Browsing by Author "Ranjeet Kumar"

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A Case of Folding Pattern in Flexible Tripodal of N-Substituted Bisethylenamine Bridged Pyridazinone Dimers
(Wiley-Blackwell, 2017) Ranjeet Kumar; Archana Gaurav; Shiv Pal; Ashish Kumar Tewari
Present manuscript reports three tripodal molecules for their special structural and conformational properties. Interestingly, X-ray structure revealed that all these molecules adopt folded conformation in solid state. Further, these molecules are flexible due to linker, may exist in various conformations, the studies have been carried out with different conformers through theoretical calculation in gaseous state. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
An Experimental and Theoretical Study of the Conformational Stability of Triazinone Fleximers: Quantitative Analysis for Intermolecular Interactions
(John Wiley and Sons Inc, 2023) Akhilesh Kumar; Praveen Singh; Ranjeet Kumar; Priyanka Yadav; Amit Jaiswal; Ashish Kumar Tewari
Synthesis and characterization of triazinone based propylene linked phthalimide and benzimidazole have been carried out for conformational analysis and the study of their quantitative intermolecular interactions. The conformational analyses have been calculated by X-ray crystallography in the solid state and theoretical calculations in the gaseous state. From the crystal structure and theoretical calculations we have found that all compounds are stable in the folded conformation. These stable conformations are stabilized by different intra and intermolecular interactions, such as C−H⋯O, C−H⋯N, C−H⋯π and π⋯π. Quantitative intermolecular interactions and interactions energy calculations of both compounds have been carried out by Hirshfeld surface analysis. © 2023 Wiley-VCH GmbH.
CCSO nano catalyzed solid phase synthesis of 3-oxo-5,6-disubstituted-2,3-dihydropyridazine-4-carbonitrile
(Royal Society of Chemistry, 2014) Praveen Singh; Ranjeet Kumar; Brijesh Kumar Yadav; Ranjana S. Khanna; Ashish Kumar Tewari
Co-doped Ce0.94Ca0.05Sr0.01O1.94 (CCSO) nano particles have been successfully synthesized by an auto-combustion method and were characterized by XRD, TEM and AFM analyses. The catalytic activity of the nano-catalyst is evaluated by the synthesis of substituted pyridazines from substituted benzil and cyano acetylhydrazide, which have great biological and pharmaceutical interest. Thus, a highly economically efficient one-pot solvent free synthesis of pyridazine was developed, which is promoted by the CCSO nano catalyst. The benefits of the reaction are its very short time (2-4 min) and high yields (90-95%). The method offers a highly convergent, inexpensive, and functionality-tolerable procedure for rapid access to important pyridazine compounds in good yields. This journal is © the Partner Organisations 2014.
Characterization of filarial phosphoglycerate kinase
(Elsevier B.V., 2019) Ranjeet Kumar; Faiyaz Ahmad; Sushma Rathaur
Phosphoglycerate kinase (PGK) is a key enzyme of glycolysis which also acts as a mediator of DNA replication and repair in the nucleus. We have cloned and expressed PGK in Brugia malayi. The rBmPGK was found to be 415 amino acid residues long having 45 kDa subunit molecular weight. This enzyme was also identified in different life stages of bovine filarial parasite Setaria cervi. The enzyme activity was highest in microfilarial stage followed by adult female and male as also shown by real time PCR in the present study. Further using BmPGK primers the cDNA prepared from S. cervi was amplified and sequenced which showed 100% homology with Brugia malayi PGK. B. malayi and S. cervi, PGK consists of conserved calmodulin binding domain (CaMBD) having 21 amino acids. In the present study we have shown the CaMBD binds to calcium-calmodulin and regulates its activity. The binding of calmodulin (CaM) with CaMBD was confirmed using calmodulin agarose binding pull down assay, which showed that the rBmPGK binds to CaM agarose-calcium dependent manner. The effect of CaM-Ca2+on the activity of rBmPGK was studied at different concentration of CaM (0.01–5.0 μM) and calcium chloride (0.01–100 μM). The rBmPGK was activated up to 85% in the presence of CaM at 1 μM and 10 μM concentration of CaCl2. Interestingly this activation was abrogated by metal chelator EDTA. Similar results were shown in case of Setaria cervi PGK. A significant increase (90 ± 10) % in ScPGK activity was observed in the presence of CaM and CaCl2 at 1.0 μM and 1.0 mM respectively, further increase in the conc. of CaCl2, the activity of ScPGK was found to be decreased like rBmPGK. Bioinformatics studies have also confirmed the interaction between CaMBD and CaM which showed CaM interacted to Phe 206, Gln 220, Arg 223 and Asn 224 of rBmPGK CaM binding domain. On the basis of these findings, it has been suggested that the activity of filarial PGK could be regulated in cells by Ca2+-CaM depending upon the concentration of calcium. To the best of our knowledge this is first report in filarial parasite. © 2019 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM)
