School Of Basic And Applied Sciences
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Item Chitosan-supported FeCl3 catalyzed multicomponent synthesis of tetrahydroisoquinoline-indole hybrids with promising activity against chloroquine resistant Plasmodium falciparum(Elsevier B.V., 2022-10-26T00:00:00) Kaur, Pavneet; Sharma, Priyanka; Kumar, Vinod; Sahal, Dinkar; Kumar, RakeshAn operationally simple three-component coupling of tetrahydroisoquinoline (THIQ), aldehydes and indoles or indole-3-carboxylic acids has been achieved using chitosan-ionic liquid supported FeCl3 (chit-IL@FeCl3) as a recyclable heterogeneous catalyst. The developed waste-free approach provided rapid access to biologically important THIQ-indole hybrids without the use of any additive or ligand. The synthesized THIQ-indole hybrids were evaluated as antiplasmodial agents against chloroquine-sensitive (Pf3D7) and chloroquine-resistant (PfINDO) strains of Plasmodium falciparum. Compounds 4b (most potent against Pf3D7) and 4g (most potent against PfINDO) showed IC50 values of 1.32 and 0.26 �g/mL respectively. Also, 4g showed strong cytocidal action against both rings and trophozoite stages. Furthermore, cytotoxic study against human liver HUH 7 cells revealed that the most potent compound 4g with an excellent resistance index of 0.07 is also relatively non-toxic. The results of this study suggest that THIQ-indole hybrids hold an enormous potential for developing new antimalarial agents with novel mechanism of action. � 2022 Elsevier B.V.Item Anticancer Activities of Plant Secondary Metabolites: Rice Callus Suspension Culture as a New Paradigm(Elsevier B.V., 2020-12-17T00:00:00) Ramakrishna, Wusirika; Kumari, Anuradha; Rahman, Nafeesa; Mandave, PallaviPlant natural products including alkaloids, polyphenols, terpenoids and flavonoids have been reported to exert anticancer activity by targeting various metabolic pathways. The biological pathways regulated by plant products can serve as novel drug targets. Plant natural compounds or their derivatives used for cancer treatment and some novel plant-based compounds which are used in clinical trials were discussed. Callus suspension culture with secondary metabolites can provide a continuous source of plant pharmaceuticals without time and space limitations. Previous research has shown that rice callus suspension culture can kill >95% cancer cells with no significant effect on the growth of normal cells. The role of candidate genes and metabolites which are likely to be involved in the process and their potential to serve as anticancer and anti-inflammatory agents were discussed. Large scale production of plant callus suspension culture and its constituents can be achieved using elicitors which enhance specific secondary metabolites combined with bioprocess technology. � 2020Item Synthesis, biological evaluation and molecular modeling studies of phenyl-/benzhydrylpiperazine derivatives as potential MAO inhibitors.(Elsevier, 2018) Kumar, Bhupinder; Sheetal; Mantha, Anil K.; Kumar, VinodMonoamine oxidase inhibitors (MAOIs) are potential drug candidates for the treatment of various neurological disorders like Parkinson's disease, Alzheimer's disease and depression. In the present study, two series of 4-substituted phenylpiperazine and 1-benzhydrylpiperazine (1-21) derivatives were synthesized and screened for their MAO-A and MAO-B inhibitory activity using Amplex Red assay. Most of the synthesized compounds were found selective for MAO-B isoform except compounds 3, 7, 8, 9 and 13 (MAO-A selective) while compound 11 was non-selective. In the current series, compound 12 showed most potent MAO-B inhibitor activity with IC50 value of 80 nM and compound 7 was found to be most potent MAO-A inhibitor with IC50 value of 120 nM and both the compounds were found reversible inhibitors. Compound 8 was found most selective MAO-A inhibitor while compound 20 was found most selective inhibitor for MAO-B isoform. In the cytotoxicity evaluation, all the compounds were found non-toxic to SH-SY5Y and IMR-32 cells at 25 µM concentration. In the ROS studies, compound 8 (MAO-A inhibitor) reduced the ROS level by 51.2% while compound 13 reduced the ROS level by 61.81%. In the molecular dynamic simulation