Browsing by Author "Priti Kumari"

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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).
Design and synthesis of N–acetylglucosamine derived 5a-carbasugar analogues as glycosidase inhibitors
(Elsevier Ltd, 2018) Chintam Narayana; Priti Kumari; Daisuke Ide; Nasako Hoshino; Atsushi Kato; Ram Sagar
An efficient synthesis of new six-membered carbasugars in both L-form and D-form starting from N–acetylglucosamine is described. The key synthetic steps involved regioselective protection and deprotection, Ferrier carbocyclization, Peterson olefination, hydroboration and stereoselective epoxidation followed by regioselective epoxide ring opening reactions. These six-membered carbasugars showed moderate glycosidase inhibitory activity and one of the compounds was found selective towards β-galactosidase inhibitory activity. © 2018 Elsevier Ltd
Enhanced uptake, high selective and microtubule disrupting activity of carbohydrate fused pyrano-pyranones derived from natural coumarins attributes to its anti-malarial potential
(BioMed Central, 2019) Sonal Gupta; Juveria Khan; Priti Kumari; Chintam Narayana; R. Ayana; Malabika Chakrabarti; Ram Sagar; Shailja Singh
Background: Malaria is one of the deadliest infectious diseases caused by protozoan parasite of Plasmodium spp. Increasing resistance to anti-malarials has become global threat in control of the disease and demands for novel anti-malarial interventions. Naturally-occurring coumarins, which belong to a class of benzo-α-pyrones, found in higher plants and some essential oils, exhibit therapeutic potential against various diseases. However, their limited uptake and non-specificity has restricted their wide spread use as potential drug candidates. Methods: Two series of carbohydrate fused pyrano[3,2-c]pyranone carbohybrids which were synthesized by combination of 2-C-formyl galactal and 2-C-formyl glucal, with various freshly prepared 4-hydroxycoumarins were screened against Plasmodium falciparum. The anti-malarial activity of these carbohybrids was determined by growth inhibition assay on P. falciparum 3D7 strain using SYBR green based fluorescence assay. Haemolytic activity of carbohybrid 12, which showed maximal anti-malarial activity, was determined by haemocompatibility assay. The uptake of the carbohybrid 12 by parasitized erythrocytes was determined using confocal microscopy. Growth progression assays were performed to determine the stage specific effect of carbohybrid 12 treatment on Pf3D7. In silico studies were conducted to explore the mechanism of action of carbohybrid 12 on parasite microtubule dynamics. These findings were further validated by immunofluorescence assay and drug combination assay. Results: 2-C-formyl galactal fused pyrano[3,2-c]pyranone carbohybrid 12 exhibited maximum growth inhibitory potential against Plasmodium with IC50 value of 5.861 μM and no toxicity on HepG2 cells as well as no haemolysis of erythrocytes. An enhanced uptake of this carbohybrid compound was observed by parasitized erythrocytes as compared to uninfected erythrocytes. Further study revealed that carbohybrid 12 arrests the growth of parasite at trophozoite and schizonts stage during course of progression through asexual blood stages. Mechanistically, it was shown that the carbohybrid 12 binds to α,β-heterodimer of tubulin and affects microtubule dynamics. Conclusion: These findings show carbohydrate group fusion to 4-hydroxycoumarin precursor resulted in pyrano-pyranones derivatives with better solubility, enhanced uptake and improved selectivity. This data confirms that, carbohydrate fused pyrano[3,2-c]pyranones carbohybrids are effective candidates for anti-malarial interventions against P. falciparum. © 2019 The Author(s).
Erratum: Enhanced uptake, high selective and microtubule disrupting activity of carbohydrate fused pyrano-pyranones derived from natural coumarins attributes to its anti-malarial potential (Malaria Journal (2019) 18 (346) DOI: 10.1186/s12936-019-2971-z)
(BioMed Central Ltd., 2020) Sonal Gupta; Juveria Khan; Priti Kumari; Chintam Narayana; R. Ayana; Malabika Chakrabarti; Ram Sagar; Shailja Singh
Please note, following publication of the original article [1], the authors have advised of three errors that are present in the published article. Firstly, the two instances of 'Albumax II' in the 'Methods' section of the article are incorrect: the reagent 'Albumax I' should be referred to instead. Secondly, 'giemsa' (also referred to in the 'Methods' section) should be capitalized, as 'Giemsa'. Finally, an incorrect version of Fig. 4 has been incorporated in the article; please find the correct version of Fig. 4 in this article, for reference. © 2020 The Author(s).
