Pharmaceutical Sciences and Natural Products - Research Publications
Permanent URI for this collectionhttps://kr.cup.edu.in/handle/32116/56
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Item Interaction between topoisomerases and histone deacetylases: Role in cancer progression and therapeutic interventions(Nova Science Publishers, Inc., 2017) Joshi, G.; Thakur, A.; Kaur, G.; Kalra, S.; Singh, S.; Kumar, R.DNA topoisomerases are termed as the magicians of the DNA world, as they are involved in overcoming all the topological DNA problems. Histone Deacetylases are the collection of enzymes that assist in the regulation of DNA control. The overexpression of topoisomerases and histone deacetylases are found in various diseases including cancer. Till date, many therapies have been discovered to target topoisomerases and histone deacetylases individually. However, most of these treatments are associated with the toxicities and drug resistance. The drug resistance apart from known mechanism(s) could occur due to crosstalk(s) of topoisomerases with various proteins associated directly or indirectly with the cancer prognosis. Histone deacetylases that render topoisomerase inhibitors resistant also insensitize them toward binding to the receptor. The chapter overlays the discussion on the underlying mechanism(s) involved in topoisomerase and histone deacetylases interactions. The chapter also congregates the information suggested for the essential pharmacophore development for such hybrid drug discovery. The attempt has also been made to give a preliminary virtual background on the fundamental interaction of these two proteins along with the primary amino acids involved in such interaction. ? 2017 Nova Science Publishers, Inc.Item Anticancer activity of dihydropyrazolo[1,5-c]quinazolines against rat C6 glioma cells via inhibition of topoisomerase II(Wiley-VCH Verlag, 2018) Kaur, G.; Cholia, R.P.; Joshi, G.; Amrutkar, S.M.; Kalra, S.; Mantha, Anil K.; Banerjee, U.C.; Kumar, RajThe design and synthesis of dihydropyrazolo[1,5-c]quinazolines (1a?h) as human topoisomerase II (TopoII) catalytic inhibitors are reported. The compounds were investigated for their antiproliferative activity against the C6 rat glial cell line. Two compounds, 1b and 1h, were found to be potent cytotoxic agents against glioma cells and exerted selective TopoII inhibitory activity. Furthermore, the compounds induced alterations in reactive oxygen species levels as measured by DCFDA assay and were found to induce cell cycle arrest at the G1 phase at lower concentrations and profound apoptosis at higher concentrations. The interaction of selected investigational molecules with TopoII was further corroborated by molecular modeling. ? 2018 Deutsche Pharmazeutische Gesellschaft