde 4-phenylthiosemicarbazone revealed planarity of conjugated aromatic system, which suggested the possibility of DNA binding by intercalation, especially for here studied naphthalene derivatives. However, here presented DNA binding studies excluded this mode of action. Physicochemical and structural properties of novel derivatives were compared with previously studied analogues, taken as reference compounds, revealing distinctive differences. In addition, novel thiosemicarbazone derivatives (1, 2 and 5-8) clearly display stronger antiproliferative activity on five tumor cell lines than the reference compounds 3 and 4, which supports their further investigation as potential antitumor agents.
2021
N(4) modified copper thiosemicarbazones have been extensively studied for their anticancer potency toward various cancer cells as they exhibit less toxicity, wide spectrum of activity, non-resistance behavior and a novel mechanism of action as compared to that of platinum complexes. 5-Nitroisatin -4-thiomorpholinyl-3-thiosemicarbazone(L1), 5nitroisatin -4, 4-dimethyl-3-thiosemicarbazone(L2), and their copper (II) complexes; CuL1 and CuL2 were prepared and characterized by elemental analysis, FTIR, NMR, ESI-HRMS, UV-Vis, TGA, PXRD (Le Bail fitting) and EPR techniques. PXRD analysis suggested that the copper (II) complexes possess a monoclinic crystal system with P1211 symmetry. The coordination of Cu(II) ion with thiosemicarbazones and one chloride ion suggests a distorted square planar geometry of complexes. All the compounds were screened against breast cancer (MCF-7 and MDA-MB231), skin cancer (A431) and normal prostate cell line (PNT2) in terms of cell viability and found that al...
2011
Complexes [Pt(2Bz4oT)Cl], [Pt(2Bz4mT)Cl], and [Pt(2Bz4pT)Cl] were prepared with N(4)-ortho-(H2Bz4oT), N(4)-meta-(H2Bz4mT), and N(4)-para-(H2Bz4pT) tolyl-2-benzoylpyridine-derived thiosemicarbazones. The thiosemicarbazones exhibited moderate anti-proliferative activity against HepG2 (hepatoma) and UACC-62 (melanoma) cancer cell lines, but showed high anti-proliferative effect against A431 (epithelial carcinoma) cancer cell lines. Upon coordination to platinum(II) the anti-proliferative activity decreases in all cases. The cytotoxicity of the previously prepared palladium(II) analogues [Pd(2Bz4oT)Cl], [Pd(2Bz4mT)Cl], and [Pd(2Bz4pT)Cl] was also investigated. As in the case of the platinum(II) complexes, coordination to palladium(II) did not lead to activity improvement. Investigations on the mechanism of cytotoxic action against A431 cells revealed that [Pd(2Bz4oT)Cl] induced DNA fragmentation and apoptosis while H2Bz4oT did not present this effect. The high anti-proliferative effect of the thiosemicarbazones and [Pd(2Bz4oT)Cl] against A431 cells, together with the pro-apoptotic effect of [Pd(2Bz4oT)Cl] suggests that these compounds have potential as chemotherapeutic drug candidates.
Cancer is undoubtedly one of the main health concerns facing our society and one of the primary targets regarding medicinal chemistry. Thiosemicarbazones and their metal complexes are compounds that possess antitumor, antibacterial, antifungal and antiviral properties. In this study, a series of copper complexes of 2anilinophenyisothiocyanate semicarbazone has been prepared and phyico-chemical characterized by elemental analysis, infrared spectroscopy (IR), Electronic spectra, magnetic moment, molar conductance measurements and X-ray diffraction pattern. The IR data before and after γ-irradiation revealed that the ligand behaves as neutral, monobasic bidentate coordination of copper ion via the carbonyl group or enolic oxygen group, NH group and thiol sulphr atom group in complex B 2. The molar conductance data revealed that the chelates are nonelectrolytes. From the spectra and magnetic moment data, the complexes were found to have square planar geometrical structures. The antitumor activities of these compounds were investigated against solid tumor induced in mice by injection of Ehrlich Ascites Carcinoma (EAC) cell line. Results revealed that tested compounds significantly reduced the tumor size. Gamma-irradiated compounds showed potent antitumor activities when compared to that of non-irradiated compounds. In addition, tested compounds exhibited stimulatory effect on the level of catalase and superoxide dismutase activities and glutathione content in liver of tumor bearing mice, while the level of lipid peroxidation was significantly reduced. It is concluded that thiosemicarbazone complexes and lignad are considered as promising anticancer drugs candidate. Moreover, the γ-irradiation evokes the antitumor activity of the tested compounds.
Molecules
Four new complexes (Ni2+, Cu2+, Ag+, and Hg2+) were prepared from the ligand N-(4-chlorophenyl)-2-(phenylglycyl)hydrazine-1-carbothioamide (H2L). Analytical and spectroscopic techniques were used to clarify the structural composition of the new chelates. In addition, all chelates were tested against bacterial strains and the HepG2 cell line to determine their antiseptic and carcinogenic properties. The Ni(II) complex was preferable to the other chelates. Molecular optimization revealed that H2L had the highest reactivity, followed by Hg-chelate, Ag-chelate, Ni-chelate, and Cu-chelate. Moreover, molecular docking was investigated against two different proteins: the ribosyltransferase enzyme (code: 3GEY) and the EGFR tyrosine kinase receptor (code: 1m17).
Oncology Letters, 2017
A series of N(4)-substituted thiosemicarbazones (TSCs) bearing pyrrole unit (1a-1e) were synthesized and fully characterized by elemental analyses, infrared spectra, 1 H nuclear magnetic resonance and single crystal X-ray diffraction. The compounds were assessed as potential chemotherapeutic agents. All newly synthesized compounds were screened for their anticancer activity against lung cancer PC-9, esophageal cancer Eca-109 and gastric cancer SGC-7901 cell lines. The results of MTT, Terminal deoxynucleotidyl transferase dUTP nick end labeling and fluorescence-activated cell sorting assays indicated that all the prepared compounds exhibited cytotoxicity against PC-9, Eca-109 and SGC-7901 cells in vitro. All the compounds significantly induced cancer cell apoptosis accompanied by increasing the Bax/Bcl-2 ratio and activation of caspase-3. The structure-activity association was discussed and the potential pre-clinical trials may be conducted. The present findings have a great potential in biomedical applications of novel N(4)-substituted TSCs.