Browsing by Author "Manoj Kumar Yadav"

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A knowledge-based approach for identification of drugs against vivapain-2 protein of Plasmodium vivax through pharmacophore-based virtual screening with comparative modelling
(Humana Press Inc., 2014) Manoj Kumar Yadav; Amisha Singh; D. Swati
Malaria is one of the most infectious diseases in the world. Plasmodium vivax, the pathogen causing endemic malaria in humans worldwide, is responsible for extensive disease morbidity. Due to the emergence of resistance to common anti-malarial drugs, there is a continuous need to develop a new class of drugs for this pathogen. P. vivax cysteine protease, also known as vivapain-2, plays an important role in haemoglobin hydrolysis and is considered essential for the survival of the parasite. The three-dimensional (3D) structure of vivapain-2 is not predicted experimentally, so its structure is modelled by using comparative modelling approach and further validated by Qualitative Model Energy Analysis (QMEAN) and RAMPAGE tools. The potential binding site of selected vivapain-2 structure has been detected by grid-based function prediction method. Drug targets and their respective drugs similar to vivapain-2 have been identified using three publicly available databases: STITCH 3.1, DrugBank and Therapeutic Target Database (TTD). The second approach of this work focuses on docking study of selected drug E-64 against vivapain-2 protein. Docking reveals crucial information about key residues (Asn281, Cys283, Val396 and Asp398) that are responsible for holding the ligand in the active site. The similarity-search criterion is used for the preparation of our in-house database of drugs, obtained from filtering the drugs from the DrugBank database. A five-point 3D pharmacophore model is generated for the docked complex of vivapain-2 with E-64. This study of 3D pharmacophore-based virtual screening results in identifying three new drugs, amongst which one is approved and the other two are experimentally proved. The ADMET properties of these drugs are found to be in the desired range. These drugs with novel scaffolds may act as potent drugs for treating malaria caused by P. vivax. © 2014 Springer Science+Business Media.
Anti-leishmanial activity of Ni(II), Pd(II) and Pt(II) β-oxodithioester complexes
(Royal Society of Chemistry, 2015) Manoj Kumar Yadav; Gunjan Rajput; Khushboo Srivastava; Rakesh K. Singh; Rajnikant Mishra; Michael G. B. Drew; Nanhai Singh
New functionalized planar β-oxodithioester cis-chelate complexes, [M(L)2] (L = L1, methyl-3-hydroxy-3-(p-bromophenyl)-2-propenedithioate, M = Ni 1, Pd 5, Pt 9; L2, methyl-3-hydroxy-3-(p-fluorophenyl)-2-propenedithioate, Ni 2, Pd 6, Pt 10; L3, methyl-3-hydroxy-3-(naphthyl)-2-propenedithioate, Ni 3, Pd 7, Pt 11; methyl-3-hydroxy-3-(p-methoxyphenyl)-2-propenedithioate, Ni 4, Pd 8, Pt 12), have been synthesized and characterized by elemental analysis, IR, UV-Vis, 1H and 13C NMR spectroscopy; the structures of 2-4, 8 and 11 have been elucidated by X-ray crystallography. In all crystal structures, the metal has four-coordinate slightly distorted square planar geometry with a cis-configuration of the ligands. These complexes have been assessed for their use as anti-leishmanial agents; 7 and 9 showed impressive anti-promastigote and anti-amastigote efficacy with IC50 values of 0.59 ± 0.10 μg mL-1, 0.56 ± 0.10 μg mL-1 and IC50 0.85 ± 0.27, 1.99 ± 0.08 μg mL-1, respectively. Cytotoxicity assays on both compounds displayed toxicity on the promastigotes but less toxicity against RAW 264.7 cell lines at different concentrations. The Pd and Pt complexes exhibit luminescent characteristics in solution, originating from the intraligand charge transfer state. © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2015.