Conformational Studies of Triazole Based Flexible Molecules: A Comparative Analysis of Crystal Structure and Optimized Structure for DNA Binding Ability
(Wiley-Blackwell, 2017) Ranjeet Kumar; Pratima Yadav; Shiv Pal; Krishnan R. Kumar; Balasubramanian Sridhar; Ashish K. Tewari
The present studies deal with design and synthesis of triazole based flexible molecules, their conformational analysis and DNA binding ability. The conformational studies were carried out in solid state through crystal structure and in gaseous state through theoretical calculation. The obtained conformations, found from either crystal structure or optimized most stable conformation from theoretical calculation have been screened for DNA binding ability to find importance of conformation in flexible organic molecules. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Design, synthesis, and molecular modeling of heterodimer and inhibitors of α-amylase as hypoglycemic agents
(Institute for Ionics, 2023) Ved Prakash Singh; Manisha Nidhar; Pratima Yadav; Ranjeet Kumar; Priyanka Sonker; Ashish Kumar Tewari
A series of rosiglitazone-based heterodimers were designed and synthesized, and their α-amylase and antioxidant activity was evaluated. The binding mode of the compounds at the active site of PPARγ and α-amylase enzyme was explored using MolDock docking method. In molecular docking studies against crystal structure of PPARγ (PDB code: 1FM6), compounds 10 and 13 showed interaction with amino acids Arg379, Asp379, Asn385, Ala387, Glu388, Val389, Glu390, and Lys438. Docking results of α-amylase enzyme (PDB code: 5EOF) with compounds 10 and 13 showed excellent interaction with amino acids Ala169, Lys172, Asp173, Tyr174, Val175, Arg176, and Lys178. Depending on the docking score, the designed compounds were selectively prioritized for synthesis. All synthesized compounds were subjected to in vitro α-amylase activity and antioxidant activity. Compounds 10 and 13 were to possess higher potency than acarbose, and most of the compounds showed antioxidant activity. Additionally, the most active compound 10 was evaluated for in vivo anti-diabetic activity. Graphical abstract: [Figure not available: see fulltext.]. © 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Design, Synthesis, in Silico and in Vitro Dipeptidyl Peptidase-4 Activity of Triazole-Based Heterocyclic Compounds
(John Wiley and Sons Inc, 2025) Ranjeet Kumar; Manisha Nidhar; Ashish Kumar Tewari
1,2,3-triazole-based ring connected with pyridazine, triazine, methyl pyrazole, diphenyl pyrazole, and phthalimide moieties through propylene linker has been synthesized for antidiabetic evaluation via click chemistry. The antidiabetic evaluations have been done by molecular docking studies and in-vitro tests against the dipeptidyl peptidase-4 (DPP-4) enzyme. The molecular docking studies have revealed that compounds 22, 23, 29, and 30 showed hydrogen bonds with the DPP-4 enzyme while in-vitro tests have revealed that compound 30 has (IC50 values 12.82 nM), exhibited potent activity compared to the standard drug, sitagliptin (14.8 nM). Among the heterocyclic compounds, phthalimide and pyrazole derivatives were found more potent for DPP-4 inhibitors. © 2024 Wiley-VHCA AG, Zurich, Switzerland.
Docking Simulation and Anti-Inflammatory Profile of Some Synthesized Heterodimer of Pyrazole
(Pleiades journals, 2020) Pratima Yadav; Ranjeet Kumar; Ashish Kumar Tewari
Abstract: In the present studies, novel pyrazole derivatives have been synthesized linked through various linkers for the anti-inflammatory evaluation. The anti-inflammatory evaluation have been carried out by molecular docking and in vivo experimental models. The docking studies of these synthesized compounds have been performed with the active site of COX-2 compared to celecoxib and in vivo on carrageenan induced rat paw edema. Among all compounds (VIa and VIb) shown good anti-inflammatory activity. © 2020, Pleiades Publishing, Ltd.
