Browsing by Author "Kumar, Vinay"

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Advancements in the development of multi-target directed ligands for the treatment of Alzheimer's disease
(Elsevier Ltd, 2022-04-05T00:00:00) Kumar, Naveen; Kumar, Vijay; Anand, Piyush; Kumar, Vinay; Ranjan Dwivedi, Ashish; Kumar, Vinod
Alzheimer's disease (AD) is a multifactorial irreversible neurological disorder which results in cognitive impairment, loss of cholinergic neurons in synapses of the basal forebrain and neuronal death. Exact pathology of the disease is not yet known however, many hypotheses have been proposed for its treatment. The available treatments including monotherapies and combination therapies are not able to combat the disease effectively because of its complex pathological mechanism. A multipotent drug for AD has the potential to bind or inhibit multiple targets responsible for the progression of the disease like aggregated A?, hyperphosphorylated tau proteins, cholinergic and adrenergic receptors, MAO enzymes, overactivated N-methyl-D-aspartate (NMDA), ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor etc. The traditional approach of one disease-one target-one drug has been rationalized to one drug-multi targets for the chronic diseases like AD and cancer. Thus, over the last decade research focus has been shifted towards the development of multi target directed ligands (MTDLs) which can simultaneously inhibit multiple targets and stop or slow the progression of the disease. The MTDLs can be more effective against AD and eliminate any possibility of drug-drug interactions. Many important active pharmacophore units have been fused, merged or incorporated into different scaffolds to synthesize new potent drugs. In the current article, we have described various hypothesis for AD and effectiveness of the MTDLs treatment strategy is discussed in detail. Different chemical scaffolds and their synthetic strategies have been described and important functionalities are identified in the chemical scaffold that have the potential to bind to the multiple targets. The important leads identified in this study with MTDL characteristics have the potential to be developed as drug candidates for the effective treatment of AD. � 2022 Elsevier Ltd
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, Ashu
Purple 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).
Benzotriazole Substituted 2-Phenylquinazolines as Anticancer Agents: Synthesis, Screening, Antiproliferative and Tubulin Polymerization Inhibition Activity
(Bentham Science Publishers, 2022-10-28T00:00:00) Dwivedi, Ashish Ranjan; Rawat, Suraj Singh; Kumar, Vijay; Kumar, Naveen; Kumar, Vinay; Yadav, Ravi Prakash; Baranwal, Somesh; Prasad, Amit; Kumar, Vinod
Aims: Development of anticancer agents targeting tubulin protein. Background: Tubulin protein is being explored as an important target for anticancer drug development. Ligands binding to the colchicine binding site of the tubulin protein act as tubulin polymerization inhibitors and arrest the cell cycle in the G2/M phase. Objective: Synthesis and screening of benzotriazole-substituted 2-phenyl quinazolines as potential anticancer agents. Methods: A series of benzotriazole-substituted quinazoline derivatives have been synthesized and evaluated against human MCF-7 (breast), HeLa (cervical) and HT-29 (colon) cancer cell lines using standard MTT assays. Results: ARV-2 with IC50 values of 3.16 �M, 5.31 �M, 10.6 �M against MCF-7, HELA and HT29 cell lines, respectively displayed the most potent antiproliferative activities in the series while all the compounds were found non-toxic against HEK293 (normal cells). In the mechanistic studies involving cell cycle analysis, apoptosis assay and JC-1 studies, ARV-2 and ARV-3 were found to induce mitochondria-mediated apoptosis. Conclusion: The benzotriazole-substituted 2-phenyl quinazolines have the potential to be developed as potent anticancer agents. � 2023 Bentham Science Publishers.