Barrovian metamorphism of the metapelites in NE Sikkim (Eastern Himalaya): Constraints from chemographic projection and geothermobarometry
(Elsevier Ltd, 2021) Suparna Tewari; Divya Prakash; Manoj Kumar Yadav; Vedika Srivastava
The Sikkim Himalaya is mostly constituted of Proterozoic metapelites and metavolcanics of the Daling Group and high-grade gneisses and metasediments of the Darjeeling Group. Metapelitic schists and gneisses of the Sikkim Himalaya show an inverted sequence of metamorphic rocks ranging from lower greenschist facies (chlorite zone) to upper amphibolite facies (sillimanite + K-feldspar zone). The relative XMg in the minerals varies as: garnet > staurolite > biotite > muscovite. The P-T evolution of the study area has been constrained through the use of an internally consistent winTWQ programme and Perple_X software in the MnNCKFMASHTO model system. The combination of these two approaches demonstrates that the schists and gneisses have experienced a range of pressure and temperature with increasing grade. Constraints on the interpretation of mineral reactions and metamorphic history provided by pseudosection modelling for mineral proportions suggest the peak metamorphic temperature as ~750 °C and pressure ~7.5 kbar. The proposed prograde P-T path implies that the rocks from the study area may have resulted from a single metamorphic event with continuous changes in pressure and temperature. The conclusions made on the basis of the study of metamorphic event in the area and the regeneration of the reaction history adheres to classical Barrovian type metamorphism. The tectonic implication of such a metamorphic evolution is also discussed in the present work. Finally, we conclude that the possible explanation for the exhumation in this section of Himalaya may most likely be explained with the help of the channel flow model. © 2021 Elsevier Ltd
Current status of comparative genomics and inhibitors of plasmodium species: A systematic review
(International Journal of Pharma and Bio Sciences, 2016) Manoj Kumar Yadav; D. Swati; P.K. Patra
Malaria is still one of the most infectious and potentially lethal diseases known to mankind and typified by a series of intermittent fever episodes. This disease is responsible for high cases of mortality and morbidity in humans. The global incidence of malaria and its fatal consequences continue to be one of the worst catastrophes ever faced by mankind. P. falciparum, a parasitic protozoan, is responsible for a majority of malaria deaths. Another apicomplexan species, P. vivax, is the most widely distributed human malaria parasite infecting millions of individuals annually. Recently, P. knowlesi that normally infects long-tailed macaques also starts infecting humans. So, in-depth study of the pathogen is essential for combating the disease efficiently. Moreover, rise of drug-resistant cases in many areas, not only in developing countries but industrialized countries as well, during the past decade will make this situation more alarming. These situations, particularly the global resurgence of malaria and the rapid emergence of disease resistance, underscore the importance of the development of new antimalarial drugs. Achieving the goal of malariaelimination will depend on the existing knowledge and available new information of disease. Unfortunately, malaria is a disease of poverty, and despite a wealth of scientific knowledge there is insufficient market incentive to generate the competitive antimalarial drug research and development that is normally needed to deliver new products. In this review, we tried to show the comparative genomics-based status of malaria causing different Plasmodium pathogens and, effectiveness of available antimalarial drugs.
Discovery of novel inhibitors targeting Plasmodium knowlesi dihydrofolate reductase using molecular docking and molecular dynamics simulation
(Academic Press, 2021) Manoj Kumar Yadav; Manish Kumar Tripathi; Srishti Yadav
Plasmodium knowlesi, recognized as the fifth Plasmodium parasite, is the least studied malaria parasite. It is a significant cause of morbidity and mortality in the South-East Asia region. Enzymes of folate synthesis, especially dihydrofolate reductase (DHFR), is a well-approved drug target in other Plasmodium species, but its role in Plasmodium knowlesi is poorly studied. This work characterizes PkDHFR as a drug target and identifies inhibitors that can withstand the upcoming problem of resistance. The 3D structure of the PkDHFR target is modelled using comparative modelling, and further, it is refined and validated using energy minimization and torsional angle analysis methods. We extracted 13 compounds from DrugBank and ZINC databases using the “target similarity search” criteria. These compounds were categorized based on their binding affinity (−4.49 to −10.08 kcal/mol) and pose prediction against the active site of PkDHFR. Later on, the top 5 PkDHFR–compound complexes with high or equivalent binding affinity to its natural ligand (dihydrofolate) have undergone for dynamics. The simulation experiments reveal the higher stability of DB00563-PkDHFR complex and less conformational fluctuations and share a similar degree of compactness throughout the simulation trajectory. The MM/GBSA calculation of free energy of DB00563 is also the least (−72.84 kcal/mol) compared to others. Furthermore, the flexible side chain of DB00563 can bind and block the active site of PkDHFR more efficiently. Thus, the identified drug may be considered as a potential candidate for treating P. knowlesi malaria. © 2021 Elsevier Ltd
