School Of Basic And Applied Sciences
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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 Recent advances in decarboxylative C-C bond formation using direct or in situ generated alkenyl acids(Taylor and Francis Inc., 2020) Kaur, P; Kumar, V; Kumar, R.In recent years, the reactions of abundantly available, inexpensive, and structurally diverse alkenyl acids (-C=C-COOH) with C-X (X�=�halogen) or C-H coupling partner have emerged as vital strategies for the streamlined synthesis of functionalized alkenes with extrusion of innocuous CO2. Various alkenyl acids such as cinnamic acids can act as stable surrogates for the polymerization prone styrenes/olefins, which otherwise need special attention for their handling and storage. Furthermore, cinnamic acids can be easily prepared through various methodologies including Knoevenagel-Doebner (KD) condensation, Heck coupling reaction, etc. Recently, various one-pot tandem methodologies involving the decarboxylative coupling of KD/Heck sequence with C-H or C-X substrate have come into fore. The present review article edifies about the recent advances, scope and limitations for C-C bond formation via (i) direct decarboxylative functionalization of C-X or C-H substrate with alkenyl acids, (ii) tandem one-pot multicomponent decarboxylative approaches (involving in situ generated alkenyl acids) e.g. coupling of KD/Heck sequences with C-X or C-H substrate. � 2019, � 2019 Taylor & Francis.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 Recent advances in the C(1)-functionalization of tetrahydroisoquinolines via multicomponent reactions(Springer, 2020) Kaur, P; Kumar, R.(Figure presented.) 1,2,3,4-Tetrahydroisoquinoline is an important structural motif of various natural products and therapeutic lead compounds. In recent years, considerable research interest has been witnessed toward synthesis of its C(1)-substituted derivatives, since they can act as precursors for various alkaloids displaying multifarious biological activities. This minireview offers short and non-exhaustive epitome of various multicomponent reactions for the C(1)-functionalization of 1,2,3,4-tetrahydroisoquinolines. In particular, reactions involving isomerization of iminium intermediate (exo/endo isomerization) are highlighted for the period of 2013-2019. - 2020, Springer Science+Business Media, LLC, part of Springer Nature.Item Cyclocondensation reactions of an electron deactivated 2-aminophenyl tethered imidazole with mono/1, 2-biselectrophiles: synthesis and DFT studies on the rationalisation of imidazo [1, 2-a] quinoxaline versus benzo [f] imidazo [1, 5-a][1, 3, 5] triazepine selectivity switches.(Royal Society of Chemistry, 2018) Joshi, G.; Chauhan, M; Kumar, R; Thakur, A; Sharma, S; Singh, R.; Wani, A.A.; Sharon, A.; Bharatam, P.V; Kumar, R.Microwave-promoted ring-closure reactions of 5-amino-1-(2-aminophenyl)-1H-imidazole-4-carbonitrile (7) with various mono/1,2-biselectrophiles are presented. The reaction of 7 with aldehydes, ketones and isocyanates produced the corresponding Pictet–Spengler (PS) products i.e. the imidazo[1,2-a]quinoxaline ring system via 6-endo-trig cyclisation. On the other hand, the reaction of 7 with CH(OEt)3, and CDI resulted in the formation of benzo[f]imidazo[1,5-a][1,3,5]triazepine scaffolds via a 7-exo-trig cyclisation process. The mechanistic aspects of these ring cyclisation processes have been analysed and studied to rationalise 6- versus 7-membered ring formation using density functional theory (DFT). DFT calculations revealed the involvement of N-Heterocyclic Carbene (NHC) in the PS reaction mechanism.Item Unanticipated Cleavage of 2-Nitrophenyl-Substituted N-Formyl Pyrazolines under Bechamp Conditions: Unveiling the Synthesis of 2-Aryl Quinolines and Their Mechanistic Exploration via DFT Studies.(ACS Publications, 2018) Joshi, G; Wani, A.A.; Sharma, S; Bhutani, P; Bharatam, P.V.; Paul, A.T.; Kumar, R.We herein report for the first time an unusual decomposition of 2-nitrophenyl-substituted N-formyl pyrazolines under Bechamp reduction condition employed to yield 2-aryl quinolines exclusively instead of pyrazolo[1,5-c]quinazolines. The reaction investigation suggests acid-mediated cleavage of 1 followed by a retro-Michael addition, and a subsequent in situ intramolecular reductive cyclization through a modified Friedlander mechanism afforded 2-aryl quinolines (2) in good yields. The proposed mechanistic pathways were supported via experimental evidence and density functional theory studies. B3LYP/6-31+G(d) analysis indicated the involvement of trans-2-hydroxyaminochalcone as a key intermediate and its isomerization and cyclization, leading to unusual product formation.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 Anticancer activity of dihydropyrazolo[1,5-c]quinazolines against rat C6 glioma cells via inhibition of topoisomerase II.(Wiley, 2018) Kaur, G; Cholia, RP; Joshi, G; Amrutkar, SM; Kalra, S; Mantha, Anil K.; Banerjee, UC; 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 modeling.Item 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.