Browsing by Author "Manisha Nidhar"

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Click inspired novel pyrazole-triazole-persulfonimide & pyrazole-triazole-aryl derivatives; Design, synthesis, DPP-4 inhibitor with potential anti-diabetic agents
(Academic Press Inc., 2022) Manisha Nidhar; Shaziya Khanam; Priyanka Sonker; Priya Gupta; Archisman Mahapatra; Swaraj Patil; Brijesh Kumar Yadav; Rahul Kumar Singh; Ashish Kumar Tewari
This work presented the first report on designing, synthesizing of novel pyrazole-triazole-persulfonimide (7a-i) and pyrazole-triazole-aryl derivatives (8a-j) via click reaction using CuI catalyst and evaluated for their anti-diabetic activity and DPP-4 inhibitory effect. Click reactions went smoothly with CuI catalyst in the presence of tridentate chelating ligands and produced copper-free target pyrazole-triazole-persulfonimide analogues in excellent yield at RT. The designed compounds were docked against DPP-4 enzyme and showed excellent interaction with active amino acids residue. Further, all novel pyrazole-triazole-persulfonimide and pyrazole-triazole derivatives were subjected to enzyme-based in vitro DPP-4 inhibitory activity. Based on the SAR study DPP-4 inhibitory capacity compounds 7f (9.52 nM) and 8h (4.54 nM) possessed the significant inhibition of DPP-4. Finally compounds 7f and 8h were evaluated for their in vivo anti-diabetic activity using STZ induced diabetic mice model, and 8h showed a significant diabetic control effect compared to the sitagliptin drug. These studies demonstrated that the novel pyrazole-triazole-persulfonimide and pyrazole-triazole-aryl derivatives might be used as the leading compounds to develop novel DPP-4 inhibitors as potential anti-diabetic agents. © 2022 Elsevier Inc.
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.
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.
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.
Diabetes Mellitus
(Elsevier, 2025) Manisha Nidhar; Ashish Kumar Tewari
Diabetes Mellitus: Target Enzymes and Drugs highlights the importance of different targets in lead drug discovery and the importance of the synthesis of lead analogues. The book discusses the role of target enzymes, receptors, and related drugs in diabetes mellitus that are necessary for research on improving solutions for diabetes care. This unique resource provides information about all enzymes or receptors involved in diabetes pathophysiology to help describe target enzymes and potent antidiabetic drugs to improve patient care. This type of research is needed for the understanding of the effects of drugs in order to improve future treatments and care of patients with diabetes. © 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
Introduction to diabetes mellitus
(Elsevier, 2025) Manisha Nidhar; Sooraj Sura; Vipin Kumar; Ashish Kumar Tewari
Diabetes mellitus is a group of metabolic disorders that involve hyperglycemia caused by defects in the production of insulin, its action, or both. Diabetes mellitus is primarily divided into type-1 diabetes and type-2 diabetes. Type-1 diabetes is typically treated with insulin therapy and is also known as insulin-dependent diabetes mellitus, whereas type-2 diabetes is commonly treated with oral antidiabetic agents. Sulphonylureas, biguanides, insulin sensitizers, glucosidase inhibitors, dipeptidyl peptidase-4 inhibitors, and sodium-glucose cotransporter-2 inhibitors are the main drugs used to treat type-2 diabetes. Patients who are unable to accomplish treatment goals with first-line oral antidiabetic agents as monotherapy frequently receive prescriptions for dual medication therapy. This chapter, have made an effort to study the brief about different target enzymes of type-2 diabetes, management, mode of action of drugs as well as their adverse effects. © 2025 Elsevier Inc. All rights reserved.
Lead modification via computational studies: Synthesis of pyrazole-containing β-amino carbonyls for the treatment of type 2 diabetes
(John Wiley and Sons Inc, 2023) Manisha Nidhar; Vipin Kumar; Archisman Mahapatra; Priya Gupta; Priyanka Yadav; Priyanka Sonker; Akhilesh Kumar; Shweta Mishra; Rahul Kumar Singh; Ashish Kumar Tewari
This article describes studies on the design, synthesis, and biological evaluation of pyrazole-containing β-amino carbonyl compounds (5a–5q) as DPP-4 inhibitors and anti-diabetic agents. In contrast, mannich reactions went smoothly with bismuth nitrate (Bi (NO3)3) catalyst in the presence of ethanol and produced pyrazole-containing β-amino carbonyl compounds in good yield. Molecular docking studies of designed derivatives with DPP-4 enzyme (PDB: 2OLE), compounds 5d, 5h, 5j, and 5k showed excellent interaction. 3D QSAR and pharmacophoric model studies were also carried out. ADMET parameters, pharmacokinetic properties, and in vivo toxicity studies further confirmed that all the designed compounds were found to have good bioavailability and were less toxic. Further, these compounds were evaluated as enzyme-based in vitro DPP-4 inhibitory activity, and 5d, 5h, 5i, 5j, and 5k exhibited IC50 toward DPP-4 enzyme of 10.52, 10.41, 5.55, 4.16, and 7.5 nM, respectively. The most potent compound, 5j, was further selected for in vivo anti-diabetic activity using an STZ-induced diabetic mice model, and 5j showed a significant diabetic control effect. © 2022 John Wiley & Sons Ltd.
