Browsing by Author "Ashish Khanna"

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A small bioactive glycoside inhibits epsilon toxin and prevents cell death
(Company of Biologists Ltd, 2019) Abhishek Shivappagowdar; Soumya Pati; Chintam Narayana; Rajagopal Ayana; Himani Kaushik; Raj Sah; Swati Garg; Ashish Khanna; Jyoti Kumari; Lalit Garg; Ram Sagar; Shailja Singh
Clostridium perfringens epsilon toxin (Etx) is categorized as the third most lethal bioterrorism agent by the Centers for Disease Control and Prevention (CDC), with no therapeutic counter measures available for humans. Here, we have developed a high-affinity inhibitory compound by synthesizing and evaluating the structure activity relationship (SAR) of a library of diverse glycosides (numbered 1-12). SAR of glycoside-Etx heptamers revealed exceptionally strong H-bond interactions of glycoside-4 with a druggable pocket in the oligomerization and β-hairpin region of Etx. Analysis of its structure suggested that glycoside-4 might self-aggregate to form a robust micelle-like supra-molecular complex due to its linear side-chain architecture, which was authenticated by fluorescence spectroscopy. Further, this micelle hinders the Etx monomer-monomer interaction required for oligomerization, validated by both surface plasmon resonance (SPR) and immunoblotting. This phenomenon in turn leads to blockage of pore formation. Downstream evaluation revealed that glycoside-4 effectively blocked cell death of Etx-treated cultured primary cells and maintained cellular homeostasis via disrupting oligomerization, blocking pore formation, restoring calcium homeostasis, stabilizing the mitochondrial membrane and impairing high mobility group box 1 (HMGB1) translocation from nucleus to cytoplasm. Furthermore, a single dosage of glycoside-4 protected the Etx-challenged mice and restored normal function to multiple organs. This work reports for the first time a potent, nontoxic glycoside with strong ability to occlude toxin lethality, representing it as a bio-arm therapeutic against Etx-based biological threat. © 2019. Published by The Company of Biologists Ltd
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.
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).
Design and efficient synthesis of pyrazoline and isoxazole bridged indole C-glycoside hybrids as potential anticancer agents
(Nature Research, 2020) Priti Kumari; Vishnu S. Mishra; Chintam Narayana; Ashish Khanna; Anindita Chakrabarty; Ram Sagar
C-glycosides are important class of molecules exhibit diverse biological activities and present as structural motif in many natural products. Two series of new pyrazoline and isoxazole bridged indole C-glycoside molecular hybrids (n = 36) were efficiently synthesized starting from diverse indole 3-carboxaldehydes derived α, β-unsaturated ketone derivatives of β-D-glucosyl-propan-2-one, β-D-galactosyl-propan-2-one and β-D-mannosyl-propan-2-one, reacting with hydrazine hydrate and hydroxyl amine hydrochloride in shorter reaction time (15 min) under microwave assisted condition. Anticancer activity of these newly synthesized pyrazoline and isoxazole bridged indoles C-glycoside hybrids were determined in details through cellular assays against MCF-7, MDA-MB-453 and MDA-MB-231 cancer cell lines. The selected library members displayed low micromolar (IC50 = 0.67–4.67 µM) and selective toxicity against breast cancer cell line (MCF-7). Whereas these compounds were nontoxic towards normal cell line (MCF-10A). Mechanistic studies showed that, active compounds inhibit COX-2 enzyme, which was also supported by molecular docking studies. These findings are expected to provide new leads towards anticancer drug discovery. © 2020, The Author(s).
Efficient synthesis and in-silico studies of pyrano[3,2-c]pyrones based glycohybrids
(Elsevier B.V., 2024) Kanchan Yadav; Ashish Khanna; Rajdeep Tyagi; Sunil Sharma; Ram Sagar
This work is comprising of designing, efficient synthesis and molecular docking studies of pyrano[3,2-c]pyrones based stereodivergent glycohybrids. The diverse pyrano[3,2-c]pyrones based glycohybrids were efficiently prepared through condensation of 4-hydroxycoumarin derivatives and 4‑hydroxy-6-methyl-2H-pyran-2-ones with various enantiopure 2,3-dideoxy-α,β-unsaturated carbohydrate enals using organo-catalyst, L-proline, in EtOAc at room temperature. 3,4,6-tri-O-acetyl-D-glucal derived acetyl-protected carbohydrate enals yielded highly diastereoselective glycohybrid products. Whereas, poor selectivity was observed with α,β-unsaturated carbohydrate enals obtained from 3,4,6-tri-O-acetyl-D-galactal. The in-silico investigations show the significant binding activity of the selected compounds in the active binding site of HCK protein (PDB: 1QCF) with the better docking score of −7.13 kcal/mol as compared to the co-crystallized ligand PP1 (−6.77 kcal/mol). Additionally, MM/GBSA was calculated using the Prime module to determine the binding energy of the ligands. Selected compounds showed the maximum binding affinity of −74.18 kcal/mol compared to the co-crystallized ligand PP1 (−70.40 kcal/mol). ADMET screening of these compounds predicts the low toxicity and better metabolic profile of the synthesized compounds inside the body. © 2024 Elsevier B.V.