Benzotriazole Substituted 2-Phenylquinazolines as Anticancer Agents: Synthesis, Screening, Antiproliferative and Tubulin Polymerization Inhibition Activity
(Bentham Science Publishers, 2022-10-28T00:00:00) Dwivedi, Ashish Ranjan; Rawat, Suraj Singh; Kumar, Vijay; Kumar, Naveen; Kumar, Vinay; Yadav, Ravi Prakash; Baranwal, Somesh; Prasad, Amit; Kumar, Vinod
Aims: Development of anticancer agents targeting tubulin protein. Background: Tubulin protein is being explored as an important target for anticancer drug development. Ligands binding to the colchicine binding site of the tubulin protein act as tubulin polymerization inhibitors and arrest the cell cycle in the G2/M phase. Objective: Synthesis and screening of benzotriazole-substituted 2-phenyl quinazolines as potential anticancer agents. Methods: A series of benzotriazole-substituted quinazoline derivatives have been synthesized and evaluated against human MCF-7 (breast), HeLa (cervical) and HT-29 (colon) cancer cell lines using standard MTT assays. Results: ARV-2 with IC50 values of 3.16 �M, 5.31 �M, 10.6 �M against MCF-7, HELA and HT29 cell lines, respectively displayed the most potent antiproliferative activities in the series while all the compounds were found non-toxic against HEK293 (normal cells). In the mechanistic studies involving cell cycle analysis, apoptosis assay and JC-1 studies, ARV-2 and ARV-3 were found to induce mitochondria-mediated apoptosis. Conclusion: The benzotriazole-substituted 2-phenyl quinazolines have the potential to be developed as potent anticancer agents. � 2023 Bentham Science Publishers.
Biotechnological attributes of biostimulants for relieving metal toxicity
(Elsevier, 2023-08-04T00:00:00) Rana, Varnika; Kumar, Adarsh; Singh, Reetu; Kumar, Vinay
A global scourge, heavy metals (HMs) toxicity with high concentration causes reactive oxygen species (ROS) to attack key biological molecules and has emerged in the past few years, posing a serious threat to human lives and ecosystems and agriculture. In plants, HMs alter the genome and genetic structure and eventually affect their protein and enzyme activities which further impede cellular metabolism. Therefore the growing body of scientific research is emphasizing green synthesis, that is, biostimulants use as the nexus of biotechnology and fertilizer that can be viewed as novel, efficient, eco-friendly, and cost-effective tools to safeguard the detrimental effects on ecosystems. In this regard, this chapter aims to scrutinize the role of various biostimulants against abiotic stresses using various biostimulants including seaweed extracts, protein hydrolysates, humic acids, and fulvic acids. The microbial-based stimulants are also discussed in this chapter. A list of biological processes has also been highlighted as prime targets for removing heavy metal(loid)s toxicity using biotechnological interventions. The biostimulants enhance growth and improve stress tolerance ability in plants. A table of targeted biotechnological attributes is also provided. Recently, a steep rise in interest in biostimulants is driving the development of sustainable green economics and agricultural concepts, while increasing demand for new products and understanding their mechanism of action is increasing. Further, the increasing demand for innovative biostimulants products and an interest in understanding their mechanisms of action will drive HM-free green economics and agricultural sustainability in the coming days. � 2023 Elsevier Inc. All rights reserved.
Biotechnological attributes of biostimulants for relieving metal toxicity
(Elsevier, 2023-08-04T00:00:00) Rana, Varnika; Kumar, Adarsh; Singh, Reetu; Kumar, Vinay
A global scourge, heavy metals (HMs) toxicity with high concentration causes reactive oxygen species (ROS) to attack key biological molecules and has emerged in the past few years, posing a serious threat to human lives and ecosystems and agriculture. In plants, HMs alter the genome and genetic structure and eventually affect their protein and enzyme activities which further impede cellular metabolism. Therefore the growing body of scientific research is emphasizing green synthesis, that is, biostimulants use as the nexus of biotechnology and fertilizer that can be viewed as novel, efficient, eco-friendly, and cost-effective tools to safeguard the detrimental effects on ecosystems. In this regard, this chapter aims to scrutinize the role of various biostimulants against abiotic stresses using various biostimulants including seaweed extracts, protein hydrolysates, humic acids, and fulvic acids. The microbial-based stimulants are also discussed in this chapter. A list of biological processes has also been highlighted as prime targets for removing heavy metal(loid)s toxicity using biotechnological interventions. The biostimulants enhance growth and improve stress tolerance ability in plants. A table of targeted biotechnological attributes is also provided. Recently, a steep rise in interest in biostimulants is driving the development of sustainable green economics and agricultural concepts, while increasing demand for new products and understanding their mechanism of action is increasing. Further, the increasing demand for innovative biostimulants products and an interest in understanding their mechanisms of action will drive HM-free green economics and agricultural sustainability in the coming days. � 2023 Elsevier Inc. All rights reserved.