Drug target prioritization in Plasmodium Falciparum through metabolic network analysis, and inhibitor designing using virtual screening and docking approach
(2013) Manoj Kumar Yadav; Saurabh Kumar Pandey; D. Swati
The genome sequence of Plasmodium falciparum reveals that many metabolic pathways are unique as compared to its human host. Metabolic Network Analysis was carried out to find the essential enzymes critical for the survival of the pathogen. In the present study, choke point and load point analysis was used to locate putative targets. The identified targets were further checked to confirm that no alternate pathway or human homolog exists. Among the top 15 enzymes obtained from this analysis, we have selected P. falciparum orotidine-5'- monophosphate decarboxylase (PfODCase) enzyme as it is sequentially and structurally different from that of humans, for searching novel inhibitors. A five-point 3D pharmacophore was generated for the crystal structure of PfODCase complexes with uridine-5'-monophosphate (U5P). The binding site environment shows three H-bond acceptors, one H-bond donor and one negative ionizable feature. This pharmacophore model was used as a 3D query to perform virtual screening experiments against 2,664,779 standard lead compounds obtained from the freely available ZINC database. Top 10 hits obtained from virtual screening were selected for molecular docking experiments against PfODCase in order to verify their results and to have a better insight into their binding modes. Here, docking of U5P with PfODCase is used as a control. We have identified six compounds, among them, few are U5P analogs and others are novel ones with diverse scaffolds. The key residues: Lys42, Asp20, Lys72, Ser127, Ala184, Gln185 and Arg203 at the main binding pocket of PfODCase are responsible for better stability of diverse ligands. These compounds according to their free energy of binding could serve as potent leads for designing novel inhibitors against malarial ODCase enzyme. © 2013 Imperial College Press.
Endoscopic Third Ventriculostomy in Infants Less than One Year of Age: A Short Series of 14 Cases
(S. Karger AG, 2021) Sarita Chowdhary; Shyamendra Pratap Sharma; Pranaya Panigrahi; Manoj Kumar Yadav; Shiv Prasad Sharma
Background: Endoscopic third ventriculostomy (ETV) is currently considered as an alternative to cerebrospinal fluid (CSF) shunt systems in the treatment of obstructive hydrocephalus. This procedure allows the CSF to drain in the basal cisterns and reabsorbed by arachnoid granulations, and avoiding implantation of exogenous material. Aims and Objectives: The purpose of this study was to assess the success rate of ETV in infants less than 1 year of age with congenital noncommunicating hydrocephalus. Material and Methods: This study was a 2-year prospective study from August 2017 to July 2019. ETVs were performed in 14 patients younger than 1 year with diagnosis of noncommunicating hydrocephalous. A failure was defined as the need for shunt implantation after ETV. Phase-contrast MRI of the brain was done after 6 months to see patency of ETV fenestration and CSF flow through ventriculostomy. Results: ETV was tried in 18 patients and successfully performed in 14 patients. Out of the 14 patients, shunt implantation after ETV was performed in 3 patients (failed ETV). In the successful cases, etiology was idiopathic aqueductal stenosis in 8, shunt complications in 2, and 1 case was a follow-up case of occipital encephalocele; the mean age was 7.7 months (range 3-12). In the 3 failed cases, etiology was aqueductal stenosis, mean age was 7.6 months (range 3-11). In all ETVs, failed patients MPVP shunting was done. Follow-up of nonshunted patients was done from 6 to 24 months (mean 15 months). There was no mortality or permanent morbidity noted following ETV. Conclusion: ETV is a good surgical procedure for less than 1-year-old children. © 2021 S. Karger AG. All rights reserved.
Fundamentals of molecular modeling in drug design
(Elsevier, 2022) Manish Kumar Tripathi; Shaban Ahmad; Rashmi Tyagi; Vandana Dahiya; Manoj Kumar Yadav
The advent of high-performance computing has increased the role of computer application as a tool for in silico experiments in all research areas, including drug discovery. This chapter describes the current status of the computer application in drug discovery using molecular modeling as a tool. Molecular modeling is an essential tool for drug discovery and has developed enormously with increasing the computational power and biological information of active compounds. The current modeling techniques fasten the drug discovery and design strategy. The most widely application of molecular modeling includes the target structure prediction associated with disease, identifying new drug molecules for disease therapeutics, and designing/proposing new chemical entities. This introductory chapter outlines the fundamental methods of molecular modeling such as docking, pharmacophore modeling, virtual screening, protein structure modeling, and artificial intelligence approach of drug design. It also gives an overview of the basic algorithms and principles behind the modeling tools and thermodynamics approaches used in drug discovery. Thus, it set up the foundation of the molecular modeling approach used in drug design for the researchers. © 2022 Elsevier Inc. All rights reserved.
