Pharmaceutical Sciences and Natural Products - Research Publications
Permanent URI for this collectionhttps://kr.cup.edu.in/handle/32116/56
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Item Isolation, Characterization, and Quantification of a New Anticancer Constituent from Leaves of Nyctanthes arbor-tristis(Springer, 2022-05-03T00:00:00) Grover, P.; Kaur, J.; Suri, K.A.; Kumar, R.; Bansal, G.A new compound, 1,1,2-tris(2?,4?-di-tert-butylphenyl)-4,4-dimethylpent-1-ene, was isolated and characterized from the leaves of Nyctanthes arbor-tristis L. The plant was subjected to bioactivity-guided fractionation, and a compound was isolated from chloroform extract that was found to have potent anticancer activity. The chloroform extract was further fractionated, and a pure compound was isolated that was found to be active against three cancer cell lines (HL-60, HCT-116, and A-549). An RP-HPLC method was developed for quantification of the isolated compound. The content of the isolated compound was 0.88% in the chloroform extract and 0.08% in N. arbor-tristis leaves. � 2022, Springer Science+Business Media, LLC, part of Springer Nature.Item Epidermal growth factor receptor and its trafficking regulation by acetylation: Implication in resistance and exploring the newer therapeutic avenues in cancer(Bentham Science Publishers, 2020) Kumar, M; Joshi, G; Chatterjee, J; Kumar, R.Background: The EGFR is overexpressed in numerous cancers. So, it becomes one of the most favorable drug targets. Single-acting EGFR inhibitors on prolong use induce resistance and side effects. Inhibition of EGFR and/or its interacting proteins by dual/combined/multitargeted therapies can deliver more efficacious drugs with less or no resistance. Objective: The review delves deeper to cover the aspects of EGFR mediated endocytosis, leading to its trafficking, internalization, and crosstalk(s) with HDACs. Methods and Results: This review is put forth to congregate relevant literature evidenced on EGFR, its impact on cancer prognosis, inhibitors, and its trafficking regulation by acetylation along with the current strategies involved in targeting these proteins (EGFR and HDACs) successfully by involving dual/hybrid/combination chemotherapy. Conclusion: The current information on cross-talk of EGFR and HDACs would likely assist researchers in designing and developing dual or multitargeted inhibitors through combining the required pharmacophores. � 2020 Bentham Science Publishers.Item Anticancer activity of dihydropyrazolo [1, 5‐c] quinazolines against rat C6 glioma cells via inhibition of topoisomerase II(wiley, 2018) Kaur, G; Cholia, Raman Preet; Joshi, G; Amrutkar, S.M; Kalra, S; Mantha, Anil K.; Banerjee, U.C; Kumar, R.The 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 modelingItem Topoisomerase inhibitors: Classification, mechanisms of action and adverse effects(Nova Science Publishers, Inc., 2017) Kumar, R.; Singh, S.This book aims to assist the scientists working with the medicinal, biochemical, biophysical, genetic and pharmacological aspects of topoisomerases and their inhibitors. The book has covered various aspects of topoisomerases like classification, structural aspects, basic genetics and mutations, disease implications and cell signaling networks, which may be helpful for researchers of the field for better therapeutics. Chapter One deals with structure, functions and role and of human topoisomerase-I in cancer progression. It describes a detailed classification, mechanism of action and recent updates on the development of camptothecin and non-camptothecin derivatives, along with their Structure-Activity Relationships (SAR) as topoisomerase-I inhibitors. Chapters Two and Three cover X-ray co-crystal structures, biological functions and the significant role of topoisomerase-II isoforms in cancer. A thorough discussion on classification and various pharmacoinformatics techniques employed in delineating the binding mode of topoisomerase-II inhibitors and their mechanism of action is well presented. Chapter Four deals not only with adverse effects associated with the use of topoisomerase-I and II inhibitors, but also includes approaches to overcome them. Chapter Five discusses various disorders associated with SNPs in topoisomerases and risks associated with their pharmacogenetics. Chapter Six sheds light on interactions and cross-talks between topoisomerases and histone deacetylases, leading to their significant role in drug resistance. The work is expected to assist the scientists to selectively design dual/multi-inhibitors of topoisomerases and histone deacetylases. The authors are thankful to the reviewers, who were so kind in reviewing and making suggestions for improving this book. This book could not have been completed without their commendable efforts. (Imprint: Nova Biomedical). ? 2017 by Nova Science Publishers, Inc. All rights reserved.Item Recent advancements in small molecule inhibitors of insulin-like growth factor-1 receptor (IGF-1R) tyrosine kinase as anticancer agents(2013) Negi, A.; Ramarao, P.; Kumar, R.Advancements in understanding of the genetics, genomics, biochemistry and the pharmacology of cancer in human, have driven the current cancer chemotherapy to intently focus on development of target-based approaches rather than conventional approaches. From among the various targets identified, validated and inhibited at different hallmarks of cancer, protein tyrosine kinases (PTKs) have been exploited the most. Insulin receptors (IRs), insulin like growth factor receptors (IGF-1R) and their hybrid receptors belong to tyrosine kinase receptor (TKR) family, constitute a structural homology among them and generate a growth promoting IGF system on binding with either insulin, IGF-1 or IGF-2. The system induces the mitogenic effects through a torrent of cell signals produced as a result of cross talk with other growth promoting peptides and steroidal hormones, ultimately resulting in hijacking apoptosis and increasing cell proliferation and cell survival in cancer cells. Various strategies such as anti-IGF-1R antibodies, IGF-1 mimetic peptides, antisense strategies, IGF-1R specific peptide aptamers, targeted degradation of IGF-1R and expression of dominant negative IGF-1R mutants have been explored to inhibit the IGF-1R signaling. However, targeting IGF-1R with small molecules has gained considerable attention in last few years due to their ease of synthesis, ease of optimization of absorption, distribution, metabolism, excretion and toxicity (ADMET) parameters, oral route of administration, lesser side effects and cost effectiveness. The present review provides a broad overview and discusses the highlights on discoveries, SAR studies and binding interactions of small molecules with either IGF-1R active or allosteric sites reported till date. ? 2013 Bentham Science Publishers.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.