Comparative Analysis of Metabolites in Contrasting Chickpea Cultivars
(Central University of Punjab, 2018) Ghosh, Alokesh; Kumar, Vinay
Phenolics are the major class of plant secondary metabolites. Among half of the plant phenolics are the flavonoids. The production of these metabolites induces during stresses and thus helps the plant to cope with the environment. Anthocyanins, a class of flavonoids protects plant from harmful UV rays, attracts the pollinators and seed dispersal, helps in mimicry and also helps in the root nodulation process in legumes. Chickpea is a leguminous and major pulse crop plant, shown in the winter season faces lots of stress. Anthocyanins and other phenolics help the plant to tolerate such stresses. Desi cultivars have more phenolics and anthocyanin as compared to the kabuli one. Flowers have higher concentration of anthocyanin than in leaves. Untargeted metabolomics profiling of the dry powdered mature seed samples of contrasting chickpea cultivars detects primary and secondary metabolites such as fatty acids, phenolics, phelols, terpenes, esters,sugar,etc in the seeds of chickpea.
The CRISPR–Cas9, genome editing approach: a promising tool for drafting defense strategy against begomoviruses including cotton leaf curl viruses
(Springer, 2019) Uniyal, A.P; Yadav, S.K; Kumar, Vinay
The CRISPR–Cas9 is emerging genome editing tool and very easy and straightforward in operation that has been tested and explored for introduction of new traits in plant systems. Recently, a number of reports have documented utilization of this technology for providing tolerance against viral diseases mediated by begomoviruses. Begomoviruses infect dicot and are transmitted by white flies and cause devastating losses to yield of important agricultural crops including tomato, cassava and cotton. An overview of genomic structure of begomoviruses has been presented to understand the potential strategy for designing of effective sgRNAs to combat the viral replication for generating resistance against infection. This review provides the introduction, recent developments, and applications of the CRISPR–Cas9 system in plants and proposes a holistic methodology for generating cotton plant an example having resistance against begomoviruses. The genome editing using CRISPR–Cas9 system against complex of begomoviruses collectively termed as cotton leaf curl virus, which a major contributor to reduction of the cotton yield especially in Northern India and Pakistan is also discussed thoroughly. In conclusion, this potential strategy could be a sustainable approach for development of tolerant crops against diseases mediated by DNA viruses. © 2019, Society for Plant Biochemistry and Biotechnology.
Current Approaches and Key Applications of Plant Metabolic Engineering
(Springer, 2018) Bharti; Reetu; Kumar, Vinay
The diversion of carbon flux toward biosynthesis of targeted products could be achieved by manipulation of targeted biosynthesis pathway in plants. This whole process consists of many steps in stepwise manners starting with the identification and isolation of targeted metabolites, elucidation of complete biosynthetic pathway for identification of point of intervention, discovery of corresponding potential metabolic genes, and overexpression of the selected genes in heterologous system and collectively production of the metabolites. The various biochemical processes including transcriptome, translatome, proteome, and reactome are being used to assist metabolic engineering by providing new insights into novel pathways or bottlenecks of existing pathways. Apart from all these, in-depth understanding of metabolic fluxes and feedback regulations is also mandatory for plant metabolic engineering. All these different current approaches are collectively considered for investigating the plant metabolic engineering to understand, reconstruct, analyze, and annotate the targeted pathways. The key applications of plant metabolic engineering have been compiled with a few important applications including improvement of nitrogen utilization in plant, development of highly nutritive food, and generation of biofuel production. In conclusion, the plant metabolic engineering could provide comprehensive evaluation of manipulation of biosynthetic pathways for numerous applications. This compiled information could act as a resource for crop breeding and biotechnology purposes.
