Copper conjugates of nimesulide Schiff bases targeting VEGF, COX and Bcl-2 in pancreatic cancer cells

Ambike, Vinita; Adsule, Shreelekha; Ahmed, Fakhara; Wang, Zhiwei; Afrasiabi, Zahra; Sinn, Ekkehard; Sarkar, Fazlul H.; Padhyé, Subhash

doi:10.1016/j.jinorgbio.2007.06.028

Cited by 67 publications

(23 citation statements)

References 30 publications

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“…181 Copper conjugates showed significantly higher growth inhibition in both cell lines (IC 50 values 3-26 mM for COX-2 positive and 5-9 mM for COX-2 negative cell line) than uncoordinated nimesulide (35 mM for COX-2 positive and 4100 mM for COX-2 negative cell line). 181 The authors reported that the mechanistic pathway responsible for the biological activity involved the inhibition of VEGF and COX-2, as well as the down regulation of antiapoptotic Bcl-2 and Bcl-XL proteins. 181 By using a similar approach, Padhye et al 182 have shown that the central ketonic function of another NSAID, ketoprofen, could be appended onto TSCs bearing amino groups to yield Schiff base type compounds.…”

Section: Copper Complexes With Tscs and Schiff-base Ligandsmentioning

confidence: 92%

“…181 Copper conjugates of Schiff base derivatives of nimesulide were synthesized, structurally characterized (see compound (3a) in Scheme 3) and evaluated for their COX selectivity indices and cytotoxicities in pancreatic tumor BxPC-3 (COX-2 positive) and MiaPaCa (COX-2 negative) cell lines. 181 Copper conjugates showed significantly higher growth inhibition in both cell lines (IC 50 values 3-26 mM for COX-2 positive and 5-9 mM for COX-2 negative cell line) than uncoordinated nimesulide (35 mM for COX-2 positive and 4100 mM for COX-2 negative cell line). 181 The authors reported that the mechanistic pathway responsible for the biological activity involved the inhibition of VEGF and COX-2, as well as the down regulation of antiapoptotic Bcl-2 and Bcl-XL proteins.…”

Section: Copper Complexes With Tscs and Schiff-base Ligandsmentioning

confidence: 99%

“…181 The authors reported that the mechanistic pathway responsible for the biological activity involved the inhibition of VEGF and COX-2, as well as the down regulation of antiapoptotic Bcl-2 and Bcl-XL proteins. 181 By using a similar approach, Padhye et al 182 have shown that the central ketonic function of another NSAID, ketoprofen, could be appended onto TSCs bearing amino groups to yield Schiff base type compounds. Reaction of these ligands with copper yielded several compounds, among which (3b) exhibited a potent antiproliferative and proapoptotic activity in COX-2 positive cells.…”

Section: Copper Complexes With Tscs and Schiff-base Ligandsmentioning

confidence: 99%

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Copper in diseases and treatments, and copper‐based anticancer strategies

Tisato¹,

Marzano

Porchia³

et al. 2009

Medicinal Research Reviews

671

420

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Copper is found in all living organisms and is a crucial trace element in redox chemistry, growth and development. It is important for the function of several enzymes and proteins involved in energy metabolism, respiration, and DNA synthesis, notably cytochrome oxidase, superoxide dismutase, ascorbate oxidase, and tyrosinase. The major functions of copper-biological molecules involve oxidation-reduction reactions in which they react directly with molecular oxygen to produce free radicals. Therefore, copper requires tightly regulated homeostatic mechanisms to ensure adequate supplies without any toxic effects. Overload or deficiency of copper is associated, respectively, with Wilson disease (WD) and Menkes disease (MD), which are of genetic origin. Researches on Menkes and Wilson disorders have provided useful insights in the field of copper homeostasis and in particular into the understanding of intracellular trafficking and distribution of copper at molecular levels. Therapies based on metal supplementation with copper histidine or removal of copper excess by means of specific copper chelators are currently effective in treating MD and WD, respectively. Copper chelation therapy is now attracting much attention for the investigation and treatment of various neurodegenerative disorders such as Alzheimer, Parkinson and CreutzfeldtJakob. An excess of copper appears to be an essential co-factor for angiogenesis. Moreover, elevated levels of copper have been found in many types of human cancers, including prostate, breast, colon, lung, and brain. On these basis, the employment of copper chelators has been reported to be of therapeutic value in the treatment of several types of cancers as anti-angiogenic molecules. More recently, mixtures of copper chelators with copper salts have been found to act as efficient proteasome inhibitors and apoptosis inducers, specifically in cancer cells. Moreover, following the worldwide success of platinum(II) compounds in cancer chemotherapy, several families of individual copper complexes have been studied as potential antitumor agents. These investigations, revealing the occurrence of mechanisms of action quite different from platinum drugs, head toward the development of new anticancer metallodrugs with improved specificity and decreased toxic side effects.

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Section: Copper Complexes With Tscs and Schiff-base Ligandsmentioning

confidence: 92%

Section: Copper Complexes With Tscs and Schiff-base Ligandsmentioning

confidence: 99%

Section: Copper Complexes With Tscs and Schiff-base Ligandsmentioning

confidence: 99%

See 1 more Smart Citation

Copper in diseases and treatments, and copper‐based anticancer strategies

Tisato¹,

Marzano

Porchia³

et al. 2009

Medicinal Research Reviews

671

420

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show abstract

“…Similarly, azomethine moiety has gained a great importance, since it has been found to possess several biological activities, such as antimicrobial [44][45][46][47], antiviral [48,49], antioxidant [50], radical inhibitor [51], antitumor [52,53], carbonic anhydrase inhibitor [54], xanthine oxidase inhibitor [55], antibacterial [56][57][58][59], plant growth regulator [60], free radical scavenger [61], trypsin inhibitor [62], inhibitor of cartilage matrix degeneration [63], 5-HT6 antagonist [64], anti-inflammatory [65] and analgesic [66,67]. Similarly, chalcones (α,β-unsatured ketones) captivated significant attention in drug discovery chemistry.…”

Section: Methodsmentioning

confidence: 99%

Synthesis, characterization and in vitro biological evaluation of some new 1,3,5-triazine-chalcone hybrid molecules as Mycobacterium tuberculosis H37Rv inhibitors

et al. 2014

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“…In more recent years there have been numerous reports highlighting the significant biological activity of Cu(II) Schiff base complexes [40][41][42][43][44][45][46]. Patil et al detailed the preparation of Co(II), Ni(II) and Cu(II) complexes with 1,2,4-triazole-derived coumarin Schiff bases and assessed their biological activity [47].…”

Section: Introductionmentioning

confidence: 99%