89 results on '"Singh, Parvesh"'
Search Results
2. Special Issue "Hybrid Drugs: Design and Applications".
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Singh, Parvesh and Kumar, Vipan
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DRUG design , *TUMOR suppressor proteins , *DRUG discovery , *ANTINEOPLASTIC agents , *CANCER cell growth - Abstract
These endeavours offer the prospect of discovering new drug candidates that could outperform existing anti-infective and anticancer medications in terms of safety and efficacy. The widely held belief in the potential superiority of agents capable of modulating multiple biological targets has led to the adoption of molecular hybridization as an effective technique in the realm of drug discovery and development. While significant strides have been taken in synthesizing potential hybrid anti-HIV drugs, it is pertinent to acknowledge that no such drug has yet progressed to the development stage or preclinical trials. [Extracted from the article]
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- 2023
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3. Synthesis, Structural Elucidation and Anti-Bacterial Evaluation of Fluorinated and Non-Fluorinated Schiff Bases of Quinazoline-4(3H)-One.
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Manhas, Neha, Singh, Parvesh, and Koorbanally, Neil A.
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SCHIFF bases , *THIOPHENES , *METHICILLIN-resistant staphylococcus aureus , *KLEBSIELLA pneumoniae , *MOLECULAR hybridization , *GRAM-negative bacteria , *LINEZOLID - Abstract
A relatively shorter procedure for the synthesis of 3-amino-2-methyl-3H-quinazolin-4-one (4) was developed. The subsequent condensation reaction of 4 with a variety of aldehydes afforded several novel Schiff bases (5a-r) counting its molecular hybridization with the indole, thiophene, and quinoline pharmacophoric units. Full structural elucidation of all Schiff bases was conducted with the help of 1H and 13C NMR coupled with two-dimensional (HMBC, HSQC and COSY) techniques, and provides a reference point for the structural characterization of all the future synthesized scaffolds with a similar core structure. Furthermore, the antibacterial screening of all Schiff bases was undertaken using four Gram-negative strains, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumonia and Salmonella typhimurium, and two Gram positive-strains, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus (MRSA). In general, several compounds showed activity against MRSA. [ABSTRACT FROM AUTHOR]
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- 2022
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4. Solvent-free mechanochemical synthesis of bisthioglycolic acid derivatives: an efficient and versatile strategy for carbon–sulfur bond formation.
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Naikoo, Rayees Ahmad, Singh, Parvesh, Kumar, Rupesh, and Bhargava, Gaurav
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THIOGLYCOLIC acid , *COST effectiveness - Abstract
An eco-friendly, easily achievable and efficient strategy has been explored to synthesize functionalized bisthioglycolic acids using a variety of aldehydes and thioglycolic acid. The employed protocol is solvent free and provides the desirable products in excellent yields (90–99%) with atom economy. Besides, cost effectiveness, short reaction times and milder reaction conditions are among other captivating benefits of the reported methodology. [ABSTRACT FROM AUTHOR]
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- 2022
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5. Synthesis, antibacterial screening and computational studies of quinazoline-4 (3H)-one-triazole conjugates.
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Manhas, Neha, Singh, Parvesh, Singh-Pillay, Ashona, and Koorbanally, Neil
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KLEBSIELLA pneumoniae , *DNA topoisomerase II , *ANTIBACTERIAL agents , *QUINAZOLINE , *GRAM-negative bacteria , *CIPROFLOXACIN - Abstract
• Full structure elucidation of all compounds using 2D-NMR (HMBC, HSQC, COSY) techniques and other spectral evidence. • Antibacterial screening of compounds against both gram-positive and gram-negative strains. • Most active conjugate exhibited superior activity to ampicillin against klebsiella pneumoniae. • Target identification using pharmacophore modelling and docking simulations. A novel series of quinazoline-4 (3H)-one-tagged triazole conjugates were synthesised using the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) methodology. All synthesized compounds were structurally elucidated with the help of 2D-NMR (HMBC, HSQC, COSY) techniques and other spectral evidence. The in vitro antibacterial activities of these compounds were evaluated and compared with commercial drugs ciprofloxacin, ampicillin, and levofloxacin. Four compounds (4a, 4d , 4g , and 4i) of the series exhibited potent activity and selectivity against the gram-negative bacterial strains. Amongst these, 4i emerged as the most active conjugate with almost 12-fold superior activity to ampicillin against Klebsiella pneumoniae (gram-negative), one of the most challenging multidrug-resistant strains worldwide. Structure-activity relationship (SAR) analysis further revealed that the incorporation of a triazole ring incredibly increased the antibacterial activity of quinazoline Schiff bases towards the gram-negative bacteria. Moreover, the para -positioning of strong electron-donating (–OCH 3) and electron-withdrawing (-NO 2) groups at the phenyl ring of the triazole ring positively influenced the antibacterial activity, whereas the meta -substitution generally decreased the antibacterial activity of the conjugates. Furthermore, molecular docking studies were conducted to explore the binding characteristics of these compounds in the binding site of DNA gyrase (Staphylocouccus aureus). [ABSTRACT FROM AUTHOR]
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- 2023
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6. Synthesis, photostability and antibacterial activity of a series of symmetrical α,β-unsaturated ketones as potential UV filters.
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Magaji, Buhari, Singh, Parvesh, Skelton, Adam A., and Martincigh, Bice S.
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PROTOGENIC solvents , *ANTIBACTERIAL agents , *APROTIC solvents , *POLAR solvents , *KETONES , *OXAZOLIDINONES - Abstract
An improved Knoevenagel condensation yielded three α,β-unsaturated ketones whose photostability and antibacterial properties were evaluated. [Display omitted] • Three dibenzylideneacetones were synthesized by an improved Knoevenagel reaction. • Compound 2 with -N(CH 3) 2 groups exhibits potential as a broad-spectrum UV filter. • Compounds 2 & 3 show good antibacterial activity and are leads for new antibiotics. A series of three symmetrical α,β-unsaturated ketones, namely, (1 E ,4 E)-1,5-bis[4-(methylthio)phenyl]penta-1,4-dien-3-one, 1 , (1 E ,4 E)-1,5-bis[4-(dimethylamino)phenyl]penta-1,4-dien-3-one, 2 , and (1 E ,4 E)-1,5-bis[4-(ethyl)phenyl] penta-1,4-dien-3-one, 3 , were synthesized in excellent yields (above 70%) and within a short reaction time (1 h), via an improved Knoevenagel condensation with acetyl acetone and substituted benzaldehydes. All the compounds were fully characterized by UV/Vis, IR, NMR and mass spectrometry. In addition, compound 1 was characterized by single crystal X-ray diffraction. The photostability of the prepared compounds was investigated in solvents of different polarity and proticity by exposure to simulated solar radiation. Three solvents were used, namely, ethyl acetate, dimethylsulfoxide and methanol. The change in UV absorption was monitored by a standard spectrophotometric method and photodegradation products were identified by 1H NMR. According to the results, 1 and 3 were not photostable, and suffered significant changes in their UV absorption spectra. Compound 2, on the other hand, was observed to be considerably photostable in the polar protic solvent methanol but less photostable in the polar aprotic solvent dimethylsulfoxide. All three compounds (1 – 3) photodegraded appreciably in the less polar aprotic solvent ethyl acetate. Therefore, their photostability is solvent dependent. The antibacterial activity of 1 – 3 was evaluated by means of the modified broth microdilution method against both gram-negative and gram-positive bacterial strains. Compounds 2 (methylated amine) and 3 (ethyl) have electron-releasing substituents and they were found to have excellent activity against all the tested bacteria. Thus, compounds 2 and 3 can be further explored as potential leads for the development of cheaper, safer, more effective and potent antibiotics against both gram-positive and gram-negative bacterial strains, and compound 2 is a good candidate for use in sunscreen formulations if dissolved in a polar solvent. [ABSTRACT FROM AUTHOR]
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- 2023
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7. Synthesis of chloro, fluoro, and nitro derivatives of 7‐amino‐5‐aryl‐6‐cyano‐5H‐pyrano pyrimidin‐2,4‐diones using organic catalysts and their antimicrobial and anticancer activities.