studies for 30 ns, compound 12 was found quite stable in the active cavity of MAO-B. Thus, it can be concluded that phenyl- and 1-benzhydrylpiperazine derivatives are promising MAO inhibitors and can act as a lead to design potent, and selective MAO inhibitors for the treatment of various neurological disorders.Item Cytotoxic activity of saragassum wightii on pc-3 cancer cell-line(Central University of Punjab, 2012) Jahid, Mohd.; Bast, FelixFinding novel antitumor compounds with low side effects could be an interesting proposal. Antioxidant and anticancer potentials of seaweed extracts can possibly be explored for developing the new anticancer drugs. Polyphenols are extensively distributed in seaweeds and these are reported to be free radical scavengers. This study was designed to check the cytotoxic potential of the methanolic and hydromethanolic extracts from the brown algae S. wightii. The total phenolic content in the hydromethanolic extract and the methanolic extract of S. wightii was determined by the Folin-Ciocalteu method. The total phenolic content in methanolic extract was found to be greater than hydromethanolic extract. The percentage inhibition or scavenging activity of both the extracts was calculated by using the DPPH assay and was more for the methanolic extract. PC-3 cancer cell-line was used as an experimental model. The methanolic crude extract is significantly cytotoxic against the PC-3 cancer cells. On the other hand the hydromethanolic crude extract was not found to be the significantly cytotoxic against the PC-3 cancer cells.Item Chemical composition and antiproliferative, antioxidant, and proapoptotic effects of fruiting body extracts of the lingzhi or reishi medicinal mushroom, ganoderma lucidum (Agaricomycetes), from India(Begell House Inc., 2016) Gill, B.S.; Sharma, P.; Navgeet, Kumar, S.Ganoderma lucidum is a renowned medicinal mushroom exploited as a panacea because of the broad spectrum of its bioactivities, which give it invaluable nutritional and clinical implications. This research was implemented with an incentive to explore and quantify various macromolecules encompassed in the oriental fungus; these vary in concentration with respect to the development/growth phase, host plants, and geographic location of collection. Chemical profiling of G. lucidum confirmed the presence of myco-constituents, their amounts varying in response to extreme climatic conditions. G. lucidum extract exhibited elevated levels of all myco-constituents but flavonoids, which were more pronounced when in a parasitic relationship with their host plants. Proapoptotic efficiency portrayed by the extracts against a prostate cancer cell line (PC-3) was also found to be similar. The samples collected from the Bathinda region, with Azadirachta and Acacia trees as the host plants, showed several-fold augmentation in levels of G. lucidum gredients compared with other variants. Elevated levels of myco-constituents highlight their significance in inhibiting prostate cancer cell proliferation, reducing reactive oxygen species, suppressing invasive potential, and inducing apoptosis. It was thus concluded that G. lucidum grown on Azadirachta plants was more efficient in exhibiting potent biological activities than G. lucidum grown on other host plants. ? 2016 Begell House, Inc.Item Cellular uptake, intracellular trafficking and cytotoxicity of silver nanoparticles(2012) Singh, R.P.; Ramarao, P.Silver nanoparticles (Ag NPs) are used in consumer products and wound dressings due to their antimicrobial properties. However, in addition to toxic effects on microbes, Ag NPs can also induce stress responses as well as cytotoxicity in mammalian cells. We observed that Ag NPs are efficiently internalized via scavenger receptor-mediated phagocytosis in murine macrophages. Confocal and electron microscopy analysis revealed that internalized Ag NPs localize in the cytoplasm. Ag NPs cause mitochondrial damage, induce apoptosis and cell death. These effects were abrogated in presence of Ag ion-reactive, thiol-containing compounds suggesting the central of Ag ions in Ag NP toxicity. Quantitative image analysis revealed that intracellular dissolution of Ag NPs occurs about 50 times faster than in water. In conclusion, we demonstrate for the first time that Ag NPs are internalized by scavenger receptors, trafficked to cytoplasm and induce toxicity by releasing Ag ions. ? 