Experimental and Theoretical Study for the Assessment of the Conformational Analysis of Pyrazolone Derivatives: Employing Quantitative Analysis for Intermolecular Interactions
(Wiley-Blackwell, 2017) Ranjeet Kumar; Praveen Singh; Simon Parsons; Ashish K. Tewari
Synthesis of four new flexible pyrazolone derivatives have been carried out for conformational studies. The conformational studies have been done with X-ray crystallography in solid state and theoretical calculation in gaseous state. The solid state study has revealed that substituted pyrazole moiety linked with pthalimido moiety via oxaethylene linker i. e. compounds 5 and 6 have shown folded conformation while increasing one methylene more in compound 7 has shown open conformation. However, theoretical calculation revealed that all compound stable in folded conformation. The quantitative analyses for intermolecular interaction of all compounds have been carried out by Hirshfeld surface analysis and Pixel calculations. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Experimental and Theoretical Study for the Assessment of the Conformational Stability of Polymethylene-Bridged Heteroaromatic Dimers: A Case of Unprecedented Folding
(American Chemical Society, 2016) Sunil K. Rai; Praveen Singh; Ranjeet Kumar; Ashish K. Tewari; Jiří Hostaš; Ramachandran Gnanasekaran; Pavel Hobza
This is the first report on the folding phenomenon of pyridazinone and triazinone dimers (1-5) bridged through an alkyl chain. Among them, direct evidence of conformational preference of 1, 2, and 5 was obtained through single crystal X-ray structures. However, prevalence of folded conformations was analyzed through theoretical investigation. © 2016 American Chemical Society.
Face-to-face stacking in sulfonamide based bis-ethylene bridged heteroaromatic dimers
(Royal Society of Chemistry, 2015) Ranjeet Kumar; Sunil K. Rai; Praveen Singh; Archana Gaurav; Pratima Yadav; Ranjana S. Khanna; Hariom Gupta; Ashish K. Tewari
Four sulfonamide based bis-ethylene bridged heteroaromatic dimers were synthesized for analysis of their structural and conformational properties. Interestingly, all models showed intramolecular offset face-to-face stacking between the tosyl group and heteroaromatic system in their solid state conformations. 1H NMR of the solutions revealed that the conformations were not far off from the solid state stacked geometry. However, gaseous state optimizations of different conformers divulged that the crystal structures were the lowest energy conformers. © The Royal Society of Chemistry 2015.
Identification of a HSP14-3-3 in Setaria cervi and its cross-reactivity with W bancrofti-infected human sera
(Blackwell Publishing Ltd, 2020) Faiyaz Ahmad; Ranjeet Kumar; Sarika Gupta; Sushma Rathaur
Aim: Identification of a 29 kDa heat stress protein in filarial parasite Setaria cervi and evaluation of its diagnostic potential against lymphatic filariasis. Methods and results: The Heat shock proteins (HSPs) were induced in filarial parasite S cervi by incubated at 42°C for 2 hours. The 10% SDS-PAGE of cytosolic extract showed several over-expressed bands. The MALDI-LC/MS analysis of 29 kDa band showed 100% similarity with Bm14-3-3 like protein 2. Multiple sequence alignment of Bm14-3-3 like protein 2 sequence with W bancrofti, Caenorhabditis elegans; Loa loa and Homo sapiens showed 100%, 86%, 83% and 78%, sequence similarity respectively. The antigenic efficacy of Sc14-3-3 protein was evaluated with different filarial sera using ELISA which showed cross-reactivity in order to Endemic Normal (EN) < Microfilaraemic (MF) < Chronic(CH) with IgG1 and EN < CH < MF in IgG4 ELISA. IgG1- and IgG4-specific immunoblotting with CH and MF sera further explicated its specific antigenic cross-reactivity. Conclusion: A 29 kDa heat shock protein of S cervi was identified as 14-3-3 protein having 100% homology to human filarial parasite B malayi. It showed strong reactivity with IgG1 and IgG4 subclass antibodies of W bancrofti-infected human sera suggesting that 14-3-3 protein could be used as a vaccine/ diagnostic marker. © 2020 John Wiley & Sons Ltd
Inhibition of Setaria cervi protein tyrosine phosphatases by Phenylarsine oxide: A proteomic and biochemical study
(Elsevier B.V., 2016) Neetu Singh; Mohit Wadhawan; Savitri Tiwari; Ranjeet Kumar; Sushma Rathaur
Phenylarsine oxide (PAO), a specific protein tyrosine phosphatase (PTP) inhibitor significantly decreased the motility and viability of Setaria cervi ultimately leading to its death. The PTP activity present in the cytosolic and detergent soluble fractions as well as on surface of these parasites was significantly inhibited by PAO. A marked alteration in protein spots abundance after proteomic analysis showed 14 down-regulated and 9 upregulated spots in the treated parasites as compared to the control. The PTP inhibition led to increase in the cytosolic and mitochondrial calpain activity in these parasites. PAO also blocked the ATP generation in the parasite depicted by reduced activity of phosphoglycerate kinase and expression of enolase. An increased ROS level, induced lipid peroxidation/protein carbonyl formation and decreased activity of different antioxidant enzymes like thioredoxin reductase, glutathione reductase and glutathione transferases was also observed in the PAO treated parasites. PAO, thus disturbs the overall homeostasis of the filarial parasite by inhibiting PTPs. Thereby suggesting that these molecules could be used as a good chemotherapeutic target for lymphatic filariasis. © 2016 Elsevier B.V.
