Browsing by Author "Vishal Prasad Sharma"

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Design, synthesis and in-silico & in vitro enzymatic inhibition assays of pyrazole-chalcone derivatives as dual inhibitors of α-amylase & DPP-4 enzyme
(Springer Science and Business Media Deutschland GmbH, 2022) Manisha Nidhar; Priyanka Sonker; Vishal Prasad Sharma; Sanjay Kumar; Ashish Kumar Tewari
A series of pyrazole-chalcone derivatives were designed, synthesized and evaluated for their in vitro α-amylase & DPP-4 inhibitory activity. The structure of the compounds thus prepared was confirmed by analytical, and spectral techniques, 1H-NMR, 13C-NMR and Mass spectroscopy. To preliminarily investigate the molecular targets and to confirm the experimental activity testing for these anti-diabetic compounds, the molecular docking studies were determined, using different target receptors i.e., DPP-4 (PDB: 2OLE), PPARγ (PDB: 5Y2O) & α-amylase enzyme (PDB: 5E0F). The docking study results revealed that pyrazole-chalcone derivatives exhibited better binding interaction to α-amylase enzyme over the DPP-4 enzyme & PPARγ. Depending on in silico experiments the designed compounds were selectively prioritized for synthesis. The synthesized compounds were subjected to enzyme-based in vitro α-amylase, DPP-4 inhibitory, and antioxidant activity. ADMET parameters like HBD, HBA, PSA, cLogP, molecular weight, bioavailability, and drug-likeness further confirmed that the compounds are potential lead compounds for future study. Compounds 4d and 6a exhibited highest activity toward α-amylase enzyme and DPP-4 enzyme. © 2021, Institute of Chemistry, Slovak Academy of Sciences.
Designing DPP-4 inhibitors: Synthesis, characterization, in silico & in vitro evaluation, and theoretical calculation of flexible compounds linked via ortho xylyl spacers
(Elsevier B.V., 2025) Vipin Kumar; Manisha Nidhar; Muhammad Sheraj; Vishal Prasad Sharma; Priya Gupta; Rahul Kumar Singh; Ashish Kumar Tewari
In this study, 1,2,3-triazole-containing six symmetrical flexible dimer compounds (5a-5f) linked via ortho xylyl spacers were synthesized using a copper-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction. Triazinone, isatin, and pyridazinone moieties were utilized to synthesize the heteroaromatic terminal alkynes (3a-3f). The structural characterization of all compounds was performed using spectroscopic techniques, including SCXRD, 1H and 13C-NMR, IR, and HRMS spectrometry. Among these compounds, compound 5a was crystallized, showing two twisted boat-type geometries at an angle of 43.98 degrees. Moreover, we investigated the intra- and intermolecular contact preserving the crystal packing in the solid state. Hirshfeld surface analysis and its related 2-D fingerprint plots control the percentage contribution of intermolecular contact. The in silico study of these compounds was conducted and revealed that 5d and 5c have good docking scores and interactions; further, all these compounds were validated by in vitro DPP-4 inhibitory activity. DPP-4 inhibition revealed that compound 5d has an IC50 value of 1.57 nM, similar to the standard drug sitagliptin. Compound 5d could be a potent DPP-4 inhibitor with antidiabetic potential for further investigation. © 2025
Designing symmetrically folded scaffolds of pyridazinone and triazinone derivatives linked via N,N-diethyl-4-nitro-benzenesulfonamide to explore luminescent materials
(Royal Society of Chemistry, 2025) Vipin Kumar; Krishanu Bandyopadhyay; Manisha Nidhar; Vishal Prasad Sharma; Priyanka Yadav; Suman Gill; Priyanka K. Sonker; Abhineet Verma; Satyen Saha; Ashish Kumar Tewari
The study investigates π⋯π interaction in an aromatic-heteroaromatic folded scaffold as well as (NO)π⋯π(arene) and O⋯π(arene) of pyridazinone and 1,2,4-triazinone and their implication for the design of luminescent materials. The research is focused on elucidating the materials' emission spectra and specifically emphasizing the donor-accepter stacking phenomena in the synthesized compounds by altering heteroaromatic units. The studies enlightened the effect of the methoxy group on emission spectra obtained by flipping the DPM molecule in the liquid and solid phases. Results highlight the importance of intramolecular and intermolecular interactions in determining the optical and electrical properties of organic materials. The full spectral profile and quantum yield (φ) of all compounds were examined in the liquid state. Crystallographic data for compounds DP, DT, DPM, and DTM are presented, highlighting the distinct conformers and stacking strength and affirming the stability of crystal geometry. Furthermore, theoretical studies established the correlation between molecular structure and the absorption spectra of molecules. © 2025 The Royal Society of Chemistry.