2012 Elsevier Ireland Ltd.Item Amino acid functionalized zinc oxide nanostructures for cytotoxicity effect and hemolytic behavior: Theoretical and experimental studies(Elsevier Ltd, 2017) Singh, Satvinder; Singh, Baljinder; Sharma, Prateek; Mittal, Anu; Kumar, Sanjeev; Saini, G.S.S.; Tripathi, S.K.; Singh, Gurinder; Kaura, AmanBlending of theoretical and experimental approach, provide an important strategy in designing the nanostructure at a microscopic level and helps in predicting the response of synthesized material towards inhibition of the growth of breast cancer cell. In this work, ab initio calculations using super cell approach are performed for three different amino acids (AAs)-Histidine (His), Arginine (Arg) and Aspartic acid (Asp) coated Zinc oxide (ZnO) nanostructures to explain the growth mechanism of nanoparticles (NPs) of different shapes. Based on the first principles calculations, we reveal that ZnO-AA (Arg and Asp) NPs results in rod like and ZnO-His NPs lead to tablet like configuration. Similar morphologies are fabricated using AAs through synthetic route. The effect of concentration ratio of reactants and pH has been studied. As synthesized samples, are characterized by using Transmission Electron Microscopy (TEM), X-ray diffraction (XRD), Fourier Transform Infrared (FTIR) and UV?Vis spectroscopy techniques. Based on the results, a plausible mechanism of formation of nanostructures has been proposed. The nanostructures with rod like morphology are found to be biocompatible with normal red blood cells and show cytotoxic effect as evaluated from hemolysis and cytotoxicity assays on breast (MCF-7, T47D, MDA-MB-231) & prostate cancer (PC-3) cell lines. ? 2017 Elsevier LtdItem Anthocyanins enriched purple tea exhibits antioxidant, immunostimulatory and anticancer activities(Springer India, 2017) Joshi, Robin; Rana, Ajay; Kumar, Vinay; Kumar, Dharmesh; Padwad, Yogendra S.; Yadav, Sudesh Kumar; Gulati, AshuPurple coloured tea shoot clones have gained interest due to high content of anthocyanins in addition to catechins. Transcript expression of genes encoding anthocyanidin reductase (ANR), dihydroflavonol-4-reductase (DFR), anthocyanidin synthase (ANS), flavonol synthase (FLS) and leucoantho cyanidin reductase (LAR) enzymes in three new purple shoot tea clones compared with normal tea clone showed higher expression of CsDFR, CsANR, CsANS and lower expression of CsFLS and CsLAR in purple shoot clones compared to normal clone. Expression pattern supported high content of anthocyanins in purple tea. Four anthocyanins (AN1?4) were isolated and characterized by UPLC-ESI-QToF-MS/MS from IHBT 269 clone which recorded highest total anthocyanins content. Cyanidin-3-O-?-d-(6-(E)-coumaroyl) glucopyranoside (AN2) showed highest in vitro antioxidant activity (IC50?DPPH?=?25.27???0.02??g/mL and IC50?ABTS?=?10.71???0.01??g/mL). Anticancer and immunostimulatory activities of cyanidin-3-glucoside (AN1), cyanidin-3-O-?-d-(6-(E)-coumaroyl) glucopyranoside (AN2), delphinidin-3-O-?-d-(6-(E)-coumaroyl) glucopyranoside (AN3), cyanidin-3-O-(2-O-?-xylopyranosyl-6-O-acetyl)-?-glucopyranoside (AN4) and crude anthocyanin extract (AN5) showed high therapeutic perspective. Anthocyanins AN1?4 and crude extract AN5 showed cytotoxicity on C-6 cancer cells and high relative fluorescence units (RFU) at 200??g/mL suggesting promising apoptosis induction activity as well as influential immunostimulatory potential. Observations demonstrate potential of purple anthocyanins enriched tea clone for exploitation as a nutraceutical product. ? 