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Aremu, Oluwole S., Singh, Parvesh, Singh, Moganavelli, Mocktar, Chunderika, and Koorbanally, Neil A.
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CATALYSTS , *NUCLEAR magnetic resonance spectroscopy , *HELA cells , *STAPHYLOCOCCUS aureus , *ESCHERICHIA coli , *AROMATIC aldehydes , *OXACILLIN - Abstract
Chloro, fluoro, and nitro derivatives of 7‐amino‐5‐aryl‐6‐cyano‐5H‐pyrano pyrimidin‐2,4‐diones were produced by reacting malononitrile, barbituric acid, and aromatic aldehydes together with a DABCO catalyst in an aqueous one‐pot reaction. This is the first report of these compounds being synthesized with DABCO as a catalyst, which produced the compounds in yields in excess of 90%. The 2,4‐difluoro derivative (11) was novel. The structures of the synthesized compounds were elucidated by means of 1H, 13C, and 2D NMR spectroscopy. Compound 2 (2‐Cl derivative) had MBC values of <200μM against both Staphylococcus aureus and MRSA, and the 2‐nitro derivative 5 had an MBC of 191μM against the Gram–ve Escherichia coli. The synthesized compounds were also tested for their anticancer activity against a HeLa cell line, where all the compounds showed better activity (IC50 values between 129μM and 340μM) than 5‐fluorouracil, a commonly known anticancer drug. [ABSTRACT FROM AUTHOR]
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- 2019
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8. Recent advances (2015–2016) in anticancer hybrids.
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Kerru, Nagaraju, Singh, Parvesh, Koorbanally, Neil, Raj, Raghu, and Kumar, Vipan
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ANTINEOPLASTIC agents , *DRUG development , *CAUSES of death , *MULTIDRUG resistance , *STRUCTURE-activity relationships , *BIOCHEMICAL mechanism of action - Abstract
In spite of the development of a large number of novel anticancer drugs over the years, Cancer remains as a prominent cause of death, worldwide. Numerous drugs that are currently in clinical practice have developed multidrug resistance along with fatal side effects. Therefore, the utilization of single-target therapy is incapable of providing an effective control on the malignant process. Molecular hybridization, involving a combination of two or more pharmacophores of bioactive scaffolds to generate a single molecular architecture with improved affinity and activity, in comparison to their parent molecules, has emerged as a promising strategy in recent drug discovery research. Hybrid anticancer drugs are of great therapeutic interests since they can potentially overcome most of the pharmacokinetic drawbacks encountered with conventional anticancer drugs. Strategically, the design of anticancer drugs involved the blending or linking of an anticancer drug with another anticancer drug or a carrier molecule which can efficiently target cancer cells with improved biological potential. Major advantages of hybrid anticancer drugs involved increased specificity, better patient compliance, and lower side effects along with reduction in chemo-resistance. The successful utilization of this technique in design and synthesis of novel anticancer hybrids has been well illustrated and documented in the literature. The purpose of the present review article will be to provide an emphasis on the recent developments (2015–16) in anticancer hybrids with insights into their structure-activity relationship (SAR) and mechanism of action. [ABSTRACT FROM AUTHOR]
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- 2017
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9. A combined TD-DFT and spectroscopic investigation of the solute–solvent interactions of efavirenz.
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Jordaan, Maryam A., Singh, Parvesh, and Martincigh, Bice S.
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AIDS treatment , *ANTIRETROVIRAL agents , *CYCLOHEXANE , *DENSITY functional theory , *MOLECULAR spectroscopy , *ULTRAVIOLET-visible spectroscopy - Abstract
Efavirenz, commercially known as Sustiva® or Stocrin®, is a first-line antiretroviral treatment for HIV/AIDS. The clinical efficacy of efavirenz is, however, hindered by its solubility. We sought to investigate the solute–solvent effects of efavirenz by means of a combined qualitative study implementing UV–visible spectrophotometry, 1 H NMR spectroscopy and time-dependent density functional theory (TD-DFT) calculations. The UV spectrum displayed two main absorbance maxima, band I and band II at 246–260 and 291–295 nm, respectively. A general bathochromic shift was noticed from the non-polar solvent cyclohexane to the most polar solvent DMSO (≈ 13.69 nm) in band I and a smaller bathochromic (≈ 2.17 nm) and hyperchromic shift was observed in band II. We propose that these observations are due to the role of the amino (NH) and carbonyl (CO) functionalities which induce charge-transfer and intra- and inter-molecular hydrogen bonding. The aromatic and amine protons showed the most deshielded effects in the observed chemical shifts (δ) in the more polar DMSO- d 6 solvent relative to CDCl 3 . The 1 H NMR chemical shifts observed are due to the increased delocalization of the lone pair electrons of the amino nitrogen with increased polarity of the more polar DMSO solvent. The theoretical reproduction of the UV and 1 H NMR spectra by means of TD-DFT is in good agreement with the experimental results. [ABSTRACT FROM AUTHOR]
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- 2016
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10. Recent developments in biological activities of chalcones: A mini review.
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Singh, Parvesh, Anand, Amit, and Kumar, Vipan
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CHALCONES , *BIOACTIVE compounds , *DRUG development , *DRUG efficacy , *CANCER treatment , *TREATMENT of diabetes , *TUBERCULOSIS treatment - Abstract
Chalcones represent key structural motif in the plethora of biologically active molecules including synthetic and natural products. Synthetic manipulations of chalcones or their isolation from natural sources are being investigated worldwide for the development of more potent and efficient drugs for the treatment of several dreadful diseases such as cancer, diabetes, HIV, tuberculosis, malaria etc. Over the past few years, a large volume of research papers and review articles highlighting the significance of chalcone derivatives has been compiled in the literature. The present review article focuses on the recent developments (2010–2014) on various pharmacological and medicinal aspects of chalcones and their analogues. [ABSTRACT FROM AUTHOR]
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- 2014
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11. β-Lactam-Synthon-Interceded Synthesis of Isatin-Imidazolidine--thione Conjugates with Structural Validation using Molecular Dynamic Simulations and Cytotoxic Evaluation.
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Nisha, Singh, Parvesh, Hendricks, Denver T., Bisetty, Krishna, and Kumar, Vipan
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LACTAMS , *ISATIN , *IMIDAZOLIDINES , *INTERMOLECULAR interactions , *ISOTHIOCYANATES , *MOLECULAR dynamics , *CELL-mediated cytotoxicity - Abstract
β-Lactam-synthon-interceded synthesis of isatin-imidazolidine- 2-thione conjugates was carried out via base-assisted intermolecular amidolysis of 3-isothiocyanato-2-azetidinones with C-5 substituted isatins. The observed enolization in the assigned structure of the conjugates was validated using molecular dynamic (MD) simulations performed under explicit solvent conditions. The synthesized scaffolds were also evaluated for their cytotoxic profiles against the oesophageal cancer cell line WHCO1. [ABSTRACT FROM AUTHOR]
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- 2013
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12. A Molecular Dynamics Study of Lunasin.
