School Of Basic And Applied Sciences
Permanent URI for this communityhttps://kr.cup.edu.in/handle/32116/17
Browse
625 results
Search Results
Item DNA Barcoding, Phylogeny and Phylogeography of Green Sea Weed Ulva from Indian Subcontinent(Central University of Punjab, 2019) Rani, Pooja; Bast, FelixItem In silico identification of natural anticancer product and their efficacy in breast cancer cells and cancer stem like cells(Central University of Punjab, 2020) Kushwaha, Prem Prakash; Kumar, ShashankBreast cancer is the most commonly diagnosed lethal cancer in women worldwide. Notch signaling pathway is directly linked to breast cancer recurrence and aggressiveness. Natural remedies are becoming a prime choice to overcome against cancer due to lesser side effect and cost-effectiveness. Literature survey and in silico study identified Bulbine frutescens (Asphodelaceae), Kurarinone (KU) and 3-O-(E)-p- coumaroylbetulinic acid (CB) as lead plant product/phytochemicals. Methanolic and hexane extract of B. frutescens (BME and BHE respectively), KU and CB were studied for their anticancer activity and notch signaling pathway inhibitory potential in breast cancer cells. Moreover, KU and CB were also studied for their effect in mammosphere. Literature-based identification of methanol soluble phytochemicals of B. frutescens and in silico docking study revealed Bulbineloneside D as a potent notch signaling inhibitor (ϒ-secretase). In silico docking potential of KU and CB were equal to standard gamma secretase inhibitor DAPT (-8.74 kcal/mol). KU-gamma secretase complex showed lower RMSD value, marginal fluctuation in Radius of gyration (Rg), more number of inter hydrogen bonding, and stable secondary structure of the protein which indicates KU as candidate gamma secretase inhibitor (GSI). B. frutescens extracts (IC50 4.8– 28.4 μg/ml), Kurarinone (IC50 0.43-3.42 µM) and CB (IC50 0.99-5.88 µM) significantly decreased cell viability in MDA-MB-231 and T47D cells in time dependent manner. B. frutescens, KU and CB induced cell cycle arrest at G1 phase in MDA-MB-231 and T47D cells. RT-PCR analysis of cell cycle (cyclin D1, CDK4, and p21) and apoptosis modulating genes (caspase 3, Bcl2 and survivin) revealed upexpression of p21, and caspase 3, and down expression of cyclin D1, CDK4, Bcl2 and survivin genes in test extract/phytochemicals treated breast cancer cells. Western Blot analysis showed reduced expression of cyclin D1 and increased procaspase 3 protein expression in extract/phytochemicals treated breast cancer cells in time dependent manner. Fluorescence spectrophotometry and confocal microscopy showed extract/phytochemicals induced nuclear morphology and mitochondrial integrity disruption, and increased reactive oxygen species production in MDA-MB-231 and T47D cells at IC50 and sub IC50 concentration. Flow cytometric apoptosis analysis of extract/phytochemicals treated MDA-MB-231 cells showed significant increase in early apoptotic population in comparison to non-treated cells at IC50 and sub IC50 (half of the IC50) concentration. Dual-Luciferase Reporter assay confirmed notch promoter inhibitory activity of B. frutescens, Kurarinone and CB in HEK293 transfected cells at IC50 concentration. Moreover, RT-PCR analysis showed down regulation of notch responsive genes (Hes1 and Hey1) at transcription levels in extract/phytochemical treated breast cancer cells in time dependent manner. Western Blot analysis showed reduced notch responsive protein (Hes1, Hey1 and E-cadherin) expression in extract/phytochemical treated breast cancer cells. KU and CB treatment decreased the mammosphere formation ability in MCF-7 cells at IC50 concentration by lowering the notch signaling target proteins (Hes1, Hey1, and E-cadherin) and proteins involved in cancer cell self-renewal (c-Myc, SOX-2, CD44). In conclusion, extract/phytochemicals have cell cycle arrest, ROS production, apoptosis induction, and mitochondria membrane potential disruption efficacy in breast cancer cells. KU and CB have the ability to downregulate the notch signaling pathway in breast cancer and cancer stem like cells.Item Design, Synthesis and Evaluation of Donepezil-Rasagiline Based Compounds as Multipotent Inhibitors for the Treatment of Alzheimer’s Disease(Central University of Punjab, 2019) Kumar, Bhupinder; Kumar, VinodAlzheimer’s disease (AD) is multifactorial in nature and different enzymes including MAO, AChE, and amyloid beta are implicated in its pathogenesis. The pathomechanism of AD is complex in nature and single target drugs proved to be ineffective for the treatment of the disease. With an aim of developing dual/multipotent inhibitors, 4,6- diphenylpyrimidines were optionally substituted with propargyl group and an ethyl chain containing a cyclic or acyclic tertiary nitrogen atom (piperidine/morpholine/pyrrolidine/N,N-dimethyl) as