A multifunctional molecular entity Cu<sup>II</sup>–Sn<sup>IV</sup> heterobimetallic complex as a potential cancer chemotherapeutic agent: DNA binding/cleavage, SOD mimetic, topoisomerase Iα inhibitory and in vitro cytotoxic activities

Tabassum, Sartaj; Asim, Ahmad; Khan, Rais Ahmad; Arjmand, Farukh; Dhivya, Rajakumar; Balaji, Perumalsamy; Akbarsha, Mohammad Abdulkader

doi:10.1039/c5ra07333b

Cited by 34 publications

(20 citation statements)

References 66 publications

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“…In order to accommodate the bound ligand, separation of base pairs occurs which leads to an increase in viscosity of DNA. However, partial or non‐classical intercalators could cause bending or kinking in DNA helix, which results in a reduction of its length and concomitantly, its viscosity . Furthermore, the non‐intercalators (electrostatic and grooved binder) cause a less significant change in viscosity of DNA .…”

Section: Resultsmentioning

confidence: 99%

“…Organotin complexes have been studied extensively for their ability to cleave supercoiled (SC) pBR322 DNA with the help of agarose gel electrophoresis. Cleavage of one strand results in a slower moving nicked circular (NC) form, however, cleavage of both the strands produce a linear (L) form, which is positioned between nicked and supercoiled forms, as the DNA moved under the influence of electric field. The extent of cleavage of plasmid DNA for all the complexes was analyzed with increasing complex concentration and with ascorbic acid, which acts as an activator of cleavage activity.…”

Section: Resultsmentioning

confidence: 99%

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Synthesis, characterization and binding studies of novel diorganotin(IV) complexes of sodium 2‐mercaptoethanesulfonate

Kumari

Nath

2018

Applied Organom Chemis

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Diorganotin(IV) complexes(1-4) of MESNA (sodium 2mercaptoethanesulfonate HSCH 2 CH 2 SO 3 Na) and a mixed ligand complex of dibutyltin(IV), 1,10-phenanthroline and MESNA (5) were synthesized with thermal and microwave assisted methods. All the complexes were characterized thoroughly with the help of analytical and various spectroscopic techniques viz.FTIR, NMR ( 1 H, 13 C, and 119 Sn NMR) spectroscopy and ESI-MS spectrometery.Various spectrophotometric studies were carried out to decipher the binding mode of MESNA and its diorganotin complexes 1-5 with calf thymus DNA (CT DNA) and thus, to calculate the binding constant (K b ). Absorption spectrophotometric study confirmed the interaction is through partial intercalation of all the complexes including MESNA, inside the DNA helix and calculated binding constant (K b ) is in the order of 10 3 M -1 . A series of emission spectrophotometric experiments support the results obtained through the absorption spectrophotometric studies. Circular dichroic (CD) spectroscopic analysis and viscosity measurement of CT DNA further complemented the fact that the partial intercalation plays a major role in the interaction of the studied complexes with CT DNA. All the studies corroborated that complex 2 bound to CT DNA with maximum affinity followed by complex 5 among all the complexes.Involvement of hydroxyl radicals as an active species in the cleavage activity of pBR322 plasmid DNA is proved by carrying out agarose gel electrophoretic technique.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Synthesis, characterization and binding studies of novel diorganotin(IV) complexes of sodium 2‐mercaptoethanesulfonate

Kumari

Nath

2018

Applied Organom Chemis

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“…The effect of stereochemistry on biological activity is of great importance in medicinal chemistry, as many of the biological targets are chiral [30,31]. The anticancer properties of chiral metal derivatives have been largely studied [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46], but the role of the stereochemistry in the biological activity of non-platinum based compounds has been less investigated [22,[47][48][49][50][51][52][53][54][55][56][57][58][59][60][61]. Effect of the absolute configuration on the anticancer efficiency of titanium compounds was firstly explored by Tshuva in 2010 [50].…”

Section: Introductionmentioning

confidence: 99%

Study of the anticancer properties of optically active titanocene oximato compounds

Cueva-Alique

Sierra

Pérez‐Redondo

et al. 2019

Journal of Organometallic Chemistry

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New water soluble and optically active cyclopentadienyl titanium derivatives [(η 5-C 5 H 5) 2 Ti{(1R,4S)-ĸON,(R)NH}Cl] (R = Bn (Benzyl) 1a', 2-pic (2-picolylamine) 1b') have been synthesized. The novel compounds along with those previously described [(η 5-C 5 H 5) 2 Ti{(1S,4R)-ĸON,(R)NH}Cl] (R = Bn 1a, 2-pic 1b) were evaluated by polarimetry, ultraviolet and circular dichroism spectroscopy. The structure of 1b was determined by single crystal X-ray crystallography and showed a unique terminal monohapto Ti-O disposition of the oximato ligand. All enantiomers have been tested against several cancer cell lines in vitro: prostate PC-3 and DU-145, lung A-549, pancreas MiaPaca-2, colorectal HCT-116, leukemia Jurkat and cervical HeLa. In addition, 1a, 1b and 1b' were tested against non-tumorigenic prostate RWPE-1 cell line. After 24 h of incubation, 1b and 1b' were moderately active against Jurkat and A-549 cells. The anti-proliferative effect of titanium compounds on prostate PC-3, DU-145 and RWPE-1 cell lines was also assessed after 72 h of drug exposure. The cytotoxic profile of the enantiomers was similar, exception made for the PC-3 cells, with S,R-isomers exhibiting cytotoxicities 2 to 3 times higher than R,S-compounds. Under these conditions, derivative 1b showed calculated IC 50 values better than those of Tacke´s Titanocene-Y (bis-[(p-methoxybenzyl)cyclopentadienyl]titanium(IV) dichloride) on both the prostate PC-3 and DU-145 cells. 1a and 1b cytotoxic behaviour shows certain selectiveness, with activities 2-4 times lower on normal prostate RWPE-1 than on cancer PC-3 cells. Furthermore, 1b produces higher cytotoxicity on prostate PC-3, DU-145 and RWPE-1 cells than the additive dose of titanocene dichloride and pro-ligand b•HCl. Additionally, compound-DNA interactions have been investigated by equilibrium dialysis, Fluorescence Resonance Energy Transfer (FRET) melting assays and viscometric titrations, which suggest that these metal complexes and/or their hydrolysis products bind DNA either in the minor groove or externally. Highlights (85 characters) • Synthesis of novel enantiopure titanocene amino-oximato compounds is reported. • The X-ray crystal structure of one of the compounds shows a unique monohapto Ti-ON coordination. • One enantiomer shows IC 50 values lower than Titanocene-Y on both PC-3 and DU-145 cells. • One enantiomer is more active than additive doses of Ti(η 5-C 5 H 5)Cl 2 and oxime pro-ligand.

