Mechanistic studies of <i>in vitro</i> anti-proliferative and anti-inflammatory activities of the Zn(<scp>ii</scp>)–NSAID complexes of 1,10-phenanthroline-5,6-dione in MDA-MB-231 cells

Deb, Jolly; Lakshman, Triloke Ranjan; Ghosh, Ivy; Jana, Siddhartha S.; Paine, Tapan Kanti

doi:10.1039/d0dt01721c

Cited by 32 publications

(25 citation statements)

References 68 publications

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“…According to literature, among the available NSAIDs−metal ion complexes, Cu(II)−NSAID complexes have the best anticancer effects, probably due to their well-known ability to reduce inflammatory processes [ 115 , 116 ]. Nevertheless, Deb and co-workers synthetized and characterized a Zn(II)–naproxen complex and a Zn(II)–mefenamate complex, which proved to have cytotoxic cell killing properties against a breast cancer cell line (MDA-MB-231) [ 117 ]. Of note, other metal-based compounds (besides the ones covered by this review) with anti-tumor potential, such as platinum−indomethacin and platinum−tolmetin complexes, have been proved to inhibit the growth of the L929 cancer cell line [ 118 ].…”

Section: Biological Effects Of the Metal Complexesmentioning

confidence: 99%

NSAID-Based Coordination Compounds for Biomedical Applications: Recent Advances and Developments

Santos

Monteiro

Gomes

et al. 2022

IJMS

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After the serendipitous discovery of cisplatin, a platinum-based drug with chemotherapeutic effects, an incredible amount of research in the area of coordination chemistry has been produced. Other transition metal compounds were studied, and several new relevant metallodrugs have been synthetized in the past few years. This review is focused on coordination compounds with first-row transition metals, namely, copper, cobalt, nickel or manganese, or with zinc, which have potential or effective pharmacological properties. It is known that metal complexes, once bound to organic drugs, can enhance the drugs’ biological activities, such as anticancer, antimicrobial or anti-inflammatory ones. NSAIDs are a class of compounds with anti-inflammatory properties used to treat pain or fever. NSAIDs’ properties can be strongly improved when included in complexes using their compositional N and O donor atoms, which facilitate their coordination to metal ions. This review focuses on the research on this topic and on the promising or effective results that complexes of first-row transition metals and NSAIDs can exhibit.

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Section: Biological Effects Of the Metal Complexesmentioning

confidence: 99%

NSAID-Based Coordination Compounds for Biomedical Applications: Recent Advances and Developments

Santos

Monteiro

Gomes

et al. 2022

IJMS

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“…In vitro cell migration and EMT‐related genes (VIMENTIN and β1‐INTEGRIN) also decrease. Mechanistic studies indicate that ternary complexes are more active than cisplatin and can overcome cisplatin resistance in MDA‐MB‐231 cells [82].…”

Section: Metallodrugs Against Migration and Metastatic Processesmentioning

confidence: 99%

“…Recently, Deb et al (2020) [82] reported the synthesis, characterization, and biological evaluation of a zinc(II)-naproxen and a zinc(II)-mefenamic acid complex of 1,10-phenanthroline-5,6-dione [82]. Both complexes exhibit antiproliferative activity in the human breast cancer cell line MDA-MB-231.…”