potential pharmacophores for MAO and AChE enzymes. Compound VB1 was found to be the most potent MAO-A (IC50 value of 18.34 ± 0.38 nM) inhibitor and VB8 was found to be the most potent AChE (IC50 value of 9.54 ± 0.07 nM) inhibitor. Compound VB3 was another promising compound in series-I with IC50 values of 28.33 ± 3.22 nM and 18.92 ± 0.29 nM against MAO-A and AChE, respectively and displayed very high selectivity index (103) for AChE over BuChE. These compounds were found to be reversible inhibitors of MAO and AChE enzymes and non-toxic to the human neuroblastoma SH-SY5Y cells. Based on structure-activity relationship analysis of the first series of compounds, second series of the compounds were designed by fixing the position of piperidine/morpholine ethyl chain at the para position of one of the phenyl rings. In the second series, compound VP15 v was found to be a multi-potent inhibitor of MAO-B and AChE with IC50 values of 0.37 ± 0.03 μM and 0.04 ± 0.003 μM, respectively. VP15 was found to be selective for MAOB with selectivity index of 270 over MAO-A. It also displayed SI of 625 for AChE over BuChE. VP15 was found to be irreversible inhibitor of MAO-B. In the third series of target compounds, both the phenyl rings of diphenylpyrimidines were substituted with O-propargyl groups. Different derivatives have been synthesized with O-propargyl groups substituted at ortho, meta and para positions of the phenyl rings. In the third series of compounds, AVB1 and AVB4 were found to be the most potent inhibitors of AChE and MAO-B with IC50 values of 1.35 ±0.03 μM and 1.49 ± 0.09 μM, respectively. In the reversible inhibition studies, the lead compounds were found to be reversible inhibitors of MAO-B and AChE enzymes. In the ROS protection inhibition studies, AVB1 and AVB4 displayed good activity in SH-SY5Y cells and AVB1 reduced the ROS levels up to 30% at 5 μM. This series of compounds were also found to be non-toxic to the SH-SY5Y cells in the cytotoxicity studies. Thus, from the present study it can be concluded that 4,6-diphenylpyrimidine derivatives can act as potential lead for the development of effective drug candidates for the treatment of AD. Compound VB3 and VP15 were found to be the most potent dual inhibitors of MAO and AChE.Item DNA barcoding and phylogeny based comparative evaluation of anti-cancer properties of Caulerpa (J V Lamouroux) spp. from Indian coasts(Central University of Punjab, 2019) Mehra, Richa; Bast, Felix and Singh, SandeepA total of 15 Caulerpa samples were collected from Indian coasts and identified based on morphological and molecular data inferred from ITS, 18S, tufA and rbcL. Seven different species viz. C. scalpelliformis, C. racemosa, C. sertularioides, C. verticillata, C. taxifolia, and C. corynephora; and their geographical isolates were identified. Barcode data for these species was generated using aforementioned molecular markers and used for phylogenetic assessment. Phylogenetic trees using Bayesian inference (BI) and Maximum Likelihood (ML) function were generated for each molecular marker. tufA was found to be most suitable marker for the genus Caulerpa, resolving the species into 17 different lineages, with 15 corresponding to already known sections and 2 new lineages. Besides, a database named DbIndAlgae of Indian algae was generated and all the morphological as well as molecular data generated in this study is uploaded on the database. In addition, the phycochemical analysis revealed the presence of alkaloids, terpenoids, steroids, tannins, saponins, flavonoids, and phenols in different Caulerpa species. The selective cytotoxicity of methanolic extracts of Caulerpa (CMEs) was evaluated on MDA-MB-231, T47-D and H1299 cells, and the results revealed significant cytotoxicity of all species. C. racemosa KNY-254 and C. taxifolia TEN-158 were found to be most potent on MDA-MB-231 cells with IC50 value of 0.226 ± 0.004 and 0.246 ± 0.009 µg/µL. The mitochondrial membrane perturbation was revealed by JC-1 and apoptotic cell death was confirmed by Annexin V/FITC staining. CMEs also induced ROS in MDA-MB-231 cells as depicted by DHE, and increased activity of SOD, decreased activity of gluthatione reductase. The CMEs also exhibit anti-invasion activity and inhibited up to 71% migration across the artificially scratched wound in MDA-MB-231, w.r.t. untreated control cells. Moreover, chemical probing of C. racemosa KNY-254 by LC-MS analysis revealed six previously reported and six unreported molecules. The molecular docking analysis revealed weak to moderate interactions with all of the protein targets viz. Bcl2, AMPK, mTOR, BID, PERK, IGF-1R, PI3K, PTP1B and Akt2, known to play important role in cancer cell signaling. Additionally, a moderately positive correlation amongst the phylogeny and anti-cancer activity was observed