Isolation of medicinally important constituents from rare and exotic medicinal plants
(Elsevier, 2018) Ranjeet Kumar; Ashish Kumar Tewari
Various exotic medicinal plants are found to exhibit anticancer, cell signaling, antiviral, antioxidant, antispasmodics, immunomodulatory, and antiinflammatory properties. The bioactive compounds such as flavanoids, alkaloids, steroids, terpenoids, and saponins as well as useful plant drugs including vinblastine, vincristine, taxol, podophyllotoxin, camptothecin, digitoxigenin, gitoxigenin, digoxigenin, tubocurarine, morphine, codeine, aspirin, atropine, pilocarpine, capscicine, allicin, curcumin, and artemesinin have been isolated from these plants. In this chapter, we have described some natural products, their synthesis, pharmaceutical details, and isolation, that is, extraction from Adonis vernalis, Aesculus hippocastanum, Fraxinus rhynchophylla, Atropa belladonna, Berberis vulgaris, Hydrastis Canadensis, and Taxus brevifolia plants. © 2018 Elsevier Ltd. All rights reserved.
Medicinal properties of marine plants
(Elsevier, 2018) Ranjeet Kumar; Ashish Kumar Tewari
Marine organism, animals, sponge, bacteria, actinobacteria, cyanobacteria, fungi, microalgae, seaweeds and mangroves are extremely important oceanic resources, that is, source of biologically active natural products. Marine natural products can be defined as biologically active products as secondary metabolites as well as enzymes, lipids, and heteropolysaccharides. Therefore, in this chapter, we deal with the bioactive application of some natural product, that is, isolated from marine natural resources such as Dysidea etheria, Laurencia obtuse, Aplidiopsis confluata, Tunicate didemnum sp., Nostoc linckia, and Lyngbya majuscule. Further, we also deal with the extraction and synthesis of these natural products © 2018 Elsevier Ltd. All rights reserved.
Miltefosine in children with visceral leishmaniasis
(2006) Utpal Kant Singh; Rajniti Prasad; Ranjeet Kumar; Bir Prasad Jaiswal
Sixty four children (38 boys and 26 girls), aged 1 yr to 14 yr, presenting with fever, splenomegaly and positive LD body in splenic smear examination, admitted to pediatric ward of Nalanda Medical college and Child care center between 1st July 03 to 30th June 04 were taken for study. Patients were categorized into two groups: 44 were in Group I (Patients who had not received prior anti-leishmanial drug) and 20 in Group II (Patients who had received 30 days course of SAG; 20 mg/kg/day). All patients were given Miltefosine in dose of 2.5 mg/kg /day od or bid per orally to a maximum of 100 mg and were followed at completion of therapy, 1 month and 6 months for clinical response, splenic size and parasite density. 63 patients had parasitological cure with relapse in one patient of Group I during follow up. One patient in Group II had no response with first course but became parasitologically negative with 2nd course of Miltefosine. In Group I, one patient had persistent splenomegaly and found to have associated portal hypertension. GI side effects i.e. diarrhea and vomiting were observed in 26 and 23 patients respectively. Majority of patients had pancytopenia. Elevated ALT (>3 times of normal) were seen in 28 and 11 patients of Group I and Group II respectively which returned to normal in subsequent follow up. The final cure rates were 93.2% and 95% in Groups I and II respectively.