Emerging trends in pest management in agriculture: Future perspectives
(CRC Press, 2023-09-06T00:00:00) Rattan, Rameswar Singh; Kumar, Vinay
Emerging trends in pest management in agriculture: Future perspectives
(CRC Press, 2023-09-06T00:00:00) Rattan, Rameswar Singh; Kumar, Vinay
Exogenous application of biostimulants for As stress tolerance in crop plants
(Elsevier, 2023-08-04T00:00:00) Garg, Tashima; Arora, Bhumika; Bokolia, Muskan; Joshi, Anjali; Kumar, Vinay; Kumar, Avneesh; Kaur, Simranjeet
Arsenic (As) is a nonessential toxic metalloid existing in two different inorganic forms: arsenite As (III) and arsenate As (V) which cause hindrance in plant developmental processes and are hazardous to human beings. As contamination is a major environmental issue as it stimulates physiological and metabolic dysfunctions, for instance, nutrient and redox imbalance, rate of photosynthesis, and membrane integrity, ultimately leading to reduced crop yield. Plants show detoxification processes to overcome As toxic effects by effluxing excess metal ions through metal transporters, accumulating As in the vacuole, and producing antioxidant enzymes. In recent times, the exogenous application of various biostimulants such as hormones, antioxidants, osmolytes, and others is being explored to combat As-mediating injuries to crop plants. These compounds are effective in improving seed germination, antioxidant enzyme activity, plant biomass, and overall growth of the plants. The objective of this chapter is to provide recent knowledge on the biostimulants hallmarks to alleviate As stress in crop plants. � 2023 Elsevier Inc. All rights reserved.
Exogenous application of biostimulants for As stress tolerance in crop plants
(Elsevier, 2023-08-04T00:00:00) Garg, Tashima; Arora, Bhumika; Bokolia, Muskan; Joshi, Anjali; Kumar, Vinay; Kumar, Avneesh; Kaur, Simranjeet
Arsenic (As) is a nonessential toxic metalloid existing in two different inorganic forms: arsenite As (III) and arsenate As (V) which cause hindrance in plant developmental processes and are hazardous to human beings. As contamination is a major environmental issue as it stimulates physiological and metabolic dysfunctions, for instance, nutrient and redox imbalance, rate of photosynthesis, and membrane integrity, ultimately leading to reduced crop yield. Plants show detoxification processes to overcome As toxic effects by effluxing excess metal ions through metal transporters, accumulating As in the vacuole, and producing antioxidant enzymes. In recent times, the exogenous application of various biostimulants such as hormones, antioxidants, osmolytes, and others is being explored to combat As-mediating injuries to crop plants. These compounds are effective in improving seed germination, antioxidant enzyme activity, plant biomass, and overall growth of the plants. The objective of this chapter is to provide recent knowledge on the biostimulants hallmarks to alleviate As stress in crop plants. � 2023 Elsevier Inc. All rights reserved.
Factors defining the effects of macromolecular crowding on dynamics and thermodynamic stability of heme proteins in-vitro,
(Elsevier, 2018) Kumar, Rajesh; Sharma, Deepak; Kumar, Vinay; Kumar, Rajesh
The role of crowding agents on structure and activities of heme proteins has been established. Analysis of kinetic and thermodynamic parameters measured for CO-dissociation reaction of natively-folded carbonmonoxycytochrome c (NCO) and carbonmonoxymyoglobin (MbCO) at different [GdnHCl] or [Urea] in the presence of crowding agents (dextran 40, dextran 70 and ficoll 70) demonstrate that (i) at low denaturant concentrations, crowder presence enhances the denaturant-mediated restricted dynamics of NCO and MbCO, and (ii) at higher denaturant concentrations, large scale unfolding-fluctuations dominate the dynamics and inclusion of crowder counteracts the structural-fluctuations causing the unfolding of proteins. Thermodynamic analysis of thermal and urea-unfolding curves of cytochrome c (Cyt c) and myoglobin (Mb) measured at different [GdnHCl] in presence of crowding agents reveals that crowder presence counterbalances and strengthens the destabilizing action of GdnHCl on stability of Cyt c and Mb, respectively. This study further demonstrates that the size, shape and concentration of crowding agent modulate the effect of crowder on denaturant-mediated dynamics and thermodynamic stability of heme proteins.