suggesting that phylogeny might provide cues for anti-cancer activity, subject to further validations.Item Transcriptomic investigations of gene networks in response to arsenic accumulation in Brassica juncea (L.) Czern & Coss(Central University of Punjab, 2019) Thakur, Sapna; Bhardwaj, PankajArsenic (As), a widespread toxic metalloid is class I carcinogen known to cause adverse health effects in human. In the present study, As accumulation potential and differential gene expression in B. juncea is investigated. The amount of arsenic accumulated varied in the range of 15.99 to 1138.70 mg/Kg on dry weight basis in five cultivars. A decrease in chlorophyll content and increase in membrane damage and enzymatic activities of antioxidants was observed with increase in As concentration in the B. juncea cultivars. Using maximum As accumulating cultivar (RLM514), a total of 10,870 significantly differentially expressed transcripts in response to As treatment were identified. Further, the pathway analysis revealed a large scale reprogramming of genes involving carbon metabolism (2.5%), plant hormone signaling (1.4%), and glutathione metabolism (0.6%). Moreover, a comparative account of Cd toxicity revealed a total of 11,294 transcripts to be significantly differentially expressed. The genes related to response to chemical, oxidative stress, transport, and secondary metabolism were upregulated whereas multicellular organismal development, developmental process, photosynthesis were downregulated by Cd treatment. Furthermore, 616 membrane transport proteins were found to be significantly differentially expressed. Cd-related transporters such as metal transporter (Nramp1), metal tolerance protein (MTPC2, MTP11), cadmiumtransporting ATPase, and plant cadmium resistance protein (PCR2, PCR6) were upregulated while cadmium/zinc- transporting ATPase (HMA2, HMA3, HMA4), highaffinity calcium antiporter (CAX1), and iron transport protein (IRT1) were downregulated by Cd treatment. Pathway analysis revealed signaling cascades including plant hormones signaling, MAPK signaling and Ca signaling was modulated suggesting their role in Cd-stress tolerance. The regulation overview using MapMan also revealed gene expression related to plant hormones, calcium regulation and MAP kinases were altered under Cd-stress.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 Electrochemical performance of a self-assembled two-dimensional heterostructure of rGO/MoS2/h-BN(Royal Society of Chemistry, 2020) Alegaonkar, A.P; Alegaonkar, P.S; Pardeshi, S.K.We report the preparation and electrochemical performance evaluation of a two-dimensional (2D) self-assembled heterostructure of graphene oxide (rGO), molybdenum disulphide (MoS2), and hexagonal boron nitride (h-BN). In the present study, the rGO-MoS2-h-BN (GMH) multi-layered GMH heterostructure is fabricated via an in situ chemical route. Based on material analysis, the composite consists of bond conformations of C-B-C, Mo-S, C-N, B-N, and Mo-C, indicating the layered stacks of rGO/h-BN/MoS2. In electrochemical analysis, the composite showed superior performance in the aqueous medium of cobalt sulphate (CoSO4) over other samples. CV measurements, performed over the range 10 to 100 mV s-1, showed a change in specific capacitance (Csp) from 800 to 100 F g-1. GMH showed almost no degradation up to 20?000 cycles @ 100 mV s-1. The calculated Csp, energy density (ED), and power density (PD) are discussed in light of Nyquist, Bode, and Ragone analysis. An equivalent circuit is simulated for the cell and its discrete electronic components are discussed. Due to its larger effective electron diffusion length > 1000 ?m, broadly, the composite showed battery-like characteristics, as supported by radical paramagnetic resonance and transport response studies. The symmetric electrodes prepared in one step are facile to fabricate, easy to integrate and involve no pre or post-treatment. They possess superior flat cell character, are cost effective, and are favourable towards practicality at an industrial scale, as demonstrated on the laboratory bench. The details are presented. The Royal Society of Chemistry.Item Anti-cancer drug doxorubicin induced cardiotoxicity: Understanding the mechanisms involved in ros generation resulting in mitochondrial dysfunction(Rasayan Journal of Chemistry, c/o Dr. Pratima Sharma, 2020) Upadhayay, S; Sharma, N; Mantha, A.K; Dhiman, M.Doxorubicin (DOX), despite being an effective anti-cancer drug has offsite targets that affect the vital organs such as heart, brain and kidney. DOX-induced cardiotoxicity is reported as a multi-factorial process that interferes with mitochondrial bioenergetics. These responses increase the threshold of oxidant-mediated injury and redox-mediated apoptosis in the cardiomyocytes. Oxidative stress particularly