Impact of ligand framework on the crystal structures and luminescent properties of Cu(I) and Ag(I) clusters and a coordination polymer derived from thiolate/iodide/dppm ligands
(American Chemical Society, 2015) Gunjan Rajput; Manoj Kumar Yadav; Michael G. B. Drew; Nanhai Singh
New homoleptic hexanuclear Ag(I) and heteroleptic trinuclear Cu(I) clusters and a Cu(I) coordination polymer (CP) of the formulas [Ag6(dtc)6] 1, [Cu3I2(dppm)3(dtc)] 2, and [Cu(ttc)I]- 3 (dtc = N-methylbenzyl-N-methyl-thiophenedithiocarbamate; dppm = 1,1-bis(diphenylphosphino)methane; and ttc = dimethyltrithiocarbonate) were synthesized and characterized by elemental analysis, IR, UV-vis, 1H, 13C, and 31P NMR spectroscopies, and their structures were elucidated by X-ray crystallography. The complexes show interesting structures and luminescent properties. Complex 1, which is centrosymmetric, contains four short Ag···Ag interactions at 2 × 2.966(1) and 2 × 3.014(1) Å. There are also several Ag···Ag distances of 3.3-3.4 Å. The molecule shows hexagonal orientation with alternating silver and sulfur atoms of the overlapping Ag3S3 hexagons in the front and rear, along the a axis. Complex 2 is a rare trinuclear cluster complex of Cu(I); the Cu···Cu distances are 2.906(2), 3.551(2), and 3.338(2) Å, the foremost representing a substantial intermetallic contact. The Cu3I2P6S2 core is comprised of three fused distorted hexagonal rings with the I1 atom located at the center participating in all three rings. Complex 3 is an iodide-bridged CP with a "staircase"-like arrangement in which the Cu(I) is tetrahedrally surrounded by a sulfur atom from the ttc ligand and three iodine atoms. Unlike 3, which is nonluminescent, 1 and 2 are strongly luminescent in the solid and solution at room temperature. The time-resolved emission spectra reveal a triexponential decay curve and short mean lifetime characteristic of fluorescence behavior. Diffuse reflectance spectroscopy revealed semiconducting behavior with band gaps of 2.12, 3.01, and 2.18 eV for 1-3, respectively. © 2015 American Chemical Society.
In Silico Study of Variable Surface Proteins in Plasmodium Species: Perspectives in Drug Design
(International Association of Scientists in the International Association of Scientists in the, 2016) Manoj Kumar Yadav; D. Swati
The variable surface proteins expressed by P. falciparum and P. vivax are transported to the surface of infected erythrocyte and are exposed to the host immune system. The possibility of using variable surface proteins as a common drug target has been analyzed in both the Plasmodium species. Sequence analysis of variable surface proteins showed a low-level conservation within as well as between the species. Amino acid composition analysis revealed higher frequency of hydrophilic amino acids as compared with that of hydrophobic residues. In order to gain more insight into their diverse functional role, the three-dimensional structure was predicted using comparative modeling approach. These models were evaluated and validated by checking stereochemistry of underlying amino acids. Structural alignment of variable surface proteins by superimposing them shows less conservation. Due to differences at sequence as well as structural level, the variable surface proteins are expected to show difference in their degree of invasiveness. These differences were also cross-examined by evolutionary study, and the results obtained were in accordance with the aforesaid study. The existence of structural differences noticed in the present study showed that the variable surface proteins could not be used as a common drug target in both the malarial species. Therefore, species-specific strategy may be followed for drug targeting against variable surface proteins of P. falciparum and P. vivax. © 2015, International Association of Scientists in the Interdisciplinary Areas and Springer-Verlag Berlin Heidelberg.