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Singh, Parvesh and Bisetty, Krishna
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AMINO acids , *PEPTIDES , *MAMMALIAN cell cycle , *CARCINOGENESIS , *MOLECULAR dynamics - Abstract
Lunasin, a 43 amino acid peptide, suppresses chemically induced transformations in mammalian cells and skin carcinogenesis in mice. This peptide has also been reported to exhibit very good bioavailability after its oral administration. However, despite its biological and medicinal significance, the exact three-dimensional (3D) structure of lunasinis thus far not yet fully characterized. Thus this work is aimed at exploring the conformational profile of lunasin,using classical molecular dynamics (MD) simulations at the time scale of 300 ns. The results obtained from the MD trajectory reveal that lunasin has a strong propensity to exhibit three characteristic helical bundles in its structure supported by residues His5 -Cys10, Cys22 -Ile30 and Asp35 -Asp41. The reported cell adhesion motif (Arg-Gly-Asp) of lunasin responsible for its binding to cell chromatin, on other hand, did not exhibit any characteristic secondary feature. The structural information obtained from the current study could be useful to better understand the bioactive conformation of lunasin. [ABSTRACT FROM AUTHOR]
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- 2012
13. Synthesis, docking and in vitro antimalarial evaluation of bifunctional hybrids derived from β-lactams and 7-chloroquinoline using click chemistry
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Singh, Pardeep, Singh, Parvesh, Kumar, Malkeet, Gut, Jiri, Rosenthal, Philip J., Kumar, Kewal, Kumar, Vipan, Mahajan, Mohinder P., and Bisetty, Krishna
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ANTIMALARIALS , *LACTAMS , *QUINOLINE , *PLASMODIUM falciparum , *TETRAHYDROFOLATE dehydrogenase , *RING formation (Chemistry) - Abstract
Abstract: 1,2,3-Triazole tethered β-lactam and 7-chloroquinoline bifunctional hybrids were synthesized and evaluated as potential antimalarial agents. Activity against cultured Plasmodium falciparum was dependent on the N-substituent of the β-lactam ring as well as the presence of bis-triazole at the C-3 position. The observed activity profiles were further substantiated by docking studies via inhibition of P. falciparum dihydrofolate reductase (PfDHFR), a potential target for the development of new anti-malarials. [Copyright &y& Elsevier]
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- 2012
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14. Preparation, Spectrochemical, and Computational Analysis of L-Carnosine (2-[(3-Aminopropanoyl)amino]-3-(1H-imidazol-5-yl)propanoic Acid) and Its Ruthenium (II) Coordination Complexes in Aqueous Solution.
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Branham, Michael Lee, Singh, Parvesh, Bisetty, Krishna, Sabela, Myalo, and Govender, Thirumala
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ANALYTICAL chemistry , *CHEMICAL reactions , *MOLECULAR structure , *CHEMICAL structure , *DENSITY functionals , *RUTHENIUM compounds - Abstract
This study reports the synthesis and characterization of novel ruthenium (II) complexes with the polydentate dipeptide, L-carnosine (2-[(3-aminopropanoyl)amino]-3- (1H-imidazol-5-yl)propanoic acid). Mixed-ligand complexes with the general composition [MLp(Cl)q(H2O)r]·xH2O (M = Ru(II); L = L-carnosine; p = 3 - q; r = 0-1; and x = 1-3) were prepared by refluxing aqueous solutions of the ligand with equimolar amounts of ruthenium chloride (black-alpha form) at 60 °C for 36 h. Physical properties of the complexes were characterized by elemental analysis, DSC/TGA, and cyclic voltammetry. The molecular structures of the complexes were elucidated using UV-Vis, ATR-IR, and heteronuclear NMR spectroscopy, then confirmed by density function theory (DFT) calculations at the B3LYP/LANL2DZ level. Two-dimensional NMR experiments (¹H COSY, 13C gHMBC, and 15N gHMBC) were also conducted for the assignment of chemical shifts and calculation of relative coordination-induced shifts (RCIS) by the complex formed. According to our results, the most probable coordination geometries of ruthenium in these compounds involve nitrogen (N1) from the imidazole ring and an oxygen atom from the carboxylic acid group of the ligand as donor atoms. Additional thermogravimetric and electrochemical data suggest that while the tetrahedral-monomer or octahedral-dimer are both possible structures of the formed complexes, the metal in either structure occurs in the (2+) oxidation state. Resulting RCIS values indicate that the amidecarbonyl, and the amino-terminus of the dipeptide are not involved in chelation and these observations correlate well with theoretical shift predictions by DFT. [ABSTRACT FROM AUTHOR]
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- 2011
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15. Computer Simulation Studies of Trishomocubane Heptapeptide of the Type Ac-Ala3-Tris-Ala3-NHMe.
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Singh, Parvesh, Bisetty, Krishna, Govender, Penny, and Kruger, Gert
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PEPTIDE analysis , *CUBANE derivatives , *MOLECULAR dynamics , *GABA agonists , *POLYPEPTIDES - Abstract
As part of an extension on the cage peptide chemistry, the present work involves an assessment of the conformational profile of trishomocubane heptapeptide of the type Ac-Ala3-Tris-Ala3-NHMe using molecular dynamics (MD) simulations. All MD protocols were explored within the framework of a molecular mechanics approach using the PARM94 force field parameters modified in-house to mimic the implicit and explicit solvent conditions. The 50 ns MD trajectories revealed a tendency of the trishomocubane polypeptide to adopt bent conformations in vacuo, MEOH and TIP3P solvent models, consistent with previous studies undertaken in our laboratory. The aim of this paper is to exemplify the tendency of the highly constrained cage residues to promote reverse-turn characteristics in the polypeptide chains, which could play a pivotal role in the design of new cage peptidomimetics. [ABSTRACT FROM AUTHOR]
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- 2011
16. Synthesis and docking studies of thiophene scaffolds in COX-2.
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Singh, Parvesh, Sharma, Parul, Bisetty, Krishna, and Mahajan, Mohinder P.
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THIOPHENES , *CHEMICAL synthesis , *CARBON monoxide , *CHEMICAL reactions , *THIONES , *KETONES , *RING formation (Chemistry) - Abstract
A series of new thiophene compounds 6a-6l was synthesized from the reactions of in situ generated cross-conjugated enaminothiones 2 and a-bromoketones/ethyl bromoacetate. Moreover, the synthesis of 1,3-thiazine 12 and functionalized thiopyran 18 heterocycles from the cycloaddition reactions of N,N'-bis[(dimethylamino)methylene]thiourea 9, is also described. Additionally, the binding conformations of these compounds 6a-6l and some anti-inflammatory drugs (NSAIDs) were determined by their docking in the active site of the Cyclooxygenase-2 (COX-2) enzyme. [ABSTRACT FROM AUTHOR]
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- 2011
17. Conformational profile of bombesin assessed using different computational protocols
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Sharma, Parul, Singh, Parvesh, Bisetty, Krishna, Corcho, Francesc J., and Perez, Juan. J.
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BOMBESIN , *PROTEIN conformation , *MOLECULAR dynamics , *PEPTIDES , *METHODOLOGY , *COMPUTATIONAL biology , *NUCLEAR magnetic resonance - Abstract
Abstract: The present work involves the study of the conformational profile of bombesin using different computational procedures used to explore the configurational space based on molecular dynamics simulations. Specifically, the present study describes the effect of using Berendsen''s versus Langevin''s thermostat and on the other hand, the use of the multicanonical replica exchange molecular dynamics as compared to standard molecular dynamics. In these simulations the solvent was modeled using the Onufriev, Bashford and Case implementation of Generalized Born procedure. The detailed computational analysis agrees well with the aggregated information previously reported in the NMR study of the peptide in a mixture of trifluoroethanol/water. Present results show a clear preference for the peptide to attain a helical structure on the segment 6–14, with a tendency to adopt a α-helix at the C-terminus aligning the aromatic residues Trp8 and His12 together with Gln7, known to be important for peptide mediated activation. Finally, the three methodologies used in the present work yield similar structural results, although a detailed analysis reveals biases that need to be considered when performing this kind of studies. [Copyright &y& Elsevier]
- Published
- 2010
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18. Molecular dynamics simulations of Ac-3Aib-Cage-3Aib-NHMe.
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Singh, Parvesh, Sharma, Parul, Bisetty, Krishna, and Perez, Juan J.