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 indole-chalcones based glycohybrids and their anticancer activity
(Elsevier Ltd, 2024) Rajdeep Tyagi; Kanchan Yadav; Ashish Khanna; Sunil K. Mishra; Ram Sagar
Indole based glycosides belong to the class of pharmacologically active molecules and found in diverse natural compounds. Herein, we report the synthesis of 1,2,3-triazole bridged chirally enriched diverse indole-chalcones based glycohybrids. Three series of glycohybrids were designed and efficiently synthesized using D-glucose, D-galactose and D-mannose derived 1-azido glycosides. The reactions sequence involved were, the synthesis of indole derived chalcones which were formed via Claisen–Schmidt condensation reaction and subsequently N-propargylation which leads to the production of N-propargylated indole-chalcones. The N-propargylated indole-chalcones get transformed into 1,2,3-triazole bridged indole-chalcone based glycohybrids by reacting with 1-azido sugar glycosides under click-chemistry reaction conditions. Further, the biological activity of synthesized glycohybrids (n = 27) was assessed in-vitro against MDA-MB231, MCF-7, MDA-MB453 cancer, and MCF-10A normal cell lines. The selected compounds showed potent anti-oncogenic properties against MCF-7 and MDA-MB231 breast cancer cell line with IC50 values of 1.05 µM and 11.40 µM respectively, with very good selectivity index (SI > 161). The active compounds show better binding affinity as compared to co-crystallized inhibitor 1-(tert-butyl)-3-(p-tolyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (PP1) with HCK (PTKs) proteins in molecular docking studies. © 2024 Elsevier Ltd
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.
Electro-organic synthesis of isatins and hydrazones through C-N cross-coupling and C(sp2)-H/C(sp3)-H functionalization
(Royal Society of Chemistry, 2023) Neetu Verma; Rajdeep Tyagi; Ashish Khanna; Manisha Malviya; Ram Sagar
An efficient and unique approach to synthesize isatin (indole-2,3-dione) from 2-aminoacetophenone under electrochemical conditions supported by I2-DMSO through C-N cross-coupling and C(sp2)-H/C(sp3)-H functionalization is presented. This synthetic method spans a wide range of substituted 2-aminoacetophenone substrates. The use of iodine as a promoter and shorter reaction times produced good to very good yields of isatin derivatives, which is a significant improvement over the reaction in a batch process. Further, hydrazones of isatin were synthesized by using hydrazine hydrate which produces electrochemically active molecules, namely isatin-hydrazones. The hydrazones of acetophenone were also obtained using the same reaction protocol. Additionally, the effect of increasing scan rate studied using cyclic voltammetry shows that the process followed a diffusion-controlled mechanism. © 2023 The Royal Society of Chemistry.
Exploiting Microwave-Assisted Organic Synthesis (MAOS) for Accessing Bioactive Scaffolds
(Bentham Science Publishers, 2021) Ashish Khanna; Prashant Dubey; Ram Sagar
A microwave-assisted organic synthesis is an alternative approach towards the traditional way of heating to obtain desired bioactive scaffolds as a product. This method has transformed the approaches of organic synthesis, due to shorter reaction time with high product yields, modifications of selectivity, increased product purities, and simplification of workup procedures. The microwave-assisted reactions can be performed under solvent-free conditions. Thus, Microwave-Assisted Organic Synthesis (MAOS) has become the first choice for the medicinal chemist and chemical biologist to use as a tool to perform organic reactions in drug discovery and medicinal chemistry. Microwave-assisted organic synthesis specifically results in the desired products with higher selectivity and purity which may have better pharmacological properties. In this review article, we covered the literature from 2010-till to date, focusing on the use of microwave irradiation in performing organic reactions to deliver various bioactive scaffolds. © 2021 Bentham Science Publishers.