Influence of the ligand frameworks on the coordination environment and properties of new phenylmercury(II) β-oxodithioester complexes
(Royal Society of Chemistry, 2015) Gunjan Rajput; Manoj Kumar Yadav; Michael G. B. Drew; Nanhai Singh
New phenylmercury(ii) complexes of the form [PhHg(L1), PhHg(L2) and PhHg(L3)] (L1 = methyl-3-hydroxy-3-(p-methoxyphenyl)-2-propenedithioate (1), L2 = methyl-3-hydroxy-3-(p-bromophenyl)-2-propenedithioate (2) and L3 = methyl-3-hydroxy-(3-pyridyl)-2-propenedithioate (3)) have been synthesized and characterized by elemental analysis, IR, UV-Vis, 1H and 13C NMR. The crystal structures of 1-3 reveal a linear geometry about the mercury atom via ipso-C and S11 atoms. 1 and 2 exhibited O,S-coordination whereas 3 preferred S,S-coordination. Intramolecular Hg⋯O bonding interactions are also observed in 1 and 2 at distances of 2.638(14), 2.644(10) Å respectively. However in 3, incorporation of the 3-pyridyl substituent on the ligand enhanced the proximity of S13 and N14, giving rise to significant intramolecular Hg⋯S and intermolecular Hg⋯N interactions at 3.141(5) Å and 2.77(2) Å respectively generating a 1-D polymeric chain motif. The O,S- or S,S-coordination preference and Hg⋯N interactions have been assessed by DFT calculations. All the complexes show metal perturbed ligand-centred luminescence characteristics in solution and in the solid phase. The band gap values 2.54, 2.66 and 2.61 eV for 1, 2 and 3, respectively, evaluated from the diffuse reflectance spectroscopy show the semiconducting nature of the complexes. © The Royal Society of Chemistry 2015.
Metamorphic P–T evolution of Hercynite-quartz-bearing granulites from the Diwani Hill, North East Gujarat (NW India)
(Elsevier B.V., 2021) Divya Prakash; Manish Kumar; Swapnil Kumar Rai; Chandra Kant Singh; Saurabh Singh; Roopali Yadav; Srishti Jaiswal; Vedika Srivastava; Manoj Kumar Yadav; Sourav Bhattacharjee; Pradip Kumar Singh
Diwani Hill granulites occurring on the southern tip of the South Delhi Terrane (SDT) of Aravalli Mobile Belt (AMB), comprises rocks of granulite facies and represent the deeper level of the crust. The SDT represents an admixture of charnockites, granites, calc-granulites and hercynite-quartz-bearing pelitic granulites. The symplectite and corona textures recorded in the hercynite-quartz-bearing granulites from a part of SDT provides a wide spectrum of P-T sensors in support of the petrological evolution. P-T evolution of these hercynite-quartz-bearing granulites has been constrained through the use of THERMOCALC program, conventional thermobarometry, and pseudosection modelling in the NCKFMASHTO model system using Perple_X software. The unification of these three calculations, demonstrates that the hercynite-quartz-bearing granulites experienced peak pressure and temperature at 6.7 kbar and 750 °C, respectively. The textural imprints, multistage reaction textures, P-T pseudosections as well as the application of multi-equilibrium calculation give evidence for decompressive history related to their exhumation. SHRIMP U-Pb chronological results yield ages between 780 and 680 Ma as a time of metamorphic overprint, and the ages between 1591 and 1216 Ma corresponding with detritus derived from magmatic source for hercynite-quartz-bearing granulites. Zircon ages reflect that continental crust in the SDT resulted from the Mesoproterozoic protolith of an igneous origin whereas sedimentary succession was deposited between 1216 and 780 Ma. The present study envisages that the South Delhi basin would have been a remnant of the proto-Mozambique Ocean in NW India which was closed due to subduction. This subduction metamorphosed the sediments of the basin to granulite facies and the rocks were subsequently, uplifted because of the thrust sheet tectonics during the Neoproterozoic times. © 2020 Elsevier B.V.
Metamorphic zonal sequences of pelitic schists and gneisses from the area around Kandra (Jharkhand): Constraints from field and textural relationship
(Geological Society of India, 2017) Divya Prakash; Dhananjay Kumar Patel; Suparna Tewari; Manoj Kumar Yadav; Roopali Yadav
The pelitic schists of the area around Kandra, Singhbhum district, Jharkhand belong to the Chaibasa Formation of the Singhbhum Group, which constitute a part of the youngest Precambrian orogenic cycle of the Singhbhum region. Structurally, the area represents the Singhbhum anticlinorium and is overlain by Dalma traps which form the synclinorium towards the north of the area around Kandra. This area mainly consists of medium to high grade rocks belonging to greenschist and amphibolite facies. These rocks are folded in the E-W trending doubly plunging folds (F1) overturned towards the south with low plunges and superposed by cross-folds (F2). The spatial distribution of the index minerals in the pelitic schists of the area shows Barrovian type of metamorphism. Four isograds, viz. biotite, garnet, staurolite and sillimanite have been delineated by the first appearance of the index minerals and also by isograd reactions. The textural relation suggests that sillimanite is formed from staurolite consumption reaction instead of kyanite consumption. © 2017, Geological Society of India.
