Monodentate Coordination of N, N′‐Disubstituted Thiocarbamide Ligands: Syntheses, Structural Analyses, In Vitro Cytotoxicity and DNA Damage Studies of Cu(I) Complexes

Pandey, Sunil; Singh, Durga P.; Marverti, Gaetano; Butcher, Ray J.; Pratap, Seema

doi:10.1002/slct.201800145

Cited by 13 publications

(7 citation statements)

References 41 publications

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“…The ability of the drugs to induce either apoptosis or necrosis seems to be a primary factor in determining their anti‐cancer efficacy . The cytotoxicity of the three complexes and their ligands were determined in terms of a colorimetric microculture assay (MTT) in HeLa and KB cells, yielding IC 50 values shown in Table , which also shows the comparison of experimental conditions with the results of cisplatin experiments.…”

Section: Resultsmentioning

confidence: 99%

Structure and cytotoxicity of zinc (II) and cobalt (II) complexes based on 1,3,5‐tris(1‐imidazolyl) benzene

Zhu

Zhao

Peng

et al. 2019

Applied Organom Chemis

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Three novel complexes, [Zn (tib)2·(H2O)2]·(NO3)2 (1), [Co (tib)2]·2NO3 (2) and [Co2(tib)2(btc)]·H2O (3) [H4btc = 1,2,4,5‐benzenetetracarboxylic acid; H2tib = 1,3,5‐tris(1‐imidazolyl)benzene], were synthesized and characterized by single‐crystal X‐ray, IR and elemental analysis. The interaction of these complexes with FS‐DNA (fish sperm DNA) was monitored, and binding constants were determined using UV/Vis, which revealed that they have the ability to bind to FS‐DNA. DNA‐binding constants (K) for the three complexes were 2.2 × 104 m−1, 0.7 × 104 m−1 and 0.09 × 104 m−1, respectively. The interaction capacity of the complexes with FS‐DNA has been investigated by fluorescence spectroscopy. Stern–Volmer quenching plot values for complexes 1, 2 and 3 were 0.3784, 0.1028 and 0.076, respectively. The viscosity measurement suggested that complexes 1, 2 and 3 interact with DNA in an intercalation mode. In addition, anti‐cancer activities of these complexes investigated through MTT assays in vitro indicated that the complexes showed good cytotoxic activity against cancer cell lines. Cytotoxic activity of test complexes against two different cancer cell lines (HeLa and KB cells) showed significant cancer cell inhibition rates. Flow cytometry experiments and morphological apoptosis studies showed that the complexes induced apoptosis of HeLa tumor cell lines. Finally, a further molecular docking technique was employed to confirm the binding of the complexes toward the molecular target DNA.

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Section: Resultsmentioning

confidence: 99%

Structure and cytotoxicity of zinc (II) and cobalt (II) complexes based on 1,3,5‐tris(1‐imidazolyl) benzene

Zhu

Zhao

Peng

et al. 2019

Applied Organom Chemis

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“…Some of the important pharmacological activities ascribed to ureides are anti‐infectives, antitumor, anticancer and the various metabolic disorders include diabetes and hyperlipidemia . In a recent report by Pratap et al ., N,N′‐disubstituted thiourea molecules and their copper complexes showed moderate to potent cytotoxic properties against cervical carcinoma (2008 and C 13 ) and ovarian carcinoma (A2780, A2780/CP and IGROV‐1) cell lines. Moreover, the activities of the complexes were found to be stronger than the individual ligands and the latter have close cytotoxic properties compared to the present synthesized molecules.…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Characterization, Anticancer and Antimicrobial Activity Studies of Novel Isomeric 2,4‐Disubstituted Ureide Derivatives of Pyrimidinopiperidines

et al. 2019

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A series of isomeric ureide derivatives of novel 2,4-disubstituted pyrimidinopiperidines were synthesized starting from 2,4dichloropyrimidine. All the final products were purified on silica and characterized by spectral analysis. Both the 2,4-disubstituted pyrimidinopiperidines were analyzed for their in vitro anticancer activity on the cell lines HCT116, MIA-PaCa2 and MDA-MB 231 by using MTT cell proliferation assay. Further, the antimicrobial studies were carried out against different bacterial and fungal strains by employing cup plate method. These compounds were showed significant anticancer activity on tested three cancer cell lines and exhibited potent antimicrobial activity in tested strains of bacteria and fungi. Results and Discussion Chemistry Synthesis of ureide derivatives of 2-aryl-4-(-4-amino piperidinyl) pyrimidines (5 a-l):The reaction of 2,4-dichloro-pyrimidine (1) with tert-butylpiperidin-4-ylcarbamate in presence of diisopropylethylamine in dichloromethane at room temperature afforded the 4-substituted 2-chloropyrimidine derivative 2 a with 62% yield (Scheme 1) after purifying by column Scheme 1. Reagents and conditions: i) tert-butyl-piperidin-4yl-carbamate, DIPEA, THF, rt, 4 h; ii) R = a-d, Pd 2 (dba) 3 , X-Phos, DIPEA, rt, 18 h; iii) TFA, DCM, rt, 10 min; iv) R 1 = e-g, DIPEA, reflux, 10 min. EntryAmino piperidine derivative (4 A-4D) Isocyanate (e-g) Urea derivative (5 A-5 L) Yield (%) 6 95 7 92 8 91 9 95 10 92

