Cationic Ru(II), Rh(III) and Ir(III) complexes containing cyclic -perimeter and 2-aminophenyl benzimidazole ligands: Synthesis, molecular structure, DNA and protein binding, cytotoxicity and anticancer activity

Kumar, Amit; Kumar, Ashish; Gupta, Rakesh; Paitandi, Rajendra Prasad; Singh, Krishna B.; Trigun, Surendra Kumar; Hundal, Maninder Singh; Pandey, Daya Shankar

doi:10.1016/j.jorganchem.2015.10.008

Cited by 60 publications

(22 citation statements)

References 99 publications

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“…The early Acanthamoeba apoptosis observed with the acyclic Sm complex exposure is thought to result from the acyclic structure of EO5 with two terminal alcohol (OH) groups, facilitating interactions with profilin, a membrane protein that has important role in the growth of cytoskeleton, as later shown in detail with a molecular docking simulation. Studies have indeed reported apoptosis trigger by metals with acyclic ligand (Mukherjee et al 2011), while cyclic compounds could initiate necrotic type of cell death (Kumar et al 2016). In agreement, the cyclic Sm complex herein appears to disrupt the Acanthamoeba membrane and release of cellular materials, a trademark of necrosis.…”

Section: Morphological Changes and Modes Of Cell Death Of The Sm Compsupporting

confidence: 66%

Anti-amoebic activity of acyclic and cyclic-samarium complexes on Acanthamoeba

et al. 2018

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This work investigated the anti-amoebic activity of two samarium (Sm) complexes, the acyclic complex [bis(picrato)(pentaethylene glycol)samarium(III)] picrate-referred to as [Sm(Pic)(EO5)](Pic)-and the cyclic complex [bis(picrato)(18-crown-6)samarium(III)] picrate-referred to as [Sm(Pic)(18C6)](Pic). Both Sm complexes caused morphological transformation of the protozoa Acanthamoeba from its native trophozoite form carrying a spine-like structure called acanthopodia, to round-shaped cells with loss of the acanthopodia structure, a trademark response to environmental stress. Further investigation, however, revealed that the two forms of the Sm complexes exerted unique cytotoxicity characteristics. Firstly, the IC of the acyclic complex (0.7 μg/mL) was ~ 10-fold lower than IC of the cyclic Sm complex (6.5 μg/mL). Secondly, treatment of the Acanthamoeba with the acyclic complex caused apoptosis of the treated cells, while the treatment with the cyclic complex caused necrosis evident by the leakage of the cell membrane. Both treatments induced DNA damage in Acanthamoeba. Finally, a molecular docking simulation revealed the potential capability of the acyclic complex to form hydrogen bonds with profilin-a membrane protein present in eukaryotes, including Acanthamoeba, that plays important roles in the formation and degradation of actin cytoskeleton. Not found for the cyclic complex, such potential interactions could be the underlying reason, at least in part, for the much higher cytotoxicity of the acyclic complex and also possibly, for the observed differences in the cytotoxicity traits. Nonetheless, with IC values of < 10 μg/mL, both the acyclic and cyclic Sm complexes feature a promising potential as cytotoxic agents to fight amoebic infections.

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Section: Morphological Changes and Modes Of Cell Death Of The Sm Compsupporting

confidence: 66%

Anti-amoebic activity of acyclic and cyclic-samarium complexes on Acanthamoeba

et al. 2018

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“…Heterocyclic nitrogen-containing ligands are interesting compounds in themselves due both to their structural diversity and variety of pharmaceutical applications. Benzimidazole-containing compounds are a class of these compounds that often exhibit anti-inflammatory, antifungal, antibacterial, antioxidant, and antitumor activity [ 23 , 24 ]. These compounds also readily coordinate to metal ions, and their structure, flexibility, and bulkiness can all affect the cytotoxic properties of the resulting complexes [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

“…These compounds also readily coordinate to metal ions, and their structure, flexibility, and bulkiness can all affect the cytotoxic properties of the resulting complexes [ 25 ]. Consequently, a variety of different transition-metal complexes with benzimidazole ligands have been reported in medicinal applications [ 24 , 26 , 27 ]. For example, Ru(II), Rh(III), and Ir(III) complexes of 2-aminophenyl benzimidazole have strong binding affinities for both DNA and proteins and show promising cytotoxicity and in vitro anticancer activity against the SiHa human cervical cancer cell line [ 24 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