Na2S·9H2O mediated facile synthesis of 1,3-dihydrofuro[3,4-b]quinoline derivatives via domino reduction approach
(Elsevier Ltd, 2021) Rashmi Singh; Tanu Gupta; Vishal Prasad Sharma; Radhey M. Singh; Ashish Kumar Tewari
A simple, highly efficient method for synthesis of 1,3-dihydrofuro[3,4-b]quinoline is described by the reaction of o-arylalkynyl quinoline aldehydes with Na2S·9H2O via domino reduction approach. The method is simple and proceeds under mild condition under an air atmosphere to give 1,3-dihydrofuro[3,4-b]quinoline in good to excellent yields. The beauty of the reaction is cyclization as well as reduction has been taken place in the same reaction pot. Also the conversion of aldehyde into primary alcohol has been discussed under the same reaction condition. © 2021
Novel pyrimido-pyridazine derivatives: design, synthesis, anticancer evaluation and in silico studies
(Newlands Press Ltd, 2022) Priyanka Sonker; Mamata Singh; Manisha Nidhar; Vishal Prasad Sharma; Priyanka Yadav; Rashmi Singh; Biplob Koch; Ashish Kumar Tewari
Aim: A novel pyrimido-pyridazine derivative for developing anticancer agents was synthesized via Ullmann arylation using an efficient Cu(OAc)2 catalyst. Materials & methods: Compounds were investigated for their anticancer potential, against human breast adenocarcinoma cells, viz. MCF-7, MDA-MB-231 and normal cell line HEK-293. Further, an in vivo study was conducted on lymphoma-bearing mice while in silico analysis was carried out for molecular interactions. Results: Compound 2b displayed significant antitumor activity towards MDA-MB-231 cells through induction of apoptosis and arresting cells in S-phase in vitro, while it significantly increased the lifespan and reduced tumor growth in vivo. An in silico study revealed potent tyrosine-protein kinase inhibitors. Conclusion: Taken together the molecule has the potential to become an effective therapeutic treatment for breast cancer. © 2022 Newlands Press.
One pot synthesis of 4-iodo-3-phenylbenzo[b][1,6]naphthyridine via imino iodization-cyclization of alkynylquinoline-3-carbaldehydes
(Taylor and Francis Ltd., 2024) Rashmi Singh; Vishal Prasad Sharma; Rajesh Kumar; Manish Raj; Tanu Gupta
Simple, environmentally benign and metal free one pot strategy has been used for the synthesis of 4-iodo-3-phenylbenzo[b][1,6]naphthyridine from O-alkynylquinolinyl aldehydes with tert-butyl amine and iodine through imine formation in good to excellent yield at room temperature in aerobic and mild conditions. The beauty of this reaction is the imine formation and cyclization in the same reaction pot. Due to presence of iodine in product, it can be useful for further reaction and can be valuable synthon for new organic compounds. © 2024 Taylor & Francis Group, LLC.
Preparation, structure and dimerization of molecular tweezer: Cyanuric acid core based flexible symmetric linked pthalimide moiety as a heteroaromatic system
(Elsevier B.V., 2022) Archana Gaurav; Vishal Prasad Sharma; Priyanka Sonker; Ashish Kumar Tewari
Here, we synthesize tripodal tweezer molecule which have cyanuric acid in the center, propylene as a linker and pthalimide hetrocycle as terminal for conformational applications. The propylene linker promote intramolecular and intermolecular interactions within and encircle molecules. Appropriately, the geometrical specification set for the molecules which must be concert about conformations in different states. The conformational studies of this tripodal compound has been carried by X-ray crystallography. Evaluation of conformational stability in different conformation through theoretical calculations has been done. © 2021 Elsevier B.V.
