RESUMO
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.
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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.
Assuntos
Carboidratos , Descoberta de Drogas , Descoberta de Drogas/métodosRESUMO
Marine oil-spills have a long-lasting impact on the environment; therefore, it is a major concern in the scientific community to find a solution for remediation. Recently, phase selective organo-gelators emerged as potential materials for removal of oil from water through selective gelation. Herein, we report synthesis of a series of C-6 triazole linked N-acetylglucosamine derivatives, among which three have shown excellent selective gelation of organic solvents, diesel, petrol, and crude oils in water and seawater. We have studied phase selective gelation against different API grade crude oils (from light to heavy), and the gelation was achieved using nontoxic carrier solvent at room temperature in less than 15 min, and gelators were found useful for recovering crude oils. Critical gel concentration (CGC) of crude oil gelators was found to be 2.3-12% (w/v). The variable temperature NMR and FTIR experiments reveal that intermolecular hydrogen bonding was responsible for gel formation. Furthermore, a gelator was utilized for selective dye removal from water.
RESUMO
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.
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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.
Assuntos
Antineoplásicos , Cobre , Humanos , Triazóis/química , Pirimidinas/química , Relação Estrutura-Atividade , Células MCF-7 , Piranos , Catálise , Antineoplásicos/química , Estrutura Molecular , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
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.
RESUMO
The Ferrier rearrangement is a powerful tool to prepare 2,3-unsaturated glycopyranosides. We have reinvestigated SnCl4 catalyzed Ferrier rearrangements through direct allylic substitution of the hydroxyl group at the C-3 position of glycals, resulting in the formation of stereoselective 2,3-unsaturated glycosides at 0 °C. The catalytic amount of SnCl4 (0.1 equiv.) was successfully used to promote this transformation on 3,4,6-tri-O-acetyl-D-glucal, 3,4,6-tri-O-acetyl-D-galactal and 3,4-di-O-acetyl-D-arabinal using various nucleophiles viz alcohols, azide and thiols to form a variety of 2,3-unsaturated glycopyranosides (pseudoglycals). This straightforward process is notable for its strong anomeric selectivity, excellent yields and shorter reaction time.
Assuntos
Gluconato de Cálcio , Glicosídeos , CatáliseRESUMO
A metal free synthesis of enantiopure 2,3-dideoxy-α, ß-unsaturated carbohydrate enals (Perlin aldehydes), in CH3CN-0.02 N H2SO4 in water (1:1, v/v) with 0.5 equivalent additives (4-hydroxy-6-methyl-2-pyrone or 4-amino coumarin), has been reported. This efficient protocol works well for the acetylated glycals (glucal, galactal and arabinal) and afforded Perlin aldehydes and hemiacetals in acceptable to good yields. Whereas, benzylated glycals furnished respective Perlin aldehydes, hemiacetals and the 2-deoxy derivatives, under similar reaction conditions. The products yields were significantly reduced when the additives were removed from the reaction mixture, indicating that they constitute an essential component of this approach. Further the use of 0.02 N H2SO4 in water: acetonitrile (1:1, v/v) solvent system is essential for the formation of Perlin aldehydes. The similar reactions under neutral reaction conditions (CH3CN:H2O, 1:1, v/v) with additives, afforded the hemiacetals as major product. This methodology is a metal free approach to Perlin aldehyde synthesis and therefore having additional benefit of its use in preparation of bioactive drug molecules, where metal toxicity is the major concern.