Miltefosine: An Oral Drug for Visceral Leishmaniasis
(The Indian Journal of Pediatrics, 2004) Rajniti Prasad; Ranjeet Kumar; B.P. Jaiswal; Utpal Kant Singh
Miltefosine, a phosphocholine analogue originally developed as antimalignant drug, has been found to be highly active against leishmania in vitro and animal model. 1,2 Based on these experiences this drug was tried against human visceral leishmaniasis and found to be highly effective and achieved 97% and 94% cure in phase 2 and phase 3 trial in children.
Molecular cloning, purification and characterization of Brugia malayi phosphoglycerate kinase
(Academic Press Inc., 2017) Ranjeet Kumar; Pawan Kumar Doharey; Jitendra Kumar Saxena; Sushma Rathaur
Phosphoglycerate kinase (PGK) is a glycolytic enzyme present in many parasites. It has been reported as a candidate molecule for drug and vaccine developments. In the present study, a full-length cDNA encoding the Brugia malayi 3-phosphoglycerate kinase (BmPGK) with an open reading frame of 1.3 kb was isolated and PCR amplified and cloned. The exact size of the BmPGK's ORF is 1377 bps. The BmPGK gene was subcloned into pET-28a (+) expression vector, the expressed enzyme was purified by affinity column and characterized. The SDS–PAGE analysis revealed native molecular weight of recombinant Brugia malayi 3-phosphoglycerate kinase (rBmPGK) to be ∼45 kDa. The enzyme was found sensitive to temperature and pH, it showed maximum activity at 25 °C and pH 8.5. The Km values for PGA and ATP were 1.77 and 0.967 mM, respectively. The PGK inhibitor, clorsulon and antifilarial drugs albendazole and ivermectin inhibited the enzyme. The specific inhibitor of PGK, clorsulon, competitively inhibited enzyme with Ki value 1.88 μM. Albendazole also inhibited PGK competitively with Ki value 35.39 μM. Further these inhibitory studies were confirmed by docking and molecular simulation of drugs with enzyme. Clorsulon interacted with substrate binding site with glutamine 37 as well as in hinge regions with aspartic acid 385 and valine 387 at ADP binding site. On the other hand albendazole interacted with asparagine 335 residues. These effects were in good association with binding interactions. Thus current study might help in designing and synthesis of effective inhibitors for this novel drug target and understanding their mode of interaction with the potent anthelmintic drugs. © 2017 Elsevier Inc.
Oral atropine sulfate for infantile hypertrophic pyloric stenosis
(Springer, 2005) Utpal Kant Singh; Ranjeet Kumar; Rajniti Prasad
This study aimed to evaluate the effectiveness of oral atropine in the management of IHPS. Cases were diagnosed clinically and confirmed sonographically. Atropine was given orally from the outset at a dose of 0.18mg/kg/day in eight divided doses, increased daily by 1/4th of the commencing dose till vomiting ceased. Ultrasonographic evaluation of pyloric muscle thickness and length was done at the commencement of treatment, after completion of treatment and at 3,6,9,12 and 15 months follow up. Oral atropine was effective in 11/12 (91.06%) cases. Vomiting ceased in 14 to 21 days in all cases. One case required initial 7 days of I.V. treatment followed by 18 days oral treatment to stop vomiting. USG evidence of normalization of pylorus was observed in all these cases, 3-15 months after completion of treatment. We conclude that oral atropine proved to be a simple, effective, safe, very cheap and acceptable treatment option for IHPS.
Quantitative intermolecular interactions (Cl⋯Cl, Cl⋯F, and F⋯F) analysis of halogen substituted nicotinonitrile derivatives and in-silico anti-diabetic activity
(Elsevier B.V., 2025) Amit Jaiswal; Manima Mishra; Murli Dhar Mitra; Masoud Darvish Darvish Ganji; Vipin Kumar; Ashish Kumar Tewari; Ranjeet Kumar
Here, we have synthesized the nicotinonitrile derivatives (1–4) for studies of intermolecular non covalent halogen-halogen interactions such as Cl⋯Cl, Cl⋯F, and F⋯F. The X-ray crystallography studies have revealed that compounds 1–3 have shown Cl⋯F interaction. In contrast,e compound 2 has shown Cl⋯Cl interaction, and compound 4 has shown F⋯F interaction. Further, these intermolecular interactions have also been quantified by Hirshfeld surface analysis. Furthermore, we have also done in-silico anti-diabetic activity with PDB id 2OLE compared with ertugliflozin and sitagliptin (DPP-4) inhibitors, which are used to treat type II diabetes mellitus. © 2024 Elsevier B.V.