Ligand-based designing of DPP-4 inhibitors via hybridization; synthesis, docking, and biological evaluation of pyridazine-acetohydrazides
(Institute for Ionics, 2023) Manisha Nidhar; Vipin Kumar; Archisman Mahapatra; Priya Gupta; Brijesh Kumar Yadav; Rahul Kumar Singh; Ashish Kumar Tewari
Abstract: A series of novel pyridazine-acetohydrazide hybrids were designed, synthesized, and evaluated for their in vitro and in vivo antihyperglycemic activity. In this context, pyridazine-acetohydrazides (6a–6p) were synthesized by coupling substituted aldehyde with 2-(5-cyano-6-oxo-3,4-diphenylpyridazine-1-6H-yl) acetohydrazide, which was prepared via the reaction of pyridazine ester with hydrazine hydrate. The molecular docking study was carried out to examine the binding affinities and interaction of designed compounds against the DPP-4 enzyme. Compounds 6e, 6f, 6l, and 6n exhibited interaction with active residue. In silico ADMET properties, and toxicity studies corroborated that compounds were found to have good bioavailability and less toxic. The synthesized compounds were further estimated for in vitro DPP-4 activity. Compounds 6e and 6l were found as the most effective DPP-4 inhibitor in this series with IC50 values (6.48, 8.22 nM) when compared with sitagliptin (13.02 nM). According to the toxicity assay compound, 6l showed very less toxicity at a higher concentration so further selected for the in vivo antihyperglycemic activity. Graphical abstract: [Figure not available: see fulltext.]. © 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
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.
Preface
(Elsevier, 2025) Manisha Nidhar; Ashish Kumar Tewari
[No abstract available]
PTSA-induced synthesis, in silico and nano study of novel ethylquinolin–thiazolo–triazole in cervical cancer
(Taylor and Francis Ltd., 2024) Priyanka Sonker; Rupen Tamang; Abhishesh K Mehata; Manisha Nidhar; Vishal P Sharma; Vipin Kumar; Madaswamy S Muthu; Biplob Koch; Ashish K Tewari
Aim: p-Toluenesulfonic acid-(PTSA) and grinding-induced novel synthesis of ethylquinolin–thiazolo–triazole derivatives was performed using green chemistry. Materials & methods: Development of a nanoconjugate drug-delivery system of ethylquinolin–thiazolo–triazole was carried out with D-α-tocopheryl polyethylene glycol succinate (TPGS) and the formulation was further characterized by transmission electron microscopy, atomic force microscopy, dynamic light scattering and in vitro drug release assay. The effect of 3a nanoparticles was assessed against a cervical cancer cell line (HeLa) through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the effect on apoptosis was determined. Results & discussion: The 3a nanoparticles triggered the apoptotic mode of cell death after increasing the intracellular reactive oxygen level by enhancing cellular uptake of micelles. Furthermore, in silico studies revealed higher absorption, distribution, metabolism, elimination and toxicity properties and bioavailability of the enzyme tyrosine protein kinase. Conclusion: The 3a nanoparticles enhanced the therapeutic potential and have higher potential for targeted drug delivery against cervical cancer. © 2024 Expert Publishing Science Ltd trading as Taylor & Francis.
Quantitative intermolecular interactions analysis for amide-amide hydrogen-bonded synthons: Insilico studies for Cox-2 selective inhibitors
(Elsevier B.V., 2023) Akhilesh Kumar; Ranjeet Kumar; Rashmi Dubey; Manisha Nidhar; Indresh Verma; Praveen Singh; Ashish Kumar Tewari
Synthesis and characterization of diaryl fragment based pyridazine and triazine derivatives containing amide functional group have been carried out for the studies of amide-amide hydrogen-bonded synthons formation. The supramolecular synthons formations in solid state have been carried out by x-ray crystallography and Hirshfeld surface analysis. The crystal structure and Hirshfeld surface analysis have shown that synthons formation takes place by N-H⋯O interactions as well as some other interactions that stabilized the molecules. Further, insilico studies have been carried out for COX-2 selective Inhibitor. © 2023
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.