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.
Pathogen induced subversion of NAD+ metabolism mediating host cell death: a target for development of chemotherapeutics
(Springer Nature, 2021) Ayushi Chaurasiya; Swati Garg; Ashish Khanna; Chintam Narayana; Ved Prakash Dwivedi; Nishant Joshi; Zill e Anam; Niharika Singh; Jhalak Singhal; Shikha Kaushik; Amandeep Kaur Kahlon; Pallavi Srivastava; Manisha Marothia; Mukesh Kumar; Santosh Kumar; Geeta Kumari; Akshay Munjal; Sonal Gupta; Preeti Singh; Soumya Pati; Gobardhan Das; Ram Sagar; Anand Ranganathan; Shailja Singh
Hijacking of host metabolic status by a pathogen for its regulated dissemination from the host is prerequisite for the propagation of infection. M. tuberculosis secretes an NAD+-glycohydrolase, TNT, to induce host necroptosis by hydrolyzing Nicotinamide adenine dinucleotide (NAD+). Herein, we expressed TNT in macrophages and erythrocytes; the host cells for M. tuberculosis and the malaria parasite respectively, and found that it reduced the NAD+ levels and thereby induced necroptosis and eryptosis resulting in premature dissemination of pathogen. Targeting TNT in M. tuberculosis or induced eryptosis in malaria parasite interferes with pathogen dissemination and reduction in the propagation of infection. Building upon our discovery that inhibition of pathogen-mediated host NAD+ modulation is a way forward for regulation of infection, we synthesized and screened some novel compounds that showed inhibition of NAD+-glycohydrolase activity and pathogen infection in the nanomolar range. Overall this study highlights the fundamental importance of pathogen-mediated modulation of host NAD+ homeostasis for its infection propagation and novel inhibitors as leads for host-targeted therapeutics. © 2021, The Author(s).
Publisher Correction: Design and efficient synthesis of pyrazoline and isoxazole bridged indole C-glycoside hybrids as potential anticancer agents (Scientific Reports, (2020), 10, 1, (6660), 10.1038/s41598-020-63377-x)
(Nature Research, 2020) Priti Kumari; Vishnu S. Mishra; Chintam Narayana; Ashish Khanna; Anindita Chakrabarty; Ram Sagar
This Article contains an incorrect version of Scheme 1 and Scheme 2. The correct version of Scheme 1 and Scheme 2 appears below. © 2020, The Author(s).
Recent Advances in the Synthesis of 2-Hydroxy-1,4-naphthoquinone (Lawsone) Derivatives
(Georg Thieme Verlag, 2023) Ram Sagar; Uma Shankar; Ashish Khanna; Kavita Singh; Ghanshyam Tiwari
Lawsone, also known as 2-hydroxy-1,4-naphthoquinone, has been extensively studied and found to be a crucial precursor in the production of a diverse range of natural products such as molecular scaffolds, which are highly sought-after for biological research purposes. Due to its unique chemical composition, lawsone has been utilized for over a century as a starting material for the synthesis of numerous biologically active molecules and materials, and its intriguing properties have been showcased across a wide range of scientific and technological applications. Additionally, the various characteristics of lawsone have been widely used in organic synthesis processes. Recent advances in the synthesis of different scaffolds starting from lawsone, and their applications, are discussed in detail in the current review covering the period 2017 to 2023. 1 Introduction 2 Synthetic Developments on 2-hydroxy-1,4-naphthoquinone 3 Conclusions. © 2022. 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.
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.
Total Syntheses of Kirkamide and N-acetyl ent-Conduramine B-1
(Wiley-VCH Verlag, 2021) Chintam Narayana; Ashish Khanna; Priti Kumari; Ram Sagar
The second total synthesis of recently isolated new C7N aminocyclitol, kirkamide, has been developed. The enantiopure epoxide derived from N-acetylglucosamine in few steps was used as a synthon to accomplish the metal free synthesis of kirkamide and N-acetyl ent-conduramine B-1 in gram scale. The key synthetic steps involve stereoselective epoxidation, acid mediated regioselective epoxide ring opening followed by selective olefination. © 2020 Wiley-VCH GmbH