Pharmaceutical Sciences and Natural Products - Research Publications

Permanent URI for this collectionhttps://kr.cup.edu.in/handle/32116/56

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Subject: search.filters.subject.DNA topoisomerase

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    A comprehensive review on bioactive fused heterocycles as purine-utilizing enzymes inhibitors
    (Birkhauser Boston, 2015) Chauhan, Monika; Kumar, Raj
    Purine-utilizing enzymes (PUEs) are involved in the control of biological actions of nitrogen-containing bases, purines and pyrimidines, by participating in their catabolism, and this has made them a topic of considerate interest. The heterocyclics, as purine-utilizing enzyme inhibitors (PUEIs), play a vital role in a number of diseases, e.g., malaria, cancer, rheumatoid arthritis, inflammation, tissue rejection, and autoimmune disorders. The present review is first of its kind covering the literature up to 2014 on the advances in broad-spectrum medicinal activities exhibited by heterocycles as PUEIs. The drug designing of the purine and pyrimidine antimetabolites is based on the structural mimicking of the existing compounds. The basic consideration during the designing of this class is the introduction of small structural changes without the alteration of basic skeleton of pharmacophore. The balance between the existing empirical approach and rational approach is yet to be maintained during the design and synthesis of new PUEIs by combining in vivo, in vitro, and in silico methods. The data compiled in the present manuscript on SARs, IC50s, Kis, Km, in silico studies, and their reported X-ray co-crystal structures with PUEs will offer the researchers the rational approaches for the design and development of selective and specific PUEIs devoid of adverse effects. ? 2014 Springer Science+Business Media.
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    Epidermal Growth Factor Receptor (EGFR) and its Cross-Talks with Topoisomerases: Challenges and Opportunities for Multi-Target Anticancer Drugs
    (Bentham Science Publishers B.V., 2016) Chauhan, Monika; Sharma, Gourav; Joshi, Gaurav; Kumar, Raj
    Background: The interactions of Epidermal Growth Factor Receptor (EGFR) and topoisomerases have been seen in various cancer including brain, breast, ovarian, colorectal, gastric, etc. Methods: The studies in adenocarcinoma patients, chromogenic in situ hybridization, western blotting, receptor binding assay and electromobility shift assays, etc. threw light on the biophysical and biochemical features of EGFR and Topoisomerase cross-talks. Results: It has been revealed that both the isomers of topoisomerase (Topo I and Topo II) interact via different mechanisms with EGFR. Topo II and HER2 share the same location i.e. 17q12-21 regions which could be a possible cause of predominant interactions seen between them. Topo I and EGFR interactions are mechanically related to the nucleolar translocation of heparenase by EGF and c-Jun. Conclusion: We compiled literature findings including the mechanistic interventions, signaling pathways, patents, in vitro and in vivo data of tested inhibitors and combinations in clinical trials, which provide convincing confirmations for the interactions of EGFR and topoisomerases. These interactions may be used for deriving a consistent route of mechanism, design and development of standard drug combinations and dual or multi inhibitors. ? 2016 Bentham Science Publishers.