New planar trans-copper(II) β-dithioester chelate complexes: synthesis, characterization, anticancer activity and DNA-binding/cleavage studies
(Taylor and Francis Ltd., 2017) Manoj Kumar Yadav; Akhilendra Kumar Maurya; Gunjan Rajput; Krishna Kumar Manar; Manjula Vinayak; Michael G. B. Drew; Nanhai Singh
New planar trans-copper(II) β-dithioester complexes, [Cu(L)2] (L = methyl-3-hydroxy-(3-pyridyl)-2-propenedithioate (L1 in 1), methyl-3-hydroxy-(2-naphthyl)-2-propenedithioate (L2 in 2), methyl-3-hydroxy-3-(p-methoxyphenyl)-2-propenedithioate (L3 in 3), methyl-3-hydroxy-3-(p-fluorophenyl)-2-propenedithioate (L4 in 4), and methyl-3-hydroxy-3-(p-bromophenyl)-2-propenedithioate (L5 in 5)), have been synthesized and characterized by elemental (C, H, N and S) analysis, ESI-MS, IR, and UV-vis spectra. The structures of HL3 and its corresponding complex 3 have been determined by X-ray crystallography. Electrochemical behavior of all complexes has been studied by cyclic voltammetry. All five planar complexes show efficient DNA-binding and DNA (PBR322)-cleavage in a concentration-dependent manner (1 > 3 > 5 > 2 > 4). Cleavage efficiency is enhanced in the presence of H2O2 as well as ascorbic acid. However, the order of increased efficiency of Cu(II) chelates differs in the presence of H2O2 as 4 > 1 > 2 > 3 > 5. Among these complexes, the pyridyl- and methoxy-functionalized 1 and 3 have shown higher self-activating capability in DNA-cleavage. All complexes show significant variation in IC50 on MCF-7 cell line. Additionally, treatment with the complexes gradually increases apoptotic cell death in dose-dependent manner in RAW 264.7 cell line. These findings highlight potential cancer protective nature of these complexes. © 2017 Informa UK Limited, trading as Taylor & Francis Group.
Novel Insights into Understanding the Molecular Dialogues between Bipolaroxin and the Gα and Gβ Subunits of the Wheat Heterotrimeric G-Protein during Host–Pathogen Interaction
(MDPI, 2022) Deepti Malviya; Udai B. Singh; Budheswar Dehury; Prakash Singh; Manoj Kumar; Shailendra Singh; Anurag Chaurasia; Manoj Kumar Yadav; Raja Shankar; Manish Roy; Jai P. Rai; Arup K. Mukherjee; Ishwar Singh Solanki; Arun Kumar; Sunil Kumar; Harsh V. Singh
Spot blotch disease of wheat, caused by the fungus Bipolaris sorokiniana (Sacc.) Shoem., produces several toxins which interact with the plants and thereby increase the blightening of the wheat leaves, and Bipolaroxin is one of them. There is an urgent need to decipher the molecular interaction between wheat and the toxin Bipolaroxin for in-depth understanding of host–pathogen interactions. In the present study, we have developed the three-dimensional structure of G-protein alpha subunit from Triticum aestivum. Molecular docking studies were performed using the active site of the modeled G-protein alpha and cryo-EM structure of beta subunit from T. aestivum and ‘Bipolaroxin’. The study of protein–ligand interactions revealed that six H-bonds are mainly formed by Glu29, Ser30, Lys32, and Ala177 of G-alpha with Bipolaroxin. In the beta subunit, the residues of the core beta strand domain participate in the ligand interaction where Lys256, Phe306, and Leu352 formed seven H-bonds with the ligand Bipolaroxin. All-atoms molecular dynamics (MD) simulation studies were conducted for G-alpha and -beta subunit and Bipolaroxin complexes to explore the stability, conformational flexibility, and dynamic behavior of the complex system. In planta studies clearly indicated that application of Bipolaroxin significantly impacted the physio-biochemical pathways in wheat and led to the blightening of leaves in susceptible cultivars as compared to resistant ones. Further, it interacted with the Gα and Gβ subunits of G-protein, phenylpropanoid, and MAPK pathways, which is clearly supported by the qPCR results. This study gives deeper insights into understanding the molecular dialogues between Bipolaroxin and the Gα and Gβ subunits of the wheat heterotrimeric G-protein during host–pathogen interaction. © 2022 by the authors.