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“…About more than half of the drugs currently in clinical use are chiral compounds, marketed as racemates or as single enantiomers. The anticancer properties of chiral metal derivatives have been largely explored [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36], but the role of the stereochemistry in the biological activity of non-platinum based compounds has been less investigated [18][19][20][37][38][39][40][41][42][43][44][45][46][47][48].…”

Section: Introductionmentioning

confidence: 99%

Biological evaluation of water soluble arene Ru(II) enantiomers with amino-oxime ligands

Cueva-Alique

Sierra

Muñoz-Moreno

et al. 2018

Journal of Inorganic Biochemistry

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New water soluble, enantiopure arene ruthenium compound SS-(1R,4S)-[(η-p-cymene)Ru{ĸNH(Bn),ĸNOH}Cl]Cl (Bn = benzyl, 1a') has been synthesized. The novel compound along with that previously described RR-(1S,4R)-[(η-p-cymene)Ru{ĸNH(Bn),ĸNOH}Cl]Cl (1a) was evaluated by polarimetry, ultra-violet and circular dichroism spectroscopy. The structure of novel ruthenium derivative 1a' was determined by single crystal X-ray crystallography. Both enantiomers have been tested against several cancer cell lines in vitro: prostate PC-3, lung A-549, pancreas MIA PaCa-2, colorectal HCT-116, leukemia Jurkat and cervical HeLa. Both enantiomers are active and versatile cytotoxic agents, showing IC values from 2 to 12 times lower than those found for cisplatin in the different cell lines evaluated. The mechanism of cell death induced by the metal compounds was analyzed in A-549 and Jurkat cell lines. Derivatives 1a and 1a' induced apoptotic cell death of A-549 cells while dose-dependent cell death mechanisms have been found in the Jurkat cell line. Compound-DNA interactions have been investigated by equilibrium dialysis, Fluorescence Resonance Energy Transfer (FRET) melting assays and viscometric titrations, revealing moderate binding affinity of 1a and 1a' towards duplex DNA. Finally, the efficacy of 1a in a preliminary in vivo assay of PC-3 xenografts in nude mice has been evaluated, resulting in a promising inhibition of tumor growth by 45%. Analysis of tumor tissue also showed a significant decrease of levels of crucial molecules in the invasive phenotype of PC-3 cells.

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A multifunctional molecular entity Cu^II–Sn^IV heterobimetallic complex as a potential cancer chemotherapeutic agent: DNA binding/cleavage, SOD mimetic, topoisomerase Iα inhibitory and in vitro cytotoxic activities

Abstract: New chiral l-valine-derived Schiff base complexes with the bioactive heterocyclic ligand scaffold pyrazole (Hpz) were designed and synthesized with a view to find their potential as anticancer chemotherapeutic drug candidates.

Cited by 34 publications

References 66 publications

Synthesis, characterization and binding studies of novel diorganotin(IV) complexes of sodium 2‐mercaptoethanesulfonate

Synthesis, characterization and binding studies of novel diorganotin(IV) complexes of sodium 2‐mercaptoethanesulfonate

Study of the anticancer properties of optically active titanocene oximato compounds

Biological evaluation of water soluble arene Ru(II) enantiomers with amino-oxime ligands

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A multifunctional molecular entity CuII–SnIV heterobimetallic complex as a potential cancer chemotherapeutic agent: DNA binding/cleavage, SOD mimetic, topoisomerase Iα inhibitory and in vitro cytotoxic activities

Abstract: New chiral l-valine-derived Schiff base complexes with the bioactive heterocyclic ligand scaffold pyrazole (Hpz) were designed and synthesized with a view to find their potential as anticancer chemotherapeutic drug candidates.

Cited by 34 publications

References 66 publications

Synthesis, characterization and binding studies of novel diorganotin(IV) complexes of sodium 2‐mercaptoethanesulfonate

Synthesis, characterization and binding studies of novel diorganotin(IV) complexes of sodium 2‐mercaptoethanesulfonate

Study of the anticancer properties of optically active titanocene oximato compounds

Biological evaluation of water soluble arene Ru(II) enantiomers with amino-oxime ligands

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A multifunctional molecular entity Cu^II–Sn^IV heterobimetallic complex as a potential cancer chemotherapeutic agent: DNA binding/cleavage, SOD mimetic, topoisomerase Iα inhibitory and in vitro cytotoxic activities