Glycohybrid molecules in medicinal chemistry: Present status and future prospective
(Elsevier, 2020) Priti Kumari; Chintam Narayana; Ghanshyam Tiwari; Ram Sagar
Hybrid molecules combine two distinct biologically relevant molecules that act at different biological targets with new mechanism are becoming molecules for interest among medicinal chemist and biological chemists. Hybrid molecules are usually defined as a molecular framework in which a linker, often a stable hydrocarbon chain, heterocyclic ring connects the two biologically relevant molecules with altered bioactivity profile. Carbohydrates play important roles in the natural world as diverse as energy storage, molecular recognition for intracellular trafficking or interactions between pathogenic bacteria and viruses and the surfaces of vertebrate’s cells. The carbohydrates present inside and at the surface of cells mediate many biological processes that are fundamentally important for human health. In the current chapter we have covered the medicinal chemistry aspects of recently reported glycohybrid molecules with respect to their anticancer, antiviral, antibacterial, antifungal, immununomodulatory, PTP1B inhibitors, carbonic anhydrase inhibitors, antimalarial, glycosidase inhibitors, galectin-3-inhibitors and anti-inflammatory activity. © 2020 Elsevier Inc. All rights reserved.
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).
Regioselective Synthesis of Chirally Enriched Tetrahydrocarbazolones and Tetrahydrocarbazoles
(American Chemical Society, 2018) Chintam Narayana; Priti Kumari; Ram Sagar
A new one-step, reagent-directed regioselective synthesis of chirally enriched tetrahydrocarbazolones and tetrahydrocarbazoles from a common type of substrate has been developed. The salient features of this method include inherited stereodiversity, a broad substrate scope, a quick reaction time, and a benign catalyst. The method is applicable to the synthesis of a bioactive cryptosanguinolentine precursor. Copyright © 2018 American Chemical Society.
Stereoselective synthesis of carbohydrate fused pyrano[3,2-c]pyranones as anticancer agents
(Royal Society of Chemistry, 2018) Priti Kumari; Sonal Gupta; Chintam Narayana; Shakeel Ahmad; Nidhi Vishnoi; Shailja Singh; Ram Sagar
Pyrano[3,2-c]pyranone is an important structural motif present in many natural products exhibiting diverse biological activities. Two series of carbohydrate fused pyrano[3,2-c]pyranone derivatives (n = 20) were efficiently synthesized starting from 2-C-formyl galactal and 2-C-formyl glucal, reacting with various 4-hydroxycoumarins in a very short reaction time (10 min) under microwave assisted conditions. The anticancer activity of these synthesized pyrano[3,2-c]pyranones was determined in detail through cellular assays against MCF-7 (breast), MDA-MB-231 (breast) and HepG2 (liver) cancer cell lines. The newly synthesized pyrano[3,2-c]pyranones were screened for their cell-viability and anti-proliferative activity against MCF-7, MDA-MB-231 and HepG2 cell lines. Compounds 12, 13 and 14 exhibited high growth inhibitory potencies selectively against MCF-7 cells with half-maximal inhibitory concentration (IC50) values of 19.9, 14.5 and 10.9 μM respectively. Compounds 12, 13, 14, 15 and 19 inhibited the growth of MDA-MB-231 cells (breast) by 43, 44, 37, 31 and 45% respectively. However, no inhibitory effect was observed for these compounds in the human liver cancer cell line (HepG2) and normal cell lines (HEK293, human embryonic kidney cells). Mechanistic studies showed that these compounds alter the cell morphology and cause G2/M arrest in MCF-7. Further studies showed that compounds 12, 13 and 14 significantly inhibited cell migration which was accompanied by altered microtubule distribution. An enhanced accumulation of these compounds in cells was observed as compared to the 4-hydroxycoumarins precursor in