Section: Proposed Mechanisms Of Actionmentioning

confidence: 99%

Metallodrugs: an approach against invasion and metastasis in cancer treatment

2022

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Cancer is a heterogeneous and multifactorial disease that causes high mortality throughout the world; therefore, finding the most effective therapies is a major research challenge. Currently, most anticancer drugs present a limited number of well‐established targets, such as cell proliferation or death; however, it is important to consider that the worse progression of cancer toward pathological stages implies invasion and metastasis processes. Medicinal Inorganic Chemistry (MIC) is a young area that deals with the design, synthesis, characterization, preclinical evaluation, and mechanism of action of new inorganic compounds, called metallodrugs. The properties of metallic ions allow enriching of strategies for the design of new drugs, enabling the adjustment of physicochemical and stereochemical properties. Metallodrugs can adopt geometries, such as tetrahedral, octahedral, square planar, and square planar pyramid, which adjusts their arrangement and facilitates binding with a wide variety of targets. The redox properties of some metal ions can be modulated by the presence of the bound ligands to adjust their interaction, thereby opening a range of mechanisms of action. In this regard, the mechanisms of action that trigger the biological activity of metallodrugs have been generally identified by: (a) coordination of the metal to biomolecules (for instance, cisplatin binds to the N7 in DNA guanine, as Pt‐N via coordination of the inhibition of enzymes); (b) redox‐active; and (c) ROS production. For this reason, a series of metallodrugs can interact with several specific targets in the anti‐invasive processes of cancer and can prevent metastasis. The structural base of several metal compounds shows great anticancer potential by inhibiting the signaling pathways related to cancer progression. In this minireview, we present the advances in the field of antimetastatic effects of metallodrugs.

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“…Non-selective COX inhibitors, tolfenamic acid and indomethacin, substantially blocked both TNT formations and the spread of HCMV viruses between fibroblasts [ 115 ]. Recently, the anti-inflammatory and the TNT- and COX-1-inhibitory properties of NSAIDs have been confirmed by using (phendione)ZnII(NPR) 2 (H 2 O) 2 and (phendione)ZnII(MFN) 2 compounds on human breast cancer cell lines [ 116 ]. Although HuR inhibitors are currently available for preclinical evaluations, the combinations of the NSAIDs and gene-specific targeting approaches remain valuable as suppressors of cell fusion and tunneling nanotube formation.…”

Section: Potential Pharmacological Modulators Of Cell Fusionmentioning

confidence: 99%

ELAVL1 Role in Cell Fusion and Tunneling Membrane Nanotube Formations with Implication to Treat Glioma Heterogeneity

Filippova

Nabors

2020

Cancers

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Homotypic and heterotypic cell fusions via permanent membrane fusions and temporal tunneling nanotube formations in the glioma microenvironment were recently documented in vitro and in vivo and mediate glioma survival, plasticity, and recurrence. Chronic inflammation, a hypoxic environment, aberrant mitochondrial function, and ER stress due to unfolded protein accumulation upregulate cell fusion events, which leads to tumor heterogeneity and represents an adaptive mechanism to promote tumor cell survival and plasticity in cytotoxic, nutrient-deprived, mechanically stressed, and inflammatory microenvironments. Cell fusion is a multistep process, which consists of the activation of the cellular stress response, autophagy formation, rearrangement of cytoskeletal architecture in the areas of cell-to-cell contacts, and the expression of proinflammatory cytokines and fusogenic proteins. The mRNA-binding protein of ELAV-family HuR is a critical node, which orchestrates the stress response, autophagy formation, cytoskeletal architecture, and the expression of proinflammatory cytokines and fusogenic proteins. HuR is overexpressed in gliomas and is associated with poor prognosis and treatment resistance. Our review provides a link between the HuR role in the regulation of cell fusion and tunneling nanotube formations in the glioma microenvironment and the potential suppression of these processes by different classes of HuR inhibitors.

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Mechanistic studies of in vitro anti-proliferative and anti-inflammatory activities of the Zn(ii)–NSAID complexes of 1,10-phenanthroline-5,6-dione in MDA-MB-231 cells

Abstract: Two zinc(II)-NSAID complexes [(phendione)ZnII(NPR)2(H2O)2] (1) and [(phendione)ZnII(MFN)2] (2) (HNPR = naproxen and HMFN = mefenamic acid) of 1,10-phenanthroline-5,6-dione (phendione) were isolated and characterized to evaluate their potential as anti-cancer agents....

Cited by 32 publications

References 68 publications

NSAID-Based Coordination Compounds for Biomedical Applications: Recent Advances and Developments

NSAID-Based Coordination Compounds for Biomedical Applications: Recent Advances and Developments

Metallodrugs: an approach against invasion and metastasis in cancer treatment

ELAVL1 Role in Cell Fusion and Tunneling Membrane Nanotube Formations with Implication to Treat Glioma Heterogeneity

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