mitochondrial dysfunction in cardiomyocytes associated with cardiovascular diseases. In the present study we examined the effect of DOX on H9c2 cardiomyocyte where cells were treated with 5 μM DOX. To rule out the source of reactive oxygen species (ROS) during DOX-induced toxicity, the DOX-treated cardiomyocytes were incubated with 100 ?M diphenyleneiodonium (DPI), 50 μM salicyl hydroxamic acid (SHX), 20 μM Carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (FCCP), which are specific inhibitors of NADPH oxidase (NOX), Myeloperoxidase (MPO), and mitochondrial oxidative phosphorylation respectively and 10 μM N-acetyl cysteine (NAC, free radical scavenger) was also used to perceive the role of ROS. H2O2 (100 ?M) treated H9c2 cardiomyocytes were used as positive controls. The cell viability, reactive oxygen species (ROS) level and oxidative stress were determined using MTT assay, NBT assay/Flow-cytometry and Western blotting based assays. The effect of DOX on mitochondria was evaluated using Amplex Red assay; fluorescent probes such as MitoSOX and MitoTracker were used to examine the DOX-induced ROS production from the mitochondrial matrix. The mitochondrial membrane potential was evaluated using JC-1 dye. Western blotting was performed for cytochrome c release and apoptosis was examined with Annexin V-FITC assay. DOX was found to reduce cell viability, increase ROS level followed by enhanced oxidative stress in the form of protein carbonyls. DOX also showed a reduction in the mitochondrial membrane potential and allowed the release of cytochrome c which further leads to apoptosis and cell death. Further to rule out the pathway/mechanism(s) of DOX-mediated cardiac pathologies, the treatment with inhibitors of the classical ROS sources such as NADPH oxidase, Myeloperoxidase, mitochondria and general ROS scavenger (NAC) suggested that ROS via NOX and MPO during DOX-induced toxicity plays a crucial role in cardiomyocytes. The mitochondrial integrity was conserved when the cells were treated with NOX and MPO inhibitors, the cytochrome C release and apoptosis reduced in presence of these inhibitors. Taken together, these results demonstrate that DOX leads to ROS production and oxidative stress in cardiomyocytes which ultimately affects the mitochondrial integrity and functions, most importantly the ROS released via NOX and MPO is critical during DOX-induced cardiotoxicity. - RAS?YAN. All rights reserved.Item A glimpse on all-solid-state Li-ion battery (ASSLIB) performance based on novel solid polymer electrolytes: a topical review(Springer, 2020) Arya, A; Sharma, A.L.All-solid-state batteries are swiftly gaining the attention of the research community owing to their widespread applications in electric vehicles, digital electronics, portable appliances, etc. A battery comprises three components: cathode, anode and electrolyte. An electrolyte is the heart of the battery and plays a crucial role in the overall performance of the battery. In order to make the review more focused, all-solid-state Li-ion batteries (ASSLIBs) have been considered. This review covers the architecture of ASSLIBs, advantages, and characteristics of the solid polymer electrolytes. The important preparation methods are summarized, followed by the characterizations for testing the suitability of electrolytes for solid-state batteries. The discussion is focused on the "state of the art" in the field of solid-state batteries, device fabrication, and comparison in terms of capacity, energy density, and cyclic stability. In the last section, the ion conduction mechanism in different solid polymer electrolytes is discussed. Finally, it is tried to give a possible outlook for developing future hybrid and multifunctional electrolytes which can act as a bridge for developing solid-state batteries covering a broad range of applications. - 2020, Springer Science+Business Media, LLC, part of Springer Nature.Item CuO Nanoparticles as a Simple and Efficient Green Catalyst for the Aziridine Ring-Opening: Examination of a Broad Range of Nucleophiles(Wiley-Blackwell, 2020) Chatterjee, R; Santra, S; Chakraborty, Ghosal N; Giri, K; Zyryanov, G.V; Majee, A.It has been observed that CuO nanoparticles act as effective and reusable catalyst for the ring-opening reaction of aziridines with a wide range of nucleophiles such as alcohols, thiols, and indoles. The catalytic activity has been tested in large scale reactions. The methodology is applicable in very low catalyst loading. The reaction proceeds under solvent-free conditions. The catalyst has been used for six consecutive cycles with comparable efficiency. The present methodology could be considered as environmentally benign as indicated by the calculation of E-factors which are very low in the range of 0.37-1.31. - 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim