Browsing by Author "Vinay Kumar Mishra"

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Base-Induced Annulation of Glycal-Derived α-iodopyranone with 2-Aminopyrimidinones: Access to Chiral Imidazopyrimidinones
(John Wiley and Sons Inc, 2024) Vinay Kumar Mishra; Ghanshyam Tiwari; Ashish Khanna; Yogesh Yadav; Ram Sagar
A simple, environmentally benign and catalyst-free method for the synthesis of chirally enriched imidazo[1,2-a]pyrimidinone glycohybrids has been successfully developed. The protocol is based on a base-induced annulation of α-iodo-pyranone with Michael addition of 2-aminopyrimidinones followed by intramolecular nucleophilic substitution reaction. The privilege of this method includes mild reaction conditions, eco-friendly solvent and a transition-metal-free approach. Moreover, using straightforward simple methods, this reaction method exhibits a broad range of substrate scope and remarkable tolerance toward various functional groups. © 2024 Wiley-VCH GmbH.
Cardenolide and pregnatriene compounds from the roots of Nerium oleander
(Taylor and Francis Ltd., 2021) Vinay Kumar Mishra; Braj Kishore Rathour; Sunil K. Mishra; Ram Sagar
Cardenolide and pregnatriene compounds were isolated from the chloroform fraction of the 95% aqueous ethanolic extract of dried roots of Nerium oleander. The stereochemical structure of the cardenolide and pregnatriene compounds was determined to be 3β-O-(D-diginosyl)-14β-hydroxy card-20(22)-enolide and 12β-hydroxy pregna-4,6,16-triene-3,20-dione using spectroscopic methods including IR, HRMS and NMR spectroscopy. © 2020 Informa UK Limited, trading as Taylor & Francis Group.
Copper-catalyzed synthesis of pyrazolo[1,5-a]pyrimidine based triazole-linked glycohybrids: mechanistic insights and bio-applications
(Nature Research, 2024) Ghanshyam Tiwari; Ashish Khanna; Rajdeep Tyagi; Vinay Kumar Mishra; Chintam Narayana; Ram Sagar
Hybrid molecules maintain their stronghold in the drug market, with over 60% of drug candidates in pharmaceutical industries. The substantial expenses for developing and producing biologically privileged drugs are expected to create opportunities for producing hybrid molecule-based drugs. Therefore, we have developed a simple and efficient copper-catalyzed approach for synthesizing a wide range of triazole-linked glycohybrids derived from pyrazolo[1,5-a]pyrimidines. Employing a microwave-assisted copper-catalyzed approach, we developed a concise route using various 7-O-propargylated pyrazolo[1,5-a]pyrimidines and 1-azidoglycosides. This strategy afforded a series of twenty-seven glycohybrids up to 98% yield with diverse stereochemistry. All were achieved within a remarkably shortened time frame. Our investigation extends to evaluating the anticancer potential of these synthesized triazole-linked pyrazolo[1,5-a] pyrimidine-based glycohybrids. In-vitro assays against MCF-7, MDA-MB231, and MDA-MB453 cell lines reveal intriguing findings. (2R,3S,4S,5R,6R)-2-(acetoxymethyl)-6-(4-(((5-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate emerges as a standout with better anticancer activity against MDA-MB231 cells (IC50 = 29.1 µM), while (2R,3R,4S,5R,6R)-2-(acetoxymethyl)-6-(4-(((5-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate demonstrates the best inhibitory effects against MCF-7 cells (IC50 = 15.3 µM) in all derived compounds. These results align with our docking analysis and structure–activity relationship (SAR) investigations, further validating the in-vitro outcomes. This work not only underscores the synthetic utility of our devised protocol but also highlights the promising potential of these glycohybrids as candidates for further anticancer therapeutic exploration. © 2024, The Author(s).
Efficient Synthesis of Chirally Enriched 1 H -Imidazo[1,2- b ]pyrazole- and 4 H -Imidazo[1,2- b ][1,2,4]triazole-Based Bioactive Glycohybrids
(Georg Thieme Verlag, 2023) Vinay Kumar Mishra; Ghanshyam Tiwari; Ashish Khanna; Rajdeep Tyagi; Ram Sagar
Carbohydrates, traditionally known for their energy-providing role, have gained significant attention in drug discovery due to their diverse bioactivities and stereodiversity. However, pure carbohydrate molecules often exhibit limited bioactivity and suboptimal chemical and physical characteristics. To address these challenges, bioactive scaffolds have been incorporated into carbohydrate to enhance their bioactivity and improve their overall properties. Among the various heterocyclic structural motifs known for their pharmacological properties, imidazo-pyrazole and imidazo-triazole skeleton have gained larger attention among synthetic and medicinal chemists as they possess good biological and pharmacological properties. The incorporation of these bioactive scaffolds with carbohydrates adopting developed efficient synthetic protocol to synthesize new class of imidazo-pyrazole and imidazo-triazole glycohybrid molecules is reported. The carbohydratederived ?-iodo-2,3-dihydro-4H-pyran-4-ones have been identified as suitable precursors, which were coupled with various aminopyrazoles and aminotriazoles to obtain designed glycohybrids. Thus, various imidazo-pyrazole and imidazo-triazole based glycohybrids have been prepared efficiently in good to excellent yields. These new glycohybrids were evaluated for their anticancer activity and selected compounds were found to possess submicromolar anticancer activity against MCF-7 breast cancer cell line. These molecules could potentially be developed as new chemical entities in pharmaceutical chemistry and may encourage the use of carbohydrates in stereo-divergent synthesis and drug discovery processes. © 2023 Georg Thieme Verlag. All rights reserved.
Efficient Synthesis of Natural Product Inspired Naphthoquinone-Fused Glycohybrids and Their in Silico Docking Studies
(Georg Thieme Verlag, 2023) Ashish Khanna; Ghanshyam Tiwari; Vinay Kumar Mishra; Kavita Singh; Ram Sagar
Naphthoquinones, a diverse group of natural compounds with a 1,4-naphthoquinone core structure, have gained attention for their pharmacological properties. The anticancer activity of these compounds is attributed to their ability to accept electrons, leading to the generation of reactive oxygen species that cause DNA damage and cell death. In recent studies, hydroxy-1,4-naphthoquinone derivatives, including daunorubicin, have shown promising inhibitory effects against several human cancers, such as acute myeloid leukemia, chronic myelogenous leukemia, and Kaposi s sarcoma. To further explore their potential as anticancer agents, this research article focuses on the design and synthesis of natural product inspired naphthoquinone-based glycohybrids. These glycohybrids are designed based on the structures of bioactive aryl glycosides and quinones, aiming to enhance their binding affinity and specificity towards cancer-related protein targets. The interactions between the synthesized glycohybrids and target proteins through computational docking simulations has been studied and better binding affinity was found. © 2023 Georg Thieme Verlag. All rights reserved.
Estimation of Stature from Foot Length in Eastern Uttar Pradesh: A Prospective Cross-Sectional Study
(Punjab Academy of Forensic Medicine and Toxicology, 2025) Vinay Kumar Mishra; Deepan Roy; Surendra Kumar Pandey
Introduction: Stature estimation significantly contributes to forensic anthropology, particularly when complete skeletal remains are unavailable. Foot length, frequently preserved even in fragmented remains, has emerged as a dependable anthropometric measure for stature prediction, yet specific data for the Eastern Uttar Pradesh population in India are limited. This prospective observational study, conducted from April 2023 to September 2024 in Varanasi, aimed to assess the correlation between foot length and height and to establish regression models for accurate stature estimation. A total of 500 healthy adult volunteers (250 males, 250 females), aged between 25 to 55 years, participated, providing measurements of stature using an anthropometric rod and bilateral foot lengths via spreading calipers. Analysis using SPSS version 25.0 indicated a mean stature of 160.99 ± 9.81 cm, with males significantly taller (168.06 ± 7.21 cm) compared to females (153.92 ± 6.37 cm, p < 0.0001). Mean foot lengths were 24.21 ± 1.70 cm (right) and 24.25 ± 1.70 cm (left), both strongly correlated with stature (right foot r = 0.85, left foot r = 0.86, p < 0.0001). Derived linear regression equations demonstrated stature predictions: 4.9408 × right foot length + 41.388, and 4.9818 × left foot length + 40.239. Multivariate regression models incorporating variables such as age, gender, religion, and education further enhanced predictive accuracy (R = 0.898–0.899). A slightly stronger correlation with the left foot suggests minimal bilateral asymmetry. Observed sexual dimorphism, with males having greater stature and longer feet, aligns with global indings. Females exhibited lower correlations (r = 0.63–0.66), re lecting greater anthropometric variability potentially in luenced by hormonal and morphological differences. Age-related stature decline beyond 40 years and the positive link between stature and educational status highlight physiological and socioeconomic in luences. Despite limitations, including convenience sampling and exclusion of younger populations, this study underscores the importance of population-specific anthropometric equations in forensic identification. © 2025, Punjab Academy of Forensic Medicine and Toxicology. All rights reserved.
Genetic diversity in Indian cucumber based on microsatellite and morphological markers
(2013) Sudhakar Pandey; Waquar Akhter Ansari; Vinay Kumar Mishra; Asheesh Kumar Singh; Major Singh
Genetic variation among 44 cucumber accessions was assessed using morphological and SSR markers. High genetic variability was observed for days to 50% female flowering (37-46 days from sowing), number of fruits per plant (1.4-6.0), individual fruit weight (0.04-0.552kg) and root length (14.25-32.8cm). The pair-wise Jaccard similarity coefficient ranged between 0.25 and 0.85 indicating that the accessions represent genetically diverse populations. The allelic diversity of polymorphic markers ranged from 0.001 to 0.9396 with an average of 0.31 based on polymorphic information content. The clustering pattern of SSR markers was not in consonance with the groupings based on quantitative traits. The accession of Indian state i.e.; Madhya Pradesh and Uttar Pradesh were diverged from the accessions of other parts of India. The study provides information for future exploration and collection of cucumber germplasm in India and utilization of diverse germplasm for developing cultivars/hybrids for specific traits. © 2013 Elsevier Ltd.
Microwave-Assisted Copper-Catalyzed Synthesis of Triazole-linked 2-Amino-Pyrimidinone based Glycohybrids
(John Wiley and Sons Inc, 2024) Vinay Kumar Mishra; Ashish Khanna; Ghanshyam Tiwari; Yogesh Yadav; Ram Sagar
2-Amino pyrimidines are vital molecules that exhibit diverse biological activities and serve as structural motifs in various pharmaceutical drugs. Four new series of triazole-linked glycohybrids of 2-amino-pyrimidinones were designed and efficiently synthesized, using a microwave-assisted method under click chemistry reaction conditions. The N-propargyl-2-aminopyrimidinone and O-propargyl-2-aminopyrimidine derivatives successfully underwent the click reactions with 1-azido-tetra-O-acetyl-β-D-glucose, D-galactose and D-mannose. In this work, we reported the series of novel thirty-three new triazole-linked glycohybrid molecules with stereochemical diversity and diverse substitution patterns. © 2024 Wiley-VCH GmbH.
Molecular Design, Synthesis and Anti-cancer Activity of Novel Pyrazolo[3,4-b]pyridine-based Glycohybrid Molecules
(Academic Press Inc., 2025) Neetu Verma; Ghanshyam Tiwari; Ashish Khanna; Vinay Kumar Mishra; Yogesh Jawaharlal Yadav; Manisha Malviya; Ram Sagar
Molecular hybridization is an emerging strategy in medicinal chemistry for designing new bioactive molecules that link pharmacophores covalently and shows synergistic enhanced properties. Herein, we have developed pyrazolo[3,4-b]pyridine-based new glycohybrids considering the Warburg effect. A microwave-assisted, copper-catalyzed efficient synthesis of new triazole-linked glycohybrids based on pyrazolo[3,4-b]pyridines scaffold was achieved successfully in high yields with inherent stereochemical diversity from D-glucose, D-galactose, and D-mannose. The twenty-three distinct new glycohybrids, incorporating various electron-donating and electron-withdrawing groups with stereochemical diversities, were prepared using developed synthetic protocol. This efficient synthesis significantly reduced reaction time and furnished products with high isolated yields, showcasing its potential for glycohybrids synthesis. In-vitro study revealed that among the synthesized glycohybrids, compound 8e emerged as a potential compound against MDA-MB231 (SI > 31) and MCF-7 (SI > 434) with an IC50 value of 19.58 µM and 1.42 µM respectively. The molecular docking study predicts the binding interaction of the chemical probe with the target protein HCK. The enzyme inhibition assay revealed that compound 8e is having strong inhibitory potency against HCK enzyme. This article highlights the synthetic utility of this strategy and the potential applications of these newly designed and prepared glycohybrids. © 2025 Elsevier Inc.
Recent advances in synthesis of diverse glycopeptides and glycohybrids
(Elsevier, 2023) Rajdeep Tyagi; Kavita Singh; Vinay Kumar Mishra; Ram Sagar
Glycopeptides and glycohybrids are an important class of molecules due to their potential of being used as a drug for the treatment of several human diseases. They also play a very important role in cell-cell communication, host-pathogen interactions, cell division, and so on and therefore are considered molecules of interest in the chemical biology and medicinal chemistry community. Therefore much attention has been paid by the scientific community to the development of new synthetic routes to construct diverse glycopeptides. In glycopeptides, the glycan part is linked to the amino acid residue of a protein or peptide as Asn/Arg/Lys for N-linked glycopeptides, Ser/Thr/HyPro/HyLys/Tyr for O-linked glycopeptides, and Cys or its derivatives for S-linked glycopeptides. Whereas in glycohybrids, glycan parts can be merged, fused, or linked with privileged drug-like molecules. Glycopeptides and glycohybrids are important sources of templates for the design and development of drug candidates but their natural occurrence is limited. Therefore the development of new synthetic methods is needed to prepare a diverse class of glycopeptides and glycohybrids, which is a challenge for the researchers due to the presence of multiple reaction sites and stereo diversity in carbohydrate molecules. Continuous efforts were being made by synthetic communities around the globe to construct such molecules efficiently and stereoselectively in larger quantities. This chapter comprises the recent developments in the chemical synthesis of glycopeptides in solution, automated, and/or solid-phase and glycohybrids. © 2023 Elsevier Inc. All rights reserved.
Recent Advances in the Synthesis of Bioactive Glycohybrids via Click-Chemistry
(Georg Thieme Verlag, 2023) Kavita Singh; Rajdeep Tyagi; Vinay Kumar Mishra; Ghanshyam Tiwari; Ram Sagar
Carbohydrates, traditionally known for their energy-providing role, have gained significant attention in drug discovery due to their diverse bioactivities and stereodiversity. However, pure carbohydrate molecules often exhibit limited bioactivity and suboptimal chemical and physical characteristics. To address these challenges, functional groups with bioactive scaffolds have been incorporated into carbohydrate to enhance their bioactivity and improve their overall properties. Among the various synthetic methods available, click chemistry has emerged as a powerful tool for the synthesis of carbohydrate-containing bioactive scaffolds, known as glycohybrids. Click chemistry offers several advantages, including high chemo- and regioselectivity, mild reaction conditions, easy purification, and compatibility with multiple functional groups. In the present review, we have emphasized the recent advances and most pertinent research on the development of 1,2,3-triazole-containing glycohybrids using the click reaction, their biological evaluations and the structure-activity relationship during 2017-2023. These newly synthesised glycohybrids could potentially be developed as new chemical entities (NCE) in pharmaceutical chemistry and may encourage the use of carbohydrates in drug discovery processes. © 2023. The Author(s).
Recent developments on microwave-assisted organic synthesis of nitrogen- and oxygen-containing preferred heterocyclic scaffolds
(Royal Society of Chemistry, 2023) Ghanshyam Tiwari; Ashish Khanna; Vinay Kumar Mishra; Ram Sagar
In recent decades, the utilization of microwave energy has experienced an extraordinary surge, leading to the introduction of innovative and revolutionary applications across various fields of chemistry such as medicinal chemistry, materials science, organic synthesis and heterocyclic chemistry. Herein, we provide a comprehensive literature review on the microwave-assisted organic synthesis of selected heterocycles. We highlight the use of microwave irradiation as an effective method for constructing a diverse range of molecules with high yield and selectivity. We also emphasize the impact of microwave irradiation on the efficient synthesis of N- and O-containing heterocycles that possess bioactive properties, such as anti-cancer, anti-proliferative, and anti-tumor activities. Specific attention is given to the efficient synthesis of pyrazolopyrimidines-, coumarin-, quinoline-, and isatin-based scaffolds, which have been extensively studied for their potential in drug discovery. The article provides valuable insights into the recent synthetic protocols and trends for the development of new drugs using heterocyclic molecules. © 2023 The Royal Society of Chemistry.
Recent developments on the synthesis of biologically active glycohybrids
(Academic Press Inc., 2024) Vinay Kumar Mishra; Ashish Khanna; Ghanshyam Tiwari; Rajdeep Tyagi; Ram Sagar
The exploration of hybridization emerges as a potent tool in advancing drug discovery research, with a significant emphasis on carbohydrate-containing hybrid scaffolds. Evidence indicates that linking carbohydrate molecules to privileged bioactive scaffolds enhances the bioactivity of drug molecules. This synergy results in a diverse range of activities, making carbohydrate scaffolds pivotal for synthesizing compound libraries with significant functional and structural diversity. Beyond their synthesis utility, these scaffolds offer applications in screening bioactive molecules, presenting alternative avenues for drug development. This comprehensive review spanning 2015 to 2023 focuses on synthesized glycohybrid molecules, revealing their bioactivity in areas such as anti-microbial, anti-cancer, anti-diabetic, anti-inflammatory activities, enzyme inhibition and pesticides. Numerous novel glycohybrids surpass positive control drugs in biological activity. This focused study not only highlights the diverse bioactivities of glycohybrids but also underscores their promising role in innovative drug development strategies. © 2024 Elsevier Inc.