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MOLECULAR dynamics , *SIMULATION methods & models , *SOLVENTS , *CONFORMATIONAL analysis , *DIMETHYL sulfoxide , *WATER , *MOLECULAR structure , *POLYPEPTIDES - Abstract
Solvents play a stabilising role with the more stable conformations obtained in polar solvents than in vacuo. We investigate to what extent the structural propensities of the pentacyclo-undecane (PCU) cage polypeptide chain of the type Ac-3Aib-Cage-3Aib-NHMe are influenced in implicit water and in explicit solvents: methanol (MEOH), dimethyl sulphoxide (DMSO) and TIP3P water. The sampling of the α-helical conformations of the PCU cage polypeptide was investigated using the in-house modified PARM94 force-field parameters. Analysis of 50 ns molecular dynamics (MD) simulations revealed a tendency of the PCU cage polypeptide to assume bent structures, especially in polar solvents. The choice of solvents was designed to relate the simulations to physiological conditions. The individual amino-isobutyric acid residues predominantly sampled the right-handed and left-handed 310-helical conformations, indicating that the helical conformations are preferred in all four environments (in vacuo, MEOH, water and DMSO). Additionally, the 100 ns replica exchange MD (REMD) simulations of the PCU cage polypeptide in implicit water revealed more conformational variety present than in explicit solvents, and is more consistent with previous theoretical studies on the PCU cage residue. The present theoretical results may help in rationalising experimental results on these PCU cage polypeptides, and definitely show the importance of a dynamical approach for a correct interpretation and prediction of the conformational behaviour of the PCU cage molecules in different environments. [ABSTRACT FROM AUTHOR]
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- 2010
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19. Cycloaddition reactions of cross-conjugated enaminones
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Singh, Parvesh, Sharma, Parul, Bisetty, Krishna, and Mahajan, Mohinder P.
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RING formation (Chemistry) , *ENAMINES , *CARBOXYLIC acids , *ETHANES , *KETENES , *PYRAN , *MOLECULAR dynamics , *SIMULATION methods & models - Abstract
Abstract: A detailed study on the cycloaddition reactions of cross-conjugated enaminones 1 and 9 with dimethyl acetylenedicarboxylate (DMAD) and ketenes is described. The reactions provide a variety of pyran (4, 11), pyran-2-one 14 and pyrrol-3-ylidene 8 derivatives having great pharmacological and medicinal significance. Moreover, the preferred formation of product 8 over 7 has been explained on the basis of molecular dynamics (MD) simulations performed on the intermediate 5 in the gas phase. The synthetic potential of enaminones 9 has further been explored by treating them with Lawesson''s reagent (LR) and trapping the in situ generated enaminothiones 16 with some acrylates 17 leading to the formation of thiopyran derivatives 19. To the best of our knowledge, this is the first report in which cross-conjugated enaminothiones 16 have been utilized in cycloaddition reactions. [Copyright &y& Elsevier]
- Published
- 2009
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20. Computational and Experimental Studies on the Hetero-Diels-Alder Reactions of Cross-conjugated Enaminones with Sulphene.
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Singh, Parvesh, Bisetty, Krishna, and Mahajan, Mohinder P.
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DIELS-Alder reaction , *ENAMINES , *DENSITY functionals , *SOLVENTS , *ORGANIC synthesis , *CHEMICAL reactions - Abstract
Ab initio and density functional theory (DFT) calculations have been used to investigate the feasibility of cycloaddition reactions of enaminones 1 with sulphene. Specifically, the geometry optimizations, frequency calculations and self-consistent reaction-field (SCRF) solvent simulations in combination with higher-quality relative energies carried out at the DFT level using the 6-31+G(d) basis set suggests that the product obtained is both thermodynamically and kinetically preferred, indicating the feasibility of this reaction. Additionally, experimental studies carried out on the reactions of these enaminones 1 with sulphene were also found to be in agreement with the theoretical predictions resulting in the synthesis of a variety of novel oxathiine derivatives having great biological and medicinal importance. [ABSTRACT FROM AUTHOR]
- Published
- 2009
21. Tandem [2+2] cycloaddition and Cope rearrangement in reactions of cross-conjugated azatrienes with conjugated ketenes: a facile single step synthesis of novel azocinone derivatives
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Singh, Parvesh, Bhargava, Gaurav, and Mahajan, Mohinder P.
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RING formation (Chemistry) , *CHEMICAL reactions , *KETENES , *OXO compounds - Abstract
Abstract: A facile single step synthesis of novel azocinone derivatives involving tandem [2+2] cycloaddition and Cope rearrangement in the reactions of cross-conjugated azatrienes with vinyl/isopropenyl ketenes supported by theoretical calculations is reported. [Copyright &y& Elsevier]
- Published
- 2006
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22. An in-depth analysis of the effect of substituents on imines in cycloaddition reactions with nitrosoalkenes
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Marwaha, Alka, Singh, Parvesh, and Mahajan, Mohinder P.
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IMINES , *ORGANONITROGEN compounds , *IMINO compounds , *POLYAMINES - Abstract
Abstract: An in-depth experimental and theoretical analysis of the reactions of simple acyclic imines with nitrosoalkenes is reported. The effect of the substituents on nitrogen as well as carbon atom of imines on the cycloaddition pathways followed is systematically explored. The reactions of various functionalized imines with nitrosoalkenes leading to the formation of imidazoles and imidazole-N-oxides have also been explored. The plausible mechanisms leading to various heterocycles have been proposed. [Copyright &y& Elsevier]
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- 2006
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23. Comparative reactivity of N′-(5-benzoyl/ethoxycarbonyl)thiazol-2-yl-N,N-dimethylformamidines with ketenes
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Singh, Parvesh, Marwaha, Alka, Singh, Harmeet, and Mahajan, Mohinder P.
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ELECTRONICS , *ORGANONITROGEN compounds , *SOLVENTS , *CHEMICAL reactions - Abstract
Abstract: The comparative account of the reactivities of N′-[(5-benzoyl and ethoxycarbonyl)thiazol-2-yl]-N,N-dimethylformamidines ( 1a and 1b ), tremendously influenced by the electronic nature of the substituents on C-5 of the thiazolic ring with various monosubstituted and conjugated ketenes is reported herein. The DA cycloadditions of the dienyl pyrimidinone 3h with both symmetrical as well as unsymmetrical dienophiles leading to the formation of various thiazolic pyrimidinone derivatives are also reported. [Copyright &y& Elsevier]
- Published
- 2005
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24. Facile synthesis and regioselective thio-Claisen rearrangements of 5-prop-2-ynyl/enyl-sulfanyl pyrimidinones: transformation to thienopyrimidinones
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Mohan, Chander, Singh, Parvesh, and Mahajan, M.P.
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KETENES , *OXO compounds , *CHEMICAL reactions , *PHYSICAL & theoretical chemistry - Abstract
Abstract: A successful generation and utilization of prop-2-ynyl/enyl-sulfanyl ketene in the synthesis of previously unknown pyrimidinones and their thio-Claisen rearrangements leading to thienopyrimidinones is described. [Copyright &y& Elsevier]
- Published
- 2005
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25. Synthesis of novel heterocyclic fused 1,3-diazabuta-1,3-dienes and accompanying rearrangements in their cycloaddition reactions with ketenes: synthesis of heterocyclic fused pyrimidinone derivatives
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Jayakumar, S., Singh, Parvesh, and Mahajan, Mohinder P.
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RING formation (Chemistry) , *PHENOLS , *KETENES , *PYRIMIDINES - Abstract
The reactions of 1,3-diazabuta-1,3-dienes 1 with 2-aminothiophenol have been shown to result in excellent yields of N-benzothiazol-2-yl-N′-aryl benzamidines 2. Their regioselective [4+2] cycloadditions with various ketenes are shown to yield novel benzothiazolo pyrimidinones 4. A similar and convenient protocol for the synthesis of bisthiosubstituted 1,3-diazabuta-1,3-dienes 8 and 9 and interesting rearrangements accompanying their [4+2] cycloadditions with a number of ketenes are described. [Copyright &y& Elsevier]
- Published
- 2004
- Full Text
- View/download PDF
26. β-Lactam-Synthon-Interceded Facile Synthesis of Functionally Decorated Thiohydantoins.
- Author
-
Mehra, Vishu, Singh, Parvesh, Manhas, Neha, and Kumar, Vipan
- Subjects
- *
LACTAMS , *INTRAMOLECULAR catalysis , *HYDANTOIN , *HETEROCYCLIC compounds , *CHEMICAL synthesis , *ISOTHIOCYANATES - Abstract
Base-promoted facile synthesis of thiohydantoins has been described via intramolecular amidolysis of C-3 functionalized 2-azetidinones. This approach provides a convenient and rapid access to diversely functionalized thiohydantoins compared to conventional protocols. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
27. An efficient unprecedented synthesis of novel functionalized imidazoles from secondary amino-N-carbothioic acid (phenyl-p-tolylimino-methyl)amides and dimethyl acetylenedicarboxylate
- Author
-
Marwaha, Alka, Singh, Parvesh, Mahajan, Mohinder P., and Velumurugan, D.
- Published
- 2004
- Full Text
- View/download PDF
28. Synthesis,Antidiabetic and Antitubercular Evaluation of Quinoline–pyrazolopyrimidine hybrids and Quinoline‐4‐Arylamines.
- Author
-
Cele, Nosipho, Awolade, Paul, Seboletswe, Pule, Khubone, Lungisani, Olofinsan, Kolawole, Islam, Md. Shahidul, Jordaan, Audrey, Warner, Digby F., and Singh, Parvesh
- Abstract
Two libraries of quinoline‐based hybrids 1‐(7‐chloroquinolin‐4‐yl)‐1
H ‐pyrazolo[3,4–d ]pyrimidin‐4‐amine and 7‐chloro‐N ‐phenylquinolin‐4‐amine were synthesized and evaluated for their α‐glucosidase inhibitory and antioxidant properties. Compounds with 4‐methylpiperidine andpara ‐trifluoromethoxy groups, respectively, showed the most promising α‐glucosidase inhibition activity with IC50=46.70 and 40.84 μM, compared to the reference inhibitor, acarbose (IC50=51.73 μM). Structure‐activity relationship analysis suggested that the cyclic secondary amine pendants andpara ‐phenyl substituents account for the variable enzyme inhibition. Antioxidant profiling further revealed that compounds with anN ‐methylpiperazine andN ‐ethylpiperazine ring, respectively, have good DPPH scavenging abilities with IC50=0.18, 0.58 and 0.93 mM, as compared to ascorbic acid (IC50=0.05 mM), while the best DPPH scavenger is NO2‐substituted compound (IC50=0.08 mM). Also, compound withN ‐(2‐hydroxyethyl)piperazine moiety emerged as the best NO radical scavenger with IC50=0.28 mM. Molecular docking studies showed that the present compounds are orthosteric inhibitors with their quinoline, pyrimidine, and 4‐amino units as crucial pharmacophores furnishing α‐glucosidase binding at the catalytic site. Taken together, these compounds exhibit dual potentials;i. e ., potent α‐glucosidase inhibitors and excellent free radical scavengers. Hence, they may serve as structural templates in the search for agents to manage Type 2 diabetes mellitus. Finally, in preliminary assays investigating the anti‐tubercular potential of these compounds, two pyrazolopyrimidine series compounds and a 7‐chloro‐N ‐phenylquinolin‐4‐amine hybrid showed sub‐10 μM whole‐cell activities againstMycobacterium tuberculosis . [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
29. An eco‐friendly, sustainable, and greener approach to the synthesis of Dihydroquinazolin‐4(1H)‐ones using a deep eutectic solvent.
- Author
-
Kumar, Gobind, Seboletswe, Pule, Manhas, Neha, Singh, Parvesh, Bhargava, Gaurav, Rajput, Jaspreet Kaur, and Kumar, Rupesh
- Abstract
A safer, greener, and more effective reaction methodology for the synthesis of dihydroquinazolinones (DHQs) has been developed. The deep eutectic solvent (DES) ZnCl2/urea employed in this study efficiently accelerated the cyclization of 2‐aminobenzamide with different aldehydes (aromatic and heteroaromatic) to afford the target scaffolds without the generation of any oxidized product. This method has exhibited remarkable advantages such as quick reaction time, mild reaction conditions, high yield (82%–98%), operational simplicity, and selectivity. The approach was observed to be tolerant to electron‐donating and electron‐withdrawing functional groups. Green metric parameters (AEf, OE, AE, RME, CE, etc.) determined further aided this greener chemical approach. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
30. Crystal structure of (E)-3-(benzylideneamino)-2-phenylthiazolidin-4-one, C16H14N2OS.
- Author
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Seboletswe, Pule, Zamisa, Sizwe J., Kumar, Gobind, and Singh, Parvesh
- Subjects
- *
CRYSTAL structure - Abstract
C16H14N2OS, monoclinic, P21/n (no. 14), a = 13.8369(4) Å, b = 15.8967(4) Å, c = 13.8600(4) Å, β = 109.983(1)°, V = 2865.11(14) Å3, Z = 8, Rgt(F) = 0.0439, wRref(F2) = 0.1091, T = 296.15 K. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
31. 7-Endo-trig Pictet–Spengler type cyclization of 5-alkylidene/arylidene-amino-3H-pyrimidin-4-ones: An efficient and diastereoselective synthesis of pyrimido[4,5-b] [1,4]benzodiazepines.
- Author
-
Naikoo, Rayees Ahmad, Kumar, Rupesh, Singh, Parvesh, and Bhargava, Gaurav
- Subjects
- *
BENZODIAZEPINES , *RING formation (Chemistry) , *SULFONIC acids - Abstract
The manuscript describes an efficient, atom economical synthesis of pyrimido[4,5-b][1,4]benzodiazepin-4-ones by relatively unexplored 7-endo-trig Pictet–Spengler type cyclisations. The synthetic methdodlogy involves the synthesis of different variants of 5-arylidene-amino-3H-pyrimidines and their p-toluene sulfonic acid mediated 7-endo-trig Pictet–Spengler type cyclisations to afford biologically relavent functionalized benzodiazepine condensed pyrimidinones such as pyrimido[4,5-b][1,4]benzodiazepines in good to excellent yields (82–94%). [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
32. Novel immobilization techniques of Acinetobacter (V2) and Paenibacillus (D9) bacterial strains for waste oil degradation.
- Author
-
Jeon, Yashmika, Bissessur, Ajay, and Singh, Parvesh
- Subjects
- *
PETROLEUM waste , *PAENIBACILLUS , *ACINETOBACTER , *POLYVINYL alcohol , *INSULATING oils , *ALGINIC acid - Abstract
Bacterial isolates used for the degradation of waste oils has gained greater interest in recent times since these isolates can be immobilized. However, it's their lack of reproducibility and continual usage that hinders its applicability. The aim of this work is to identify, purify, cultivate and immobilize bacterial isolates that are potential candidates to effectively and selectively degrade waste oils and waste oil blends and reuse them. In an attempt to render bacterium isolates applicable to degradation of lubricating and insulating oil in industrial processes this work investigates the immobilization (through support material, glutaldehyde activated amberlite, polyvinyl alcohol-sodium alginate and chitosan-sodium alginate matrix beads) of bacterial isolates. The data and observed trends show that developed immobilization techniques were successful in immobilizing bacterial isolate strains V2 and D9, with free cell degradation being most efficient (14.7–31.6%) followed by polyvinyl alcohol-sodium alginate (5.3–26.7%), chitosan-sodium alginate (8.8–0.3%) and amberlite-glutaldehyde (2.2–7.0%). The entrapment technique for immobilization of polyvinyl alcohol-sodium alginate and chitosan-sodium alginate proved to be more efficient than adsorption technique used for immobilization of amberlite-glutaldehyde. Free cell degradation was effective in degrading waste oil, but did so upon a single cycle with deterioration. Polyvinyl alcohol-sodium alginate bead matrix can be applied for degradative processes over a wide pH range and short incubation times while chitosan-sodium alginate is best suited for continuous long incubation periods. Reusability of both polyvinyl alcohol-sodium alginate and chitosan-sodium alginate beads are applicable up to a 10-cycle period. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
33. Synthesis, Biological Evaluation, Molecular Docking and Kinetic Investigation of New 2,4,5‐Trisubstituted Imidazole Derivatives as Antidiabetic Agents.