“…Consequently, a variety of different transition-metal complexes with benzimidazole ligands have been reported in medicinal applications [ 24 , 26 , 27 ]. For example, Ru(II), Rh(III), and Ir(III) complexes of 2-aminophenyl benzimidazole have strong binding affinities for both DNA and proteins and show promising cytotoxicity and in vitro anticancer activity against the SiHa human cervical cancer cell line [ 24 , 28 ]. Similarly, coordination of 2-aminoethyl benzimidazole to Ru(III) was reported to give a complex with in vitro and in vivo cytotoxic activity against human breast MCF7 and colon HCT116 cell lines [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

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Ruthenium(II)/(III) DMSO-Based Complexes of 2-Aminophenyl Benzimidazole with In Vitro and In Vivo Anticancer Activity

et al. 2020

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New anticancer ruthenium(II/III) complexes [RuCl2(DMSO)2(Hapbim)] (1) and [RuCl3(DMSO) (Hapbim)] (2) (Hapbim = 2-aminophenyl benzimidazole) have been synthesized and characterized, and their chemotherapeutic potential evaluated. The interaction of the compounds with DNA was studied by both UV-Visible and fluorescence spectroscopies, revealing intercalation of both the Hapbim ligand and the Ru complexes. The in vitro cytotoxicity of the compounds was tested on human breast cancer (MCF7), human colorectal cancer (Caco2), and normal human liver cell lines (THLE-2), with compound (2) the most potent against cancer cells. The cytotoxic effect of (2) is shown to correlate with the ability of the Ru(III) complex to induce apoptosis and to cause cell-cycle arrest in the G2/M phase. Notably, both compounds were inactive in the noncancerous cell line. The anticancer effect of (2) has also been studied in an EAC (Ehrlich Ascites Carcinoma) mouse model. Significantly, the activity of the complex was more pronounced in vivo, with removal of the cancer burden at doses that resulted in only low levels of hepatotoxicity and nephrotoxicity. An apoptosis mechanism was determined by the observation of increased Bax and caspase 3 and decreased Bcl2 expression. Furthermore, (2) decreased oxidative stress and increased the levels of antioxidant enzymes, especially SOD, suggesting the enhancement of normal cell repair. Overall, compound (2) shows great potential as a chemotherapeutic candidate, with promising activity and low levels of side effects.

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“…Hence, the development of a new generation of transition metal complexes with reduced negative side effects are an important topic. [2][3][4] Copper is an essential trace element that plays an important role in many crucial biological mechanisms and is less toxic for the human body than exogenous metals. 5 It is one of the metals most widely used as chemical nucleases, as it can undergo redox reactions to produce reactive oxygen species (ROS), which are able to split nucleic acid chains.…”

Section: Introductionmentioning

confidence: 99%

Chemical and photo-induced nuclease activity of a novel minor groove DNA binder Cu(II) complex

Yıldız

Çoban

2019

JSCS

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A new type of copper(II) metal complex containing 1,10-phenanthroline (phen) and 8-(difluoromethoxy)-3,4-dihydro-2H-[1,3]thiazino[3,2-a]benzimidazole (dtb) ligands was prepared and characterized. The ds-DNA interaction of the complex was studied by UV-Vis spectrophotometry, competitive fluorometric titration with ethidium bromide (EB) and 4′,6-diamidino-2-phenylindole (DAPI), viscosity measurements and agarose gel electrophoresis. The results show that the complex can bind to ds-DNA in the minor groove by displacing DAPI molecules. DNA cleavage mechanism studies revealed that hydrogen peroxide radicals are responsible for DNA oxidative cleavage.

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Cationic Ru(II), Rh(III) and Ir(III) complexes containing cyclic -perimeter and 2-aminophenyl benzimidazole ligands: Synthesis, molecular structure, DNA and protein binding, cytotoxicity and anticancer activity

Cited by 60 publications

References 99 publications

Anti-amoebic activity of acyclic and cyclic-samarium complexes on Acanthamoeba

Anti-amoebic activity of acyclic and cyclic-samarium complexes on Acanthamoeba

Ruthenium(II)/(III) DMSO-Based Complexes of 2-Aminophenyl Benzimidazole with In Vitro and In Vivo Anticancer Activity

Chemical and photo-induced nuclease activity of a novel minor groove DNA binder Cu(II) complex

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