Sodium sulphide promoted synthesis of fused quinoline at room temperature
(Royal Society of Chemistry, 2021) Rashmi Singh; Vishal Prasad Sharma; Priyanka Yadav; Priyanka Sonker; Radhey Mohan Singh; Ashish Kumar Tewari
A novel, simple and eco-friendly strategy for the synthesis of thiopyrano[4,3-b]quinolin-1-ones and pyrrolo[3,4-b]quinolin-1-ones from 2-alkynylquinoline-3-carbonitriles and sodium sulphide (Na2S·9H2O) under catalyst-free conditions at room temperature has been described. In this reaction, a readily available inorganic salt (Na2S·9H2O) serves as the sulphur source and leads to the generation of diverse functionalized thiopyrano[4,3-b]quinolin-1-ones and pyrrolo[3,4-b]quinolin-1-ones in moderate to excellent yields through sulfuration, annulation, and aerial oxidation. © The Royal Society of Chemistry 2021.
Synthesis, crystal structure, Hirshfeld surface analysis, DFT investigation, and molecular docking, of novel organic dithiocarbamates obtained from Baylis-Hillman adducts/alcohols at room temperature
(Elsevier B.V., 2024) Vishal Prasad Sharma; Vipin Kumar; Rashmi Singh; Priyanka Sonker; Priyanka Yadav; Mohammad Kashif; Archana Gaurav; Ashish Kumar Tewari
Several new organic dithiocarbamates were produced in aqueous ethanol using a one-pot multicomponent reaction involving Baylis-Hillman adducts/alcohols, CS2, and different secondary amines. Because of the short reaction periods and high yields, this approach is easy, green, and cost-effective for producing biologically relevant dithiocarbamates at room temperature. The structure of the synthesized dithiocarbamates was confirmed using 1H, 13C NMR, HRMS, and single-crystal X-ray diffraction methods. The HOMO–LUMO energy gap, Mulliken charges, and MESPs have all been computed and presented. Hirshfeld surface analysis and accompanying two-dimensional fingerprint plots, as well as compound interaction energy estimates, were employed as theoretical methodologies to examine the driving force for crystal structure development via intermolecular interactions in their crystal lattices. A molecular docking study was also performed to evaluate the probable interactions and binding manner of the newly synthesized compounds (4a-4w) to the E. coli nitroreductase enzyme. The docking analysis suggested that the compounds (4k, 4g, 4l, and 4m) may inhibit the activity of the nitroreductase enzyme of E. coli. © 2024 Elsevier B.V.
The development of a robust folded scaffold as a fluorescent material using butylidine-linked pyridazinone-based systems via aromatic π⋯π stacking interactions
(Royal Society of Chemistry, 2022) Priyanka Yadav; Abhineet Verma; Vishal Prasad Sharma; Rashmi Singh; Tarun Yadav; Ranjeet Kumar; Shiv Pal; Hariom Gupta; Satyen Saha; Ashish K. Tewari
Fluorescence-capable robust folded pyridazinone-based homo- and heterodimers linked with butylidine linkers, whose crystals exhibit fluorescence with quantum yields of 11% (1CN) and 28% (2CN) due to intramolecular stacking, were synthesized. Previous reports state that intramolecularly folded/stacked compounds result in immediate quenching with no fluorescence, but we have designed two intramolecularly stacked compounds that show suitable emission spectra due to charge transfer between two conjugated heteroaromatic rings. Full spectral profiles and quantum yields of the organic solid-state emitters are reported. The optical behavior of pyridazinone and the triazinone-related homo- and heterodimers was rationalized based on time-dependent density functional theory (TD-DFT) studies, and the observed stacking interactions in crystals were studied in detail. This work demonstrates the significance of cyanoaromatics in the design of solid-state organic fluorescent materials. Herein, we report that the intramolecular folding nature of organic solid-state materials has an important effect on their photophysical and charge transfer properties. Hence, our insights pinpoint the importance of charge transfer between π-stacked folded dimers. © 2022 The Royal Society of Chemistry
The enthralling effect of packing on the light emission of pyridazinone based luminophore: Crystallographic, electronic absorption and computational studies.