Occurrence of sapphirine-bearing granulites from Kothuru, Eastern Ghats Mobile Belt: implications on ultra-high temperature metamorphism
(Indian Academy of Sciences, 2022) Saurabh Singh; Divya Prakash; Chandra Kant Singh; Vedika Srivastava; Manoj Kumar Yadav; Pradip Kumar Singh; Manish Kumar
In this study, we present evidence for the stable coexi-stence of sapphirine + quartz and the compositional characteristics of the sapphirine-bearing granulites from Kothuru in the Eastern Ghats Mobile Belt (EGMB), India. The study area is an integral part of the Precambrian terrane in the western part of EGMB and is characterized by the granulite facies rocks comprising mainly of pelitic granulites such as char-nockites, enderbites, leptynites, khondalites and gneisses, and sapphirine–spinel–quartz-bearing rocks. The chemistry of the minerals present in the assem-blage has been examined using the electron probe micro analyser to infer their occurrence and distribu-tion in various reaction textures observed during the petrographic study. The peak and post-peak history of the sapphirine-bearing granulites of Kothuru section have been constrained in the NCKFMASHTO system showing decompressional P–T path of high-grade metamorphic rocks through the intersection of the iso-pleth contours of various mineral phases present. The proposed P–T path with a steep isothermal decompres-sion retrograde trajectory may be attributed to the over-thrust processes. The results obtained from the petrographic study of the mineral assemblages along with their textural relationship, mineral chemistry, especially Fe3+/FeTotal ratio and pseudosection model-ling reveal that the studied segment has arrested promising ultra-high temperature metamorphic signa-tures and is tectonically distinct from those reported in the adjacent areas. © 2022. Current Science. All Rights Reserved.
Rare intermolecular M⋯H-C anagostic interactions in homoleptic Ni(ii)-Pd(ii) dithiocarbamate complexes
(Royal Society of Chemistry, 2015) Manoj Kumar Yadav; Gunjan Rajput; Lal Bahadur Prasad; Michael G. B. Drew; Nanhai Singh
New functionalized homoleptic dithiocarbamates of the form [M(L)2] (M = Ni(ii), L = L1, N-(3-methoxybenzyl)-N-(methylbenzyl)dithiocarbamate (1), L3, N-(3,4,5-trimethoxybenzyl)-N-(3-methylpyridyl)dithiocarbamate (3), L4, N-(4-methoxybenzyl)-N-benzyldithiocarbamate (4); Pd(ii), L2, N-(N′-methyl-2-pyrrole)-N-benzyldithiocarbamate (2)) have been synthesized and characterized by microanalysis and their structures have been investigated using X-ray crystallography. All the four structures are centrosymmetric with the metal located in a square plane with minor distortions, Pd(ii) greater than Ni(ii). The crystal structures of 1 and 2 revealed the existence of unique intermolecular C-H⋯M (Ni, Pd) anagostic interactions between the methylene hydrogen atom on the ligand substituents and the metal centres and these enable the formation of 1-D polymeric chains. Particularly, geometric parameters (Pd⋯H-C = 2.61 Å; ∠Pd⋯H-C = 173°) for the C-H⋯Pd interactions in 2 are at the border of anagostic and hydrogen bonding. By contrast, 4 shows interactions between the methylene hydrogen atom and the CS2Ni ring rather than the metal alone, while the interaction in 3 is intermediate between the two aforementioned types. These interactions are not shown in solution as revealed by their 1H NMR studies. DFT calculations have been performed to analyse these rare interactions. 1, 3 and 4 are weakly conducting, σrt = 10-10-10-12 S cm-1, and show semiconductor behaviour in the 313-373 K range. © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2015.