Factors Defining the Effects of macromolecularcrowding on dynamics and thermodynamics stability of heme proteins in-vitro
(Elsevier, 2018) Kumar, Rajesh; Sharma, Deepak; Kumar, Vinay; Kumar, Rajesh
The role of crowding agents on structure and activities of heme proteins has been established. Analysis of kinetic and thermodynamic parameters measured for CO-dissociation reaction of natively-folded carbonmonoxycytochrome c (NCO) and carbonmonoxymyoglobin (MbCO) at different [GdnHCl] or [Urea] in the presence of crowding agents (dextran 40, dextran 70 and ficoll 70) demonstrate that (i) at low denaturant concentrations, crowder presence enhances the denaturant-mediated restricted dynamics of NCO and MbCO, and (ii) at higher denaturant concentrations, large scale unfolding-fluctuations dominate the dynamics and inclusion of crowder counteracts the structural-fluctuations causing the unfolding of proteins. Thermodynamic analysis of thermal and urea-unfolding curves of cytochrome c (Cyt c) and myoglobin (Mb) measured at different [GdnHCl] in presence of crowding agents reveals that crowder presence counterbalances and strengthens the destabilizing action of GdnHCl on stability of Cyt c and Mb, respectively. This study further demonstrates that the size, shape and concentration of crowding agent modulate the effect of crowder on denaturant-mediated dynamics and thermodynamic stability of heme proteins.
First report on late Miocene (Tortonian: ~ 11�10�Ma) charophyte gyrogonites from Tapar, Kachchh District, Gujarat State, western India
(Springer Nature, 2022-09-05T00:00:00) Singh, Nongmaithem Amardas; Singh, Ningthoujam Premjit; Sharma, K. Milankumar; Patnaik, Rajeev; Tiwari, R.P.; Sehgal, Ramesh Kumar; Kumar, Vinay; Wazir, Wasim Abass; Singh, Y. Priyananda; Choudhary, Deepak
This paper describes the first record of charophyte gyrogonites from the late Miocene (Tortonian; ~ 11�10�Ma) Tapar locality of Kachchh, Gujarat State, western India. The recovered charophyte assemblage is constituted by Chara globularis var. aspera, C. globularis var. globularis, Lychnothamnus cf. sahnii, Lychnothamnus sp. and Nitellopsis sp. In addition, the present article discusses the palaeoenvironment based on the recorded charophyte gyrogonites (this study) and previously known faunal data (mainly vertebrates) from the Tapar locality, Kutch Basin, western India. Further, considering the significant extension of the biostratigraphic range [especially the First Appearance Datum (FAD)] of fauna from the Kutch Basin (in particular from the Tapar locality), we herein make an attempt to compare biostratigraphically the faunal assemblages from Kutch with those from the Siwalik Group, north India. � 2022, Indian National Science Academy.
Flavonoid accumulation as adaptation response in plants during abiotic stresses
(Routledge Taylor & Franchis Group, 2018) Rubal; Dhawan, Ashok; Kumar, Vinay
Flavonoids are secondary plant metabolites and are required for the proper growth and development of plants. Flavonoids also contribute by providing protection against adverse environmental conditions due to their antioxidant properties. The flavonoid biosynthetic pathway and its regulatory mechanism provide insight through the in-depth understanding of higher accumulation of flavonoid content required for growth and development and improved tolerance under abiotic stresses. The metabolic engineering of a selected set of biosynthetic pathway related genes has been achieved for providing better adaption under environmental constraints. The complied information could be exploited for the advancement of crop improvement programs under adverse environmental conditions by the accumulation of flavonoid contents.
Flavonoid Secondary Metabolite: Biosynthesis and Role in Growth and Development in Plants
(Springer, 2018) Kumar, Vinay; Suman, Upsana; Rubal; Yadav, Sudesh Kumar
Gene delivery methods: Advances and opportunities of nanoparticles-based techniques
(CRC Press, 2023-09-06T00:00:00) Borgohain, Venus; Swati, Z.Z.Z.; Reetu, Z.Z.Z.; Kumar, Vinay
Gene delivery methods: Advances and opportunities of nanoparticles-based techniques
(CRC Press, 2023-09-06T00:00:00) Borgohain, Venus; Swati, Z.Z.Z.; Reetu, Z.Z.Z.; Kumar, Vinay