School Of Basic And Applied Sciences
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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, 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 Effects of lyotropic anions on thermodynamic stability and dynamics of horse cytochrome c(Elsevier B.V., 2018) Jain, R.; Agarwal, M.C.; Kumar, R.; Sharma, D.; Kumar, R.This paper evaluates the effect of various lyotropic anions (chloride, sulfate, perchlorate, iodide, nitrate, bromide) on the thermodynamic stability and dynamics of native cytochrome c (Cyt c) at pH 7.0. The results of equilibrium and kinetic studies revealed that: (i) at low to intermediate concentrations (? 0.5 M), both chaotropic and kosmotropic anions restrict the dynamics of native protein, (ii) at relatively higher concentrations (? 1.0 M), the denaturing effect of chaotropic anions dominates, which increases the level of structural-fluctuations responsible to unfold the protein according to Hofmeister series (perchlorate > iodide > nitrate > bromide), and (iii) the lyotropic anions affect the thermal and global stability of Cyt c according to Hofmeister series. The m-value was determined from ??G vs [Cosolute] plot and was found to be positive for sulfate and negative for other anions consistent with effect of lyotopic anions on protein stability according to Hofmeister series. ? 2018Item Understanding the multifaceted role of ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) and its altered behaviour in human diseases(Bentham Science Publishers B.V., 2015) Cholia, R.P.; Nayyar, H.; Kumar, R.; Mantha, Anil K.Ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) also known as Autotaxin, is a secreted lysophospholipase D, which hydrolyzes lysophosphatidylcholine (LPC) into Lysophosphatidic acid (LPA). LPA is the bioactive product of ENPP2 enzyme, which induces diverse signalling pathways via six LPA-G-protein coupled receptors (GPCRs). ENPP2 is an essential protein for normal development and its altered expression is associated with various human diseases. Cellular ENPP2 silencing results in lethality at the embryonic stage in mice. Initially, it is identified as an autocrine factor in melanoma cells. Different research groups are currently exploring to understand the multifaceted role of ENPP2 in various processes such as embryonic and neural development, migration, invasion, differentiation, proliferation, angiogenesis, and survival. Altered expression of ENPP2 is also associated with various diseases like inflammation, cancer, fibrosis, rheumatoid arthritis and neural defects. In this article, we have summarized structural aspects of ENPP2 and biochemical functions associated with its diverse cellular roles in various human diseases including cancer and Alzheimer's disease (AD). In addition, keeping in view and advocating findings, a note on various phytochemicals and synthetic inhibitors, which are currently explored as therapeutic agents targeting functions of ENPP2 for the treatment of various human diseases is also presented. ? 2015 Bentham Science Publishers.