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“…The in vitro cytotoxic results of copper(I) complexes of N-aryl, N'-isobutoxy/methoxycarbonyl thiocarbamide (C 106 -C 108 ) (Fig. 24) against A2780, A2780/CP, IGROV-1, 2008 (cervical), and C13* (cervical) cancer cell lines showed the higher anticancer potency than that of their coordinating ligands through the mechanism of DNA damage (Singh et al, 2015, Pandey et al, 2018. The copper complexes tend to break the strand of induced DNA via highly reactive hydroxyl radical (•OH) and superoxide anion (O 2 -) (Mosmann, 1983, Lopes et al, 1997, Lee & Steinert, 2003, Stepanenko & Dmitrenko, 2015.…”

Section: Copper(i) Complexes Of N N'-disubstituted Thioamidesmentioning

confidence: 99%

“…The presence of highly electronegative atoms or group of atoms on organic moiety has been found to cleave DNA more effectively (Shao et al, 2014, Stepanenko & Dmitrenko, 2015 so the complexes C 105 and C 106 showed significant anticancer effect toward IGROV-1, 2008 (cervical) and C13* (cervical) cell lines. (Singh et al, 2015, Pandey et al, 2018 A unique copper(I/II) complex of hydroxyl naphthalene derivative…”

Section: Copper(i) Complexes Of N N'-disubstituted Thioamidesmentioning

confidence: 99%

“…The thiocarbamides with two different substituents on Natoms exhibit hydrogen bonding between the carbonyl group of substituent and HN group of amide that helps the existence of coordinate covalent bond directly through Satoms, increases lipophilicity and anticancer potency of ligands and their complexes via effective interaction with DNA (Xian et al, 2004;Saeed et al, 2010;Singh et al, 2015;Saswati et al, 2015;Mahendiran et al, 2018b;Pandey et al, 2018). Copper(I) ion, obtained by the reduction of copper(II) ion with metallo-reductase at the cell surface of living organisms, before uptake into the cell can be transported into the living cells by their specific transporters Marzano et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Anticancer Potency of Copper(I) Complexes Against a Range Cancer Cell Lines: A Review

Singh

Yadav

2021

J. Inst. Sci. Tech.

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The copper(I) complexes of N,N-diimine, N,O- and/or N, S-bidentate systems perform significant dose-dependent anticancer activity toward various cell lines viz. MCF-7, LNCap, PSN-1, A431, BxPC3, H157, A2780, HeLa, MDA-MB231, MGC-803 etc. The copper(I) complexes can cross the cellular plasmalemma that results in the accumulation of copper ion in the cancer cells, exhibit significant anticancer effect and overcome the multidrug resistance because these can slightly induce the DNA cleavage as a result of limited generation of reactive oxygen species (ROS). Copper(I) complexes exhibit significantly higher broad-spectrum antiproliferation and cell apoptosis via mitochondrial pathway than that of their corresponding Cu(II), Co(II), Pd(II), and Ni(II) complexes. The copper(I) complexes inhibit the cancer cells not only via ROS generation but also via DNA interactions possibly by attacking the sugar-phosphate backbone of DNA due to their oxidative and partial dissociation behavior. Copper(II/I) complexes are also able to cleave DNA by hydrolytic pathway and induce caspase-dependent-mitochondrial-mediated cell apoptosis by ROS production or blocking the progression of cell cycles. In many cases, the modification in organic moiety and the placement of electronegative substituent near the metallic center of complexes have been found to enhance their anticancer potency in a significant manner. Thus copper(I) complexes may be used as the better anticancer drugs with multiple modes of action compared to the copper(II) complexes due to having oxidative behavior and generation of empty site on copper(I) ion during partial dissociation.

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Monodentate Coordination of N, N′‐Disubstituted Thiocarbamide Ligands: Syntheses, Structural Analyses, In Vitro Cytotoxicity and DNA Damage Studies of Cu(I) Complexes

Cited by 13 publications

References 41 publications

Structure and cytotoxicity of zinc (II) and cobalt (II) complexes based on 1,3,5‐tris(1‐imidazolyl) benzene

Structure and cytotoxicity of zinc (II) and cobalt (II) complexes based on 1,3,5‐tris(1‐imidazolyl) benzene

Synthesis, Characterization, Anticancer and Antimicrobial Activity Studies of Novel Isomeric 2,4‐Disubstituted Ureide Derivatives of Pyrimidinopiperidines

Anticancer Potency of Copper(I) Complexes Against a Range Cancer Cell Lines: A Review

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