- Author
-
Kumar, Pawan, Syal, Bindu, Seboletswe, Pule, Cele, Nosipho, Olofinsan, Kolawole, Singh, Parvesh, Shahidul Islam, Md., Singh, Deepika, and Gupta, Princy
- Subjects
- *
IMIDAZOLES , *MOLECULAR docking , *HIGH performance liquid chromatography , *ENERGY dispersive X-ray spectroscopy , *X-ray powder diffraction , *HYPOGLYCEMIC agents - Abstract
A series of novel 2,4,5‐trisubstituted imidazole motifs have been synthesized by a magnetically‐tuned halloysite‐supported sulfonic acid catalyst. The prepared supported sulfonic acid catalyst was well characterized by High‐resolution transmission electron microscopy (HR‐TEM), Scanning electron microscopy (SEM), Energy dispersive X‐rays spectroscopy (EDS), Fourier transform infrared (FTIR), X‐ray powder diffraction (XRD), Thermogravimetric analysis (TGA), Brunauer–Emmett–Teller (BET), and Vibrating–sample magnetometry (VSM) techniques; and compounds were confirmed by 1H, 13C‐Nuclear magnetic resonance (NMR) and High resolution mass spectrometry (HRMS) techniques. The purity of compounds was established by High performance liquid chromatography (HPLC). All the prepared compounds were screened for their in vitro antidiabetic activity by using α‐amylase and α‐glucosidase inhibition assay taking acarbose as a reference standard and were found to exhibit significant α‐amylase inhibitory potentials, whereas for α‐glucosidase inhibition, compounds were equipotent to the reference standard. Compound bearing ferrocene moiety was identified as the strongest α‐amylase inhibitor of the series with IC50=47.83±0.63 μM, a five‐fold more potency compared to acarbose (IC50 =269.39±0.29 μM). The presence of substituents in the second position of imidazole pharmacophore plays a key role in inhibitory activity. To find the possible binding interaction of compounds, in silico molecular docking study was performed. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
34. Quinoline–1,3,4-Oxadiazole Conjugates: Synthesis, Anticancer Evaluation, and Molecular Modelling Studies.
- Author
-
Cele, Nosipho, Awolade, Paul, Dhawan, Sanjeev, Khubone, Lungisani, Raza, Asif, Sharma, Arun K., and Singh, Parvesh
- Subjects
- *
MOLECULAR hybridization , *MOLECULAR docking , *MOLECULAR dynamics , *DRUG efficacy , *DRUG design - Abstract
Cancer continues to have overwhelming impacts on human health and the development of new chemotherapeutics. Molecular hybridization has thus been valued as a structure-based drug design approach to drugs with enhanced efficacy. Herein, we report the multistep synthesis of quinoline–2-mercapto-1,3,4-oxadiazole conjugates and their cytotoxicity evaluation. Compound 4j 2-[(5-bromopentyl)thio]-5-[(quinolin-8-yloxy)methyl]-1,3,4-oxadiazole showed the best cytotoxicity to pancreatic (MIA PaCa-2) and colorectal (HCT116) cancer cells with IC50 values of 29.19 ± 0.99 and 75.10 ± 1.87 µM, respectively. The compound is also less cytotoxic to non-cancerous human primary dermal fibroblast cells with IC50 = 91.87 ± 1.29 µM compared to the parent compound 8-hydroxyquinoline (IC50 = 72.36 ± 4.23 µM). ADME properties prediction suggested the drug-likeness of potent compounds while molecular docking and molecular dynamics simulations with doublecortin-like kinase (DCLK1) revealed the compounds' stable binding interactions at the kinase domain. Overall, the results illuminate compound 4j as a structural model to furnish new cytotoxic agents against pancreatic and colorectal cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
35. Secondary echinococcosis.
- Author
-
Kumar Sahu, Shantanu, Singh, Parvesh, Sachan, P. K., and Vijai Bahl, Dig
- Subjects
- *
ECHINOCOCCOSIS , *LIVER diseases , *HYPOCHONDRIA , *EDEMA , *JAUNDICE , *TAPEWORM infections - Abstract
The article presents a discussion of secondary echinococcosis caused by echinococcosis granulosis which commonly affects the liver. It presents the case of a 40-year male cited with a progressive swelling in the right hypochondrium and jaundice. He underwent operation for hepatic hydatid disease 14 years ago.
- Published
- 2006
36. ChemInform Abstract: Triflic Acid Promoted Fries Rearrangement of C-3 Vinyl/isopropenyl-azetidin-2-ones: Single-Pot Synthesis of C-3 Functionalized-2-aryl-2,3-dihydro-quinoline-4(1H)-ones.
- Author
-
Mehra, Vishu, Singh, Parvesh, Bisetty, Krishna, and Kumar, Vipan
- Subjects
- *
QUINOLINE derivatives , *ISOQUINOLINE , *ISOPROPENYL compounds , *AZETIDINE , *LOW temperatures , *TAUTOMERISM - Abstract
At lower reaction temperatures the corresponding tautomer of (II) can be isolated alongside. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
37. ChemInform Abstract: β-Lactam-Synthon-Interceded Facile Synthesis of Functionally Decorated Thiohydantoins.
- Author
-
Mehra, Vishu, Singh, Parvesh, Manhas, Neha, and Kumar, Vipan
- Subjects
- *
AMINO acid synthesis , *CHEMICAL synthesis , *LACTAMS - Abstract
An abstract of the article "ß-Lactam-Synthon-Interceded Facile Synthesis of Functionally Decorated Thiohydantoins" by V. Mehra, P. Singh, N. Manhas and V. Kumar is presented.
- Published
- 2014
- Full Text
- View/download PDF
38. One-pot synthesis of 1-substituted 1H-1,2,3,4-tetrazoles from 2-aminothiazoles using tributylmethylammonium chloride as a catalyst.
- Author
-
Nagaraju, Kerru, Lalitha, Gummidi, Singh, Parvesh, and Rao, Chunduri Venkata
- Subjects
- *
TETRAZOLES , *ORGANONITROGEN compounds , *CATALYSTS , *CHEMICAL reactions , *AROMATIC compounds - Abstract
Reaction between substituted thiazolylamine or oxazolylamine, triethyl orthoformate and sodium azide in the presence of tributylmethylammonium chloride in DMSO furnishes 1-substituted 1H-1,2,3,4-tetrazole in high yield. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
39. ChemInform Abstract: β-Lactam-Synthon-Interceded Synthesis of Isatin-Imidazolidine-2-thione Conjugates with Structural Validation Using Molecular Dynamic Simulations and Cytotoxic Evaluation.
- Author
-
Nisha, Nisha, Singh, Parvesh, Hendricks, Denver T., Bisetty, Krishna, and Kumar, Vipan
- Subjects
- *
ANIONS , *ISATIN , *THIONES , *ISOCYANATES , *MOLECULAR dynamics , *ESOPHAGEAL cancer , *CELL lines - Abstract
The anion derived from isatins (I) reacts with isocyanates (II) to form imidazolidine-2-thiones (III), some of which show significant cytotoxic activity against the oesophageal cancer cell line WHCO1. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
40. ChemInform Abstract: Synthetic Studies on the Role of Substituents at C-3 Position on C3-C4 Bond Cleavage of β-Lactam Ring: Convenient Route for Diastereoselective Synthesis of Pyridin-2-ones.