(Elsevier B.V., 2022) Priyanka Yadav; Abhineet Verma; Priyanka Sonker; Vishal Prasad Sharma; Akhilesh Kumar; Tarun Yadav; Shiv Pal; Satyen Saha; A.K. Tewari
The present study unfolds the synthesis and characterization of a new butylidine linked hetero dimer of pyridazinone (PNP). The crystal structure analysis of PNP reveals that it exhibited infinite 1D linear chains connected through C-H∙∙∙O interaction and interlayer connectivity was supported by the unconventional orthogonal dipolar interaction via nitro-aromatic (ONO2···π(C)Ar). These interactions are also described using DFT calculations and are potentially studied. Here we discuss the influence of crystal structure on the photophysical properties of a new solid state emitter containing brick layer packing. Furthermore, we conducted detailed exploration of the intermolecular interactions that maintain the crystal packing of the structure by employing the Hirshfeld surface analysis and its corresponding two-dimensional fingerprint plots revealing that the C-H∙∙∙O interaction mainly stabilized the crystal structure. Time-dependent density functional theory (TDDFT) studies and observed nitro aromatic interactions (ONO2∙∙∙(C)Ar) in the crystal helped to explain the electronic behaviour of PNP. The validity of the computations is supported by a good agreement between the estimated and experimental values of the excitation energy transfer. Furthermore, we conducted detailed research on the Hirshfeld surface analysis and the intermolecular interactions that stabilize the crystal packing using their corresponding two-dimensional fingerprint plot. Some standard thermodynamical parameters such as specific heat, entropy and free energy have also been computed. In addition to this, the variation of specific heat with temperature has been explored. © 2022 Elsevier B.V.
Ultrasound-assisted ring opening of epoxides in HFIP: THF: Synthesis, characterization, computational studies and molecular docking of novel 2‑hydroxy dithiocarbamates
(Elsevier B.V., 2024) Vishal Prasad Sharma; Manisha Nidhar; Muhammad Sheraj; Vipin Kumar; Priyanka Sonker; Amit Patel; Suman Gill; Sooraj Sura; Ashish Kumar Tewari
Under the influence of ultrasonic irradiation, pyridazinone, triazinone, or phthalimide containing 2‑hydroxy dithiocarbamates, a biologically relevant novel organo-sulfur compound, was synthesized. Detailed characterization, computational, and molecular docking studies are being investigated. Molecular interactions were studied using 3D Hirshfeld surfaces and corresponding 2D fingerprint plots. Theoretical (DFT) studies on the molecular structure, HOMO, LUMO, and quantum chemical descriptors were performed at the B3LYP/6–311++G(d,p) level of theory. At the same time, the interaction energy was computed using the B3LYP/6–31G(d,p) level of theory. The FMO study revealed that molecules 4a and 4p in the gas phase have 3.545 eV and 3.263 eV HOMO-LUMO energy gaps, respectively, and they are hence kinetically stable. Quantum chemical calculations confirm the electrophilic character of compounds 4a and 4p, as the molecule is stable and highly electrophilic. The interactions of 2‑hydroxy dithiocarbamate derivatives (4a-4t) with the ligand-binding site of the target COX-2 (cyclooxygenase-2) enzyme were investigated using in-silico molecular docking experiments. Compared to the standard medicine celecoxib, the results showed that most synthesized derivatives had better glide scores and interaction. The docking study of all the synthesized compounds revealed that compounds 4a, 4e, and 4o interact well with the COX-2 enzyme as anti-inflammatory drugs. Molecular dynamic simulation was utilized to validate the docking study and explore the stable binding site and interaction of compound 4o, which is the most potent. The findings indicated that compound 4o exhibited better stability and interaction when compared to the reference drug. © 2024 Elsevier B.V.
Utilizing Baylis–Hillman Adducts Followed by Michael Addition/Elimination Reaction for the Synthesis of Unusual Conformationally Stable Molecules Governed by Aromatic Interactions
(John Wiley and Sons Inc, 2023) Vishal Prasad Sharma; Vipin Kumar; Priyanka Sonker; Priyanka Yadav; Rashmi Singh; Ramachandran Gnanasekaran; Ashish Kumar Tewari
The compounds under investigation sought a new approach to synthesis via the Baylis-Hillman (B−H) and Michael addition reactions. The product formation‘s legitimacy was tested using a repeat reaction with many different nucleophiles. The additional stability of the product via aromatic π⋅⋅⋅π and C−H⋅⋅⋅π interactions may result in unexpected product formation in diverse reactions undertaken utilizing different starting materials. This study suggests that weak interaction not only provides selectivity during reactions but also modifies the result. © 2023 Wiley-VCH GmbH.