Recent Efforts in Identification of Privileged Scaffolds as Antiviral Agents
(John Wiley and Sons Inc, 2023) Yogesh Yadav; Kavita Singh; Sunil Sharma; Vinay Kumar Mishra; Ram Sagar
Viral infections are the most important health concern nowadays to mankind, which is unexpectedly increasing the health complications and fatality rate worldwide. The recent viral infection outbreak developed a pressing need for small molecules that can be quickly deployed for the control/treatment of re-emerging or new emerging viral infections. Numerous viruses, including the human immunodeficiency virus (HIV), hepatitis, influenza, SARS-CoV-1, SARS-CoV-2, and others, are still challenging due to emerging resistance to known drugs. Therefore, there is always a need to search for new antiviral small molecules that can combat viral infection with new modes of action. This review highlighted recent progress in developing new antiviral molecules based on natural product-inspired scaffolds. Herein, the structure-activity relationship of the FDA-approved drugs along with the molecular docking studies of selected compounds have been discussed against several target proteins. The findings of new small molecules as neuraminidase inhibitors, other than known drug scaffolds, Anti-HIV and SARS-CoV are incorporated in this review paper. © 2023 Wiley-VHCA AG, Zurich, Switzerland.
Synthesis of Chirally Enriched Pyrazolylpyrimidinone-Based Glycohybrids via Annulation of Glycals with 2-Hydrazineylpyrimidin-4(3H)-ones
(American Chemical Society, 2024) Ghanshyam Tiwari; Vinay Kumar Mishra; Ashish Khanna; Rajdeep Tyagi; Ram Sagar
A new strategy for synthesizing chirally enriched pyrazolylpyrimidinone-based glycohybrids has been achieved, employing an annulation approach in ethanol without any additives or catalysts under microwave conditions. The designed compounds were obtained within a short reaction time (5 min). This method offers several advantages, including mild reaction conditions, a green solvent, and a metal-free approach. Furthermore, the protocol demonstrated a broad substrate scope, successfully incorporating various functional groups with stereochemical diversity and furnishing chirally enriched molecules. © 2024 American Chemical Society.
Synthesis of triazole bridged N-glycosides of pyrazolo[1,5-a]pyrimidinones as anticancer agents and their in silico docking studies
(Royal Society of Chemistry, 2024) Ghanshyam Tiwari; Vinay Kumar Mishra; Priti Kumari; Ashish Khanna; Sunil Sharma; Ram Sagar
In the pursuit of novel therapeutic agents, we present a comprehensive study on the design, synthesis, and evaluation of a diverse library of triazole bridged N-glycosides of pyrazolo[1,5-a]pyrimidinones, employing a microwave-assisted synthetic approach via ‘click chemistry’. This methodology offers efficient and accelerated access to the glycohybrids, showcasing improved reaction conditions that yield high-quality products. In this research endeavor, we have successfully synthesized a series of twenty-seven triazole bridged N-glycosides of pyrazolo[1,5-a]pyrimidinones. Our investigation extends beyond synthetic endeavors to explore the potential therapeutic relevance of these compounds. We subjected them to rigorous in vitro screening against prominent breast cancer cell lines MCF-7, MDA-MB231, and MDA-MB453. Among the library of compounds synthesized, (2S,3S,4R,5S,6S)-2-(acetoxymethyl)-6-(4-((5-(4-methoxyphenyl)-7-oxopyrazolo[1,5-a]pyrimidin-1(7H)-yl)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate emerged as a potent compound, exhibiting remarkable anti-cancer activity with an IC50 value of 27.66 μM against the MDA-MB231 cell line. Additionally, (2S,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(4-((7-oxo-5-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyrimidin-1(7H)-yl)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate displayed notable inhibitory potential against the MCF-7 cell line, with an IC50 value of 4.93 μM. Furthermore, in silico docking analysis was performed to validate our experimental findings. These findings underscore the promise of our triazole bridged N-glycosides of pyrazolo[1,5-a]pyrimidinones as potential anti-cancer agents. This research not only enriches the field of glycohybrid synthesis but also contributes valuable insights into the development of novel anti-cancer therapeutics. © 2024 The Royal Society of Chemistry.