- Author
-
Singh, Pardeep, Singh, Parvesh, Kumar, Kewal, Kumar, Vipan, Mahajan, Mohinder P., and Bisetty, Krishna
- Abstract
The effect of various electron withdrawing as well as electron donating substituents on the C3-position on the C3/C4 bond cleavage is studied. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
41. Design, synthesis, and identification of a novel napthalamide-isoselenocyanate compound NISC-6 as a dual Topoisomerase-IIα and Akt pathway inhibitor, and evaluation of its anti-melanoma activity.
- Author
-
Karelia, Deepkamal N., Sk, Ugir Hossain, Singh, Parvesh, Gowda, A.S. Prakasha, Pandey, Manoj K., Ramisetti, Srinivasa R., Amin, Shantu, and Sharma, Arun K.
- Subjects
- *
NAPHTHALIMIDES , *PROTEIN kinase B , *DRUG synthesis , *DRUG design , *CELL survival - Abstract
Synthesis and anti-melanoma activity of novel naphthalimide isoselenocyanate (NISC) and naphthalimide selenourea (NSU) analogs are described. The novel agents were screened for growth inhibition of different human melanoma cell lines including those having BRAF V600E mutation (UACC903, 1205Lu, and A375M) and BRAF WT (CHL-1). In general, the NISC analogs (4a-d) were more effective in inhibiting the cell viability than the NSU analogs (7a-b) . Overall, NISC-6 (4d) , having a six-carbon alkyl chain, was identified as the most cytotoxic compound in both BRAF V600E mutated and BRAF WT cells. NISC-6 docked strongly into the binding sites of Akt1 and human topoisomerase IIα (Topo-IIα), and the docking results were supported by experimental findings showing NISC-6 to inhibit of both Akt pathway and Topo-IIα activity in a dose dependent manner. Furthermore, NISC-6 effectively induced apoptosis in human melanoma cells, inhibited tumor growth by ∼69% in a melanoma mouse xenograft model, and showed excellent compliance with the Lipinski’ rule of five, suggesting both its efficacy and drug-like behavior under physiological conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
42. Synthesis and structure elucidation using 2D NMR and thermal coefficient investigation on amino acid tethered quinoxalines.
- Author
-
Shintre, Suhas A., Ramjugernath, Deresh, Singh, Parvesh, and Koorbanally, Neil A.
- Subjects
- *
QUINOXALINES , *AMINO acids , *NUCLEAR magnetic resonance , *HYDROGEN bonding , *DENSITY functional theory , *MOLECULAR dynamics , *X-ray diffraction - Abstract
The article discusses the study regarding the synthesis and structure elucidation of amino acid tethered quinoxalines through two-dimensional nuclear magnetic resonance (NMR) and thermal coefficient investigation. Topics discussed include the analysis of the hydrogen bonding tendency and conformational flexibility through density functional theory (DFT) and molecular dynamic (MD) simulations, the proton resonances of quinoxaline structure, and the use of single-crystal X-ray diffraction.
- Published
- 2016
- Full Text
- View/download PDF
43. Serendipitous synthesis of 2,3-dihydroquinazolin-4(1H)-ones in ZnCl2/urea deep eutectic solvent.
- Author
-
Kumar, Gobind, Khubone, Lungisani, Seboletswe, Pule, Manhas, Neha, Makhanya, Talent, Bhargava, Gaurav, and Singh, Parvesh
- Subjects
- *
EUTECTICS , *SOLVENTS , *SUSTAINABLE chemistry , *FUNCTIONAL groups , *BENZALDEHYDE , *HETEROCYCLIC compounds - Abstract
A green, sustainable, and efficient one-pot, synthetic strategy for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones (DHQs) was developed. The ZnCl2/urea used as a deep eutectic solvent (DES) not only efficiently promoted the condensation between isatoic anhydride and benzaldehyde but unexpectedly acted as a nitrogen source (like ammonia) in situ to afford DHQs in excellent yields. This approach offers remarkable advantages, involving the triple role of DES in the synthesis of DHQs, atom-economical, green organocatalysts, metal-free conditions, cost-effectiveness, and tolerance to a range of functional groups. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
44. The Multi‐Biological Targeted Role of Dehydrozingerone and its Analogues.
- Author
-
Kumar, Vishal, Bala, Renu, Dhawan, Sanjeev, Singh, Parvesh, and Karpoormath, Rajshekhar
- Subjects
- *
STRUCTURE-activity relationships , *CURCUMIN , *SCIENTIFIC community , *CLINICAL trials , *SOLUBILITY - Abstract
Curcumin (Cur) has shown its potential in the treatment of a wide variety of ailments. As a result, several investigations on curcumin have been conducted in vitro, in vivo, and in clinical trials. Regrettably, researchers have largely lost interest in this excellent scaffold due to its chemical instability, poor solubility, and rapid metabolism, which directly affect its pharmacological properties. Alternatively, the researchers are working on it to improve the solubility and biological half‐life, it is one of the most researched natural phytochemical to date. Among these, Dehydrozingerone (DZG), a curcumin half structure has garnered considerable research interest due to a wide spectrum of its biological activities. Thus, this study offers insight into the pharmacological activity of modified DZG conjugates (incorporate multiple effective modifications to the various positions), which have been developed since 2016. Additionally, the structure‐activity relationship (SAR) of DZG hybrids was illustrated for their specific pharmacological properties. This review presents an update for the scientific community, which could assist in addressing the gaps, challenges and pharmacological aspects of DZG. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
45. α-Glucosidase and α-Amylase Inhibitory Potentials of Quinoline–1,3,4-oxadiazole Conjugates Bearing 1,2,3-Triazole with Antioxidant Activity, Kinetic Studies, and Computational Validation.
- Author
-
Cele, Nosipho, Awolade, Paul, Seboletswe, Pule, Olofinsan, Kolawole, Islam, Md. Shahidul, and Singh, Parvesh
- Subjects
- *
ALPHA-glucosidases , *ANTIOXIDANTS , *AMYLASES , *MOLECULAR dynamics , *PROTEIN-ligand interactions , *GALLIC acid , *MOLECULAR docking , *METABOLIC disorders - Abstract
Diabetes mellitus (DM) is a multifaceted metabolic disorder that remains a major threat to global health security. Sadly, the clinical relevance of available drugs is burdened with an upsurge in adverse effects; hence, inhibiting the carbohydrate-hydrolyzing enzymes α-glucosidase and α-amylase while preventing oxidative stress is deemed a practicable strategy for regulating postprandial glucose levels in DM patients. We report herein the α-glucosidase and α-amylase inhibition and antioxidant profile of quinoline hybrids 4a–t and 12a–t bearing 1,3,4-oxadiazole and 1,2,3-triazole cores, respectively. Overall, compound 4i with a bromopentyl sidechain exhibited the strongest α-glucosidase inhibition (IC50 = 15.85 µM) relative to reference drug acarbose (IC50 = 17.85 µM) and the best antioxidant profile in FRAP, DPPH, and NO scavenging assays. Compounds 4a and 12g also emerged as the most potent NO scavengers (IC50 = 2.67 and 3.01 µM, respectively) compared to gallic acid (IC50 = 728.68 µM), while notable α-glucosidase inhibition was observed for p-fluorobenzyl compound 4k (IC50 = 23.69 µM) and phenyl-1,2,3-triazolyl compound 12k (IC50 = 22.47 µM). Moreover, kinetic studies established the mode of α-glucosidase inhibition as non-competitive, thus classifying the quinoline hybrids as allosteric inhibitors. Molecular docking and molecular dynamics simulations then provided insights into the protein–ligand interaction profile and the stable complexation of promising hybrids at the allosteric site of α-glucosidase. These results showcase these compounds as worthy scaffolds for developing more potent α-glucosidase inhibitors with antioxidant activity for effective DM management. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