Regulation of Transcription Factors in Abscisic Acid-Mediated Signaling Under Abiotic Stresses
(CRC Press, 2025) Varsha Rani; Ramwant Kumar Gupta; Manoj Kumar Yadav; Rajesh Kumar Singh; D. L. Yadav
Abiotic stresses like drought, salinity, heat, cold, and osmotic pressure have adverse effects on a plant’s growth and development. The stress response in plants is mediated by several signaling pathways, mediated by the intervention of different phytohormones. The phytohormones that are linked to biotic and abiotic stresses are salicylic acid, jasmonic acid, auxin, abscisic acid, and gibberellin. The role of auxins, cytokinins, ethylene, gibberellins, brassinosteroids, and jasmonic acid has been studied in the context of developing abiotic stress-tolerant plants by metabolic engineering. The phytohormone abscisic acid (ABA) is a key hormone known to be involved in the regulation of abiotic stresses. ABA regulates osmolytes and detoxifies reactive oxygen species (ROS) as part of stress signaling pathways. During abiotic stress, signaling and plant response, phytohormones induce the expression of the transcription factors that regulate stress-responsive genes. Over the past few years, several transcription factors (TF) have been identified and are essential for regulating plant responses to these stresses. Activation of these TF can be ABA-dependent or independent in nature. In plants, several transcription factors like NAC, NAM, NF-Y, WRKY, bZIP, MYC, MYB, NAM, DREB, AP2, YABBY, Zinc finger, and their cis-acting elements regulate abiotic stresses in association with different plant hormones. This chapter highlights the ABA-dependent and independent transcription factors responsible for abiotic stress tolerance and their regulatory mechanisms. © 2026 selection and editorial matter, Kapil Gupta, Keshawanand Tripathi, Amit Joshi, and Dinesh Yadav.
Revolutionizing Technology with Spintronics: Devices and Their Transformative Applications
(Elsevier Ltd, 2024) Manoj Kumar Yadav; Ramesh Kumar; Ratneshwar Kumar Ratnesh; Jay Singh; Ramesh Chandra; Abhishek Kumar; Vishal Vishnoi; Gajendra Singh; Ashish Kumar Singh
The scaling of metal oxide semiconductor field effect transistors (MOSFETs) for data storing and logic circuit operation has reached a critical point, beyond which further scaling poses various secondary issues. These problems include short channel effects, hot carrier effects (HCEs), and reliability concerns. However, a promising alternative called spintronics has recently emerged as a highly exciting technology. Spintronics considers both the charge and spin of electrons in device operations and offers superior properties compared to MOSFETs. Researchers have reported numerous spintronics devices that exhibit significant potential in memory and logic circuits when integrated with complementary metal oxide semiconductor (CMOS) technology. These devices not only possess excellent scalability but also consume less power than MOSFETs at the nano-scale level. This article aims to provide a comprehensive review of the current state, future prospects, and challenges associated with spintronics devices. © 2024 Elsevier B.V.
Synthesis, characterization, DNA binding and cleavage activity of homoleptic zinc(II) β-oxodithioester chelate complexes
(Taylor and Francis Ltd., 2017) Manoj Kumar Yadav; Akhilendra Kumar Maurya; Gunjan Rajput; Krishna Kumar Manar; Manjula Vinayak; Michael G. B. Drew; Nanhai Singh
New homoleptic zinc(II) complexes, [Zn(L)2], where L = methyl-3-hydroxy-(3-pyridyl)-2-propenedithioate L1 1, and methyl-3-hydroxy-(4-pyridyl)-2-propenedithioate L2 2, have been synthesized and characterized by elemental (C, H, and N) analysis, ESI-MS, and (IR, UV–vis, NMR) spectroscopy; the structure of 1 has been deduced by X-ray crystallography. The DNA binding and cleavage activity of the complexes have been studied. The cleavage potential of pBR322 DNA by 1 and 2 has been checked. Complex 1, which contains nitrogen of the pyridine group in the 3-position enhances DNA cleavage potential in the presence of ascorbic acid; however, the complex is protective against DNA cleavage in the presence of DMSO or H2O2. Also, 1 causes cytotoxicity against the MCF-7 breast cancer cell line. The efficient cytotoxic activity and DNA cleavage ability of 1 in the presence of ascorbic acid shows its potential anticancer properties and the need for further investigations of its potential as an anticancer drug. © 2017 Informa UK Limited, trading as Taylor & Francis Group.