Topoisomerase as target for antibacterial and anticancer drug discovery

Kathiravan, Muthu K.; Khilare, Madhavi; Nikoomanesh, Kiana; Chothe, Aparna S.; Jain, Kishor S.

doi:10.3109/14756366.2012.658785

Cited by 84 publications

(43 citation statements)

References 95 publications

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“…In the recent past, there has been a surge in biochemical and biological aspects of topoII and various processes underlying its functions and reactions have been established (Nitiss, 2009; Blattner, 2016) but studies are mostly restricted to animal system. TopoII has been extensively studies in animals not only with reference to change in DNA topology but with respect to a large number of topoisomerase-targeted drugs that have been identified possessing antimicrobial and anticancerous activities (Kathiravan et al, 2013; Ashour et al, 2014). Most of these drugs interfer with the processing of the DNA break, causing stabilization of transient covalent DNA–DNA topoisomerase complex into a form that is harmful for the cell (Gadelle et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Over-expression of Topoisomerase II Enhances Salt Stress Tolerance in Tobacco

et al. 2016

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Topoisomerases are unique enzymes having an ability to remove or add DNA supercoils and untangle the snarled DNA. They can cut, shuffle, and religate DNA strands and remove the torsional stress during DNA replication, transcription or recombination events. In the present study, we over-expressed topoisomerase II (TopoII) in tobacco (Nicotiana tabaccum) and examined its role in growth and development as well as salt (NaCl) stress tolerance. Several putative transgenic plants were generated and the transgene integration and expression was confirmed by PCR and Southern blot analyses, and RT-PCR analysis respectively. Percent seed germination, shoot growth, and chlorophyll content revealed that transgenic lines over-expressing the NtTopoIIα-1 gene exhibited enhanced tolerance to salt (150 and 200 mM NaCl) stress. Moreover, over-expression of TopoII lead to the elevation in proline and glycine betaine levels in response to both concentrations of NaCl as compared to wild-type. In response to NaCl stress, TopoII over-expressing lines showed reduced lipid peroxidation derived malondialdehyde (MDA) generation. These results suggest that TopoII plays a pivotal role in salt stress tolerance in plants.

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Section: Introductionmentioning

confidence: 99%

Over-expression of Topoisomerase II Enhances Salt Stress Tolerance in Tobacco

et al. 2016

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“…Fluoroquinolones (FQs) have been identified for over 40 years as one of the most clinically successful antibacterials (Appelbaum et al, 2000;Ball, 2000;Langer et al, 2003;Bolon 2011). FQs have other biological activities as antidiabetic (Edmont et al, 2000), antimycobacterial, pancreatic lipase inhibitors as well as anticancer properities (El-Rayes et al, 2002;Zhao et al, 2005;Shaharyar et al, 2007;Kathiravan et al, 2013; receptors (RAGEs) on the cell surface induces the overproduction of reactive oxygen species (ROSs) and inflammatory mediators, which leads to cellular disorders in biological systems (Wu et al, 2011a;Wu et al, 2011b). Recently, more detrimental effects of AGEs in type 2 DM have emerged.…”

Section: Introductionmentioning

confidence: 99%

Dual Glycation-Inflammation Modulation, DPP-IV and Pancraetic Lipase Inhibitory Potentials and Antiproliferative Activity of Novel Fluoroquinolones

Arabiyat

Kasabri

Al‐Hiari

et al. 2019

Asian Pac J Cancer Prev

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Paramount efforts by pharmaceutical industry to identify new targets for obesity-diabetes (Diabesity) pharmacological intervention have led to a number of agents developed and directed at DPP IV [dipeptidyl peptidase IV] enzyme inhibition thereby enhancing endogenous insulinotropic incretins. Besides antioxidative-antiinflammtory molecules that inhibit accumulation of advanced glycation end products (AGEs) can be good candidates for ameliorating diabetic complications. Fluoroquinolones (FQs) have been identified recently as potent inhibitors of pancreatic lipase (PL). The suggested association between obesity and colorectal cancer initiated the evaluation of antiproliferative activity of the new FQs and TFQs against a panel of obesity related colorectal cells (HT29, HCT116, SW620 CACO2 and SW480). The aim of the current study is to examine the potential of newly synthesized FQs and triazolofluoroquinolones (TFQs) derivatives as dual inhibitors for glycation and inflammation, DPP IV inhibitors, PL inhibitors for dual management of obesity and diabetes, as well as antiprolifertaive efficacy against colorectal cancer cell lines. Sulforodamine B (SRB) colorimetric assay revealed that some derivatives exhibited unselective cytotoxity against HT29, HCT116, SW620 CACO2 and SW480. The superior antiglycation activity of the reduced derivatives 4a and 4b over that of aminoguanidine with respective IC50 (µM) values of 3.05±0.33 and 8.51±3.21; none of the tested synthetic compounds could perform equally effectively to Diprotin A, a dose dependent inhibitor of DPP IV. Compounds 4a, 5a, 3b, 4b and 5b demonstrated anti-inflammatory IC50 values exceeding that of indomethacin. Compounds 3a and 4a showed IC50 lower than 10 μM as PL inhibitors. In conclusion, FQ and TFQ derivatives may unveil new antiobesity and anticancer agents in the future. Our research qualifies FQs and TFQs as promising candidates for the development of related α-dicarbonyl scavengers as therapeutic agents to protect cells against carbonyl stress.

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“…By transiently breaking and resealing the DNA backbone via a transesterification reaction (Champoux 2001; Chen et al 2013; Forterre et al 2007; Schoeffler and Berger 2008), topoisomerases can modulate the level of supercoiling and maintain the topological homeostasis of genomic DNA (Nitiss 2009a; Vos et al 2011; Wang 2002). Given the fundamental roles of topoisomerases in nucleic acid metabolism, and their importance as potent targets for anti-bacterial and anti-cancer agents, they have been, and continue to be, extensively studied (Deweese and Osheroff 2009; Kathiravan et al 2013; Nitiss 2009b; Pommier 2013). …”

Section: Introductionmentioning

confidence: 99%

The dynamic interplay between DNA topoisomerases and DNA topology

Seol

Neuman

2016

Biophys Rev

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Topological properties of DNA influence its structure and biochemical interactions. Within the cell DNA topology is constantly in flux. Transcription and other essential processes including DNA replication and repair, alter the topology of the genome, while introducing additional complications associated with DNA knotting and catenation. These topological perturbations are counteracted by the action of topoisomerases, a specialized class of highly conserved and essential enzymes that actively regulate the topological state of the genome. This dynamic interplay among DNA topology, DNA processing enzymes, and DNA topoisomerases, is a pervasive factor that influences DNA metabolism in vivo. Building on the extensive structural and biochemical characterization over the past four decades that established the fundamental mechanistic basis of topoisomerase activity, the unique roles played by DNA topology in modulating and influencing the activity of topoisomerases have begun to be explored. In this review we survey established and emerging DNA topology dependent protein-DNA interactions with a focus on in vitro measurements of the dynamic interplay between DNA topology and topoisomerase activity.

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Topoisomerase as target for antibacterial and anticancer drug discovery

Cited by 84 publications

References 95 publications

Over-expression of Topoisomerase II Enhances Salt Stress Tolerance in Tobacco

Over-expression of Topoisomerase II Enhances Salt Stress Tolerance in Tobacco

Dual Glycation-Inflammation Modulation, DPP-IV and Pancraetic Lipase Inhibitory Potentials and Antiproliferative Activity of Novel Fluoroquinolones

The dynamic interplay between DNA topoisomerases and DNA topology

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