46. An ultrasensitive performance enhanced novel cytochrome c biosensor for the detection of rebaudioside A.
- Author
-
Bathinapatla, Ayyappa, Kanchi, Suvardhan, Singh, Parvesh, Sabela, Myalowenkosi I., and Bisetty, Krishna
- Subjects
- *
BIOSENSORS , *CYTOCHROME c , *STEVIOSIDE , *CHEMICAL detectors , *ELECTROCHEMICAL sensors - Abstract
In this study a novel cyctochrome c modified nanocomposite electrochemical biosensor was developed for the electrochemical determination of rebaudioside A in different food samples. The electrode surface was fabricated with graphene oxide assimilated with gold nanoparticles decorated on multiwalled carbon nanotubes/cytochrome c. The developed biosensor exhibited a 10-fold enhancement in the differential pulse voltammetry signal carried out at pH 11.0 in a 0.1 M borate buffer. Under the optimized conditions, I p (µA) was proportional to the rebaudioside A concentration in the range of 0.001–0.05 mM ( R 2 =0.8308) and 0.075–1.25 mM ( R 2 =0.9920) with a detection limit ( S / N =3) of 0.264 µM. Results of this study revealed that cyctochrome c was adsorbed tightly onto the surface of the modified electrode and showed an enzymatic catalytic activity towards the quasi-reversible reduction of rebaudioside A at −0.1 V (vs Ag/AgCl). The direct electron transfer by cytochrome c was further supported by HOMO-LUMO calculations performed at the density functional theory level. Additionally, the molecular docking simulations predicted a stronger binding affinity of rebaudioside A towards cytochrome c, thus supporting their host-guest relationship. The use of novel electrode materials in this study demonstrates the application of the electrochemical biosensor in the food industry. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
47. Fabrication of copper nanoparticles decorated multiwalled carbon nanotubes as a high performance electrochemical sensor for the detection of neotame.
- Author
-
Bathinapatla, Ayyappa, Kanchi, Suvardhan, Singh, Parvesh, Sabela, Myalowenkosi I., and Bisetty, Krishna
- Subjects
- *
METAL fabrication , *COPPER , *METAL nanoparticles , *MULTIWALLED carbon nanotubes , *ELECTROCHEMICAL analysis , *CARBON electrodes , *DITHIOCARBAMATES - Abstract
A highly sensitive and novel electrochemical sensor for the detection of neotame using differential pulse voltammetry with a modified glassy carbon electrode is presented. The method was further customized by the fabrication of the electrode surface with copper nanoparticles–ammonium piperidine dithiocarbamate–mutiwalled carbon nanotubes assimilated with β-cyclodextrin. The multiwalled carbon nanotubes assimilated with β-cyclodextrin/glassy carbon electrode exhibited catalytic activity towards the oxidation of neotame at a potential of 1.3 V at pH 3.0. The transmission electron microscopy, thermogravimetric analysis, frontier transform infrared spectroscopy and cyclic voltammetry were employed to characterize the electrochemical sensor. The sensitivity and detection limits of the electrode increased two-fold in contrast to the β-CD-MWCNTs/GCE sensor. The developed method was successfully applied for the determination of neotame in food samples, with results similar to those achieved by our modified capillary electrophoresis method with a 96% confidence level. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
48. Analytical evaluation of steviol glycosides by capillary electrophoresis supported with molecular docking studies.
- Author
-
Ayyappa, Bathinapatla, Kanchi, Suvardhan, Singh, Parvesh, Sabela, Myalowenkosi, Dovey, Martin, and Bisetty, Krishna
- Subjects
- *
STEVIOSIDE , *CAPILLARY electrophoresis , *MOLECULAR docking , *ELECTROKINETICS , *CHROMATOGRAPHIC analysis , *STANDARD deviations , *CHEMICAL affinity , *HYDROGEN bonding - Abstract
This paper reports on a newly developed electrokinetic chromatographic method for the simultaneous separation and determination of steviol glycosides in real stevia samples by capillary electrophoresis and supported by molecular docking studies. Our results obtained using 30-mM heptakis-(2,3,6-tri- o-methyl betacyclodextrin) as a separating agent, suggest that at optimum experimental conditions the detection limits of 2.017 × 10 and 7.386 × 10 M and relative standard deviations ( n = 5) of 1.10 and 1.17 were obtained for rebaudioside-A and stevioside, respectively. In addition, the molecular docking studies explained to a certain extent why the separation was successful. The calculated binding free energy results for the rebaudioside-A and stevioside complexes formed with the separating agent showed that although both ligands penetrated deeply into the hydrophobic cavity of the separating agent, the presence of additional hydrogen bonding in the case of stevioside is probably responsible for its stronger binding affinity than that of rebaudioside-A. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
49. Determination of Neotame by High-Performance Capillary Electrophoresis Using ß-cyclodextrin as a Chiral Selector.
- Author
-
Bathinapatla, Ayyappa, Kanchi, Suvardhan, Singh, Parvesh, Sabela, MyalowenkosiI., and Bisetty, Krishna
- Subjects
- *
CAPILLARY electrophoresis , *CYCLODEXTRINS , *ELECTROKINETICS , *MOLECULAR docking , *FOOD chemistry , *CHROMATOGRAPHIC analysis , *DIASTEREOISOMERS - Abstract
An electrokinetic chromatographic method was developed for the chiral separation of neotame, a new high intensity artificial sweetener, using a chiral separating agent heptakis 2,3,6-tri-o-methylbetacyclodextrin. The purpose of this study was to better understand diastereomer-resolution interactions between neotame and the chiral separating agent. Molecular docking studies were performed to elucidate the mechanism of the separation. The optimum conditions were 50 mM phosphate buffer, pH 5.5, applied voltage 20 kV, cassette temperature of 30°C, and a 4 s sample injection time. The calibration curve showed good linearity (r2 > 0.99) with recoveries for both diastereomers, ranging from 95.66–99.00% and the limits of detection for L,L-neotame and D,D-neotame were 0.01857 and 0.08214 mM, respectively. The developed method showed analytical precision with relative standard deviations (n = 5) of 1.20% and 1.17% with respect to migration time and peak area, respectively. A large difference in the interaction energies observed between the diastereomers represents a significant differentiation. The results showed that both electrostatic and hydrophobic interactions played a significant role in stabilizing their inclusion complexes and consequently supported the elution order based on their differential stabilities. [ABSTRACT FROM PUBLISHER]
- Published
- 2014
- Full Text
- View/download PDF
50. Creation of thermostable and alkaline stable xylanase variants by DNA shuffling.
- Author
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Stephens, Dawn Elizabeth, Khan, Faez Iqbal, Singh, Parvesh, Bisetty, Krishna, Singh, Suren, and Permaul, Kugen
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HEAT stability in proteins , *ALKALINE solutions , *XYLANASES , *DNA analysis , *GENETIC mutation , *MUTAGENESIS - Abstract
Mutant xylanases, G41 and G53, were generated by random mutagenesis of Thermomyces lanuginosus xylanase DSM 5826 ( xyn A) in a previous study. Incubation at 90 min showed that G41 had 75% activity at 80 °C and G53 had 93% activity at pH 10. In order to create xylanase variants possessing both thermal and alkaline stability in a single enzyme, G41 and G53 served as templates for DNA shuffling using the StEP recombination method. One of the resulting StEP recombinants, S340, retained 54% stability at 80 °C and 60% stability at pH 10 with three resulting amino acid mutations. Another StEP recombinant, S325, displayed 85% stability at 80 °C and 60% stability at pH 10 and DNA sequencing showed that it inherited mutations from both parents. All thermostable variants displayed an increase in arginine content with poor enzyme activity. Thus, the StEP recombination method successfully recombined mutations into two xylanases that were more robust than their parent counterparts. Additionally, the 3D-models of the wild type T. lanuginosus xyn A (xyl_ext) and its variants, G41 and S325, were predicted using I-TASSER and then subjected to molecular dynamics (MD) simulations at 300 K for a deeper understanding of their structural features. The results from the predicted 3D models show clearly the presence of α-helical regions in the N-terminal residues of the xyl_ext, G41 and S325. Moreover, the MD analysis suggests that the presence of additional residues (1–31) and point mutation induces slight structural changes with the stability of the protein being evenly distributed over the whole structure. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
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