2017, Association of Food Scientists & Technologists (India).Item High-throughput virtual screening, identification and in vitro biological evaluation of novel inhibitors of signal transducer and activator of transcription 3(Birkhauser Boston, 2015) Singh, Pushpendra; Bast, FelixSignal transducer and activator of transcription (STAT) family, encompassing protein molecules that function as a second messenger and transcription factor, are famously known to regulate a multitude of cellular processes including inflammation, cell proliferation, invasion, angiogenesis, metastasis and immune system homeostasis. STAT3 is one of the six members of a family of transcription factors. STAT3 has proved themselves to be interesting candidates for anticancer therapy as they are over-expressed in most cancer cells. Thus, we studied receptor-based molecular docking of STAT3 against natural compounds and further validations of lead molecules in an array of cancer cells. In the present study, we screened approximately 50,000 natural compounds from the IBS. All natural compounds were docked with the X-ray crystal structure of STAT3 (PDB; 1BG1) retrieved from the protein data bank by using Maestro 9.6 (Schr?dinger Inc). First, we performed high-throughput virtual screening of IBS against the SH2 domain of STAT3. Further, best 20 compounds that possess minimal Gscore along with 85 natural compounds that had been reported in published literature as having anticancer properties were selected, and molecular docking was performed using the XP (extra precision) mode of GLIDE. We analyzed Gscore and protein-ligand interactions of top ranking compounds. It was discovered in this study, compounds CID252682, CID5281670 (Morin), CID5281672 (Myricetin), CID72277 (Epigallocatechol) and CID65064 (Epigallocatechin Gallate, EGCG) yielded the excellent dock score with the STAT3 concluded with the help of docking-free energy. Moreover, IBS STOCK1N-43090, STOCK1N-66505, STOCK1N-54303, STOCK1N-44634, STOCK1N-45027, STOCK1N-73784, STOCK1N-69597, STOCK1N-73062, STOCK1N-81915 and STOCK1N-70844 have better docking-free energy. Further, we chose EGCG and myricetin compounds, and their effect on biological activity such as cell proliferation, oxidative stress, colony formation, mRNA expression of STAT3, and cell number was reported after the 48 h treatments in cancer cell lines. EGCG and myricetin reduce the STAT3 mRNA expression confirmed by RTPCR. Moreover, EGCG and myricetin reduce cell proliferation and ROS generation after 48 h treatments. Interestingly, our result also indicates that the reduction in potential for colony formation enhances anti-metastasis activity of EGCG and myricetin. The information obtained from our study assisted us in drawing a more lucid picture regarding the existence STAT3 natural compounds inhibitor on diverse cancer cells. ? 2015 Springer Science+Business Media.Item Intracellular delivery of redox cycler-doxorubicin to the mitochondria of cancer cell by folate receptor targeted mitocancerotropic liposomes(2012) Malhi, Sarandeep Singh; Budhiraja, Abhishek; Arora, Sumit; Chaudhari, Kiran R.; Nepali, Kunal; Kumar, Raj; Sohi, Harmik; Murthy, Rayasa S.R.Cancer cells reflect higher level of ROS in comparison to the normal cell, so they become more vulnerable to further oxidative stress induced by exogenous ROS-generating agents. Through this a novel therapeutic strategy has evolved, which involves the delivery of redox cycler-doxorubicin (DOX) to the mitochondria of cancer cell where it acts as a source of exogenous ROS production. The purpose of this study is to develop a liposomal preparation which exhibits a propensity to selectively target cancer cell along with the potential of delivering drug to mitochondria of cell. We have rendered liposomes mitocancerotropic (FA-MTLs) by their surface modification with dual ligands, folic acid (FA) for cancer cell targeting and triphenylphosphonium (TPP) cations for mitochondria targeting. The cytotoxicity, ROS production and cell uptake of doxorubicin loaded liposomes were evaluated in FR (+) KB cells and found to be increased considerably with FA-MTLs in comparison to folic acid appended, mitochondria targeted and non-targeted liposomes. As confirmed by confocal microscopy, the STPP appended liposomes delivered DOX to mitochondria of cancer cell and also showed higher ROS production and cytotoxicity in comparison to folic acid appended and non-targeted liposomes. Most importantly, mitocancerotropic liposomes showed superior activity over mitochondria targeted liposomes which confirm the synergistic effect imparted by the presence of dual ligands - folic acid and TPP on the enhancement of cellular and mitochondrial delivery of doxorubicin in KB cells. ? 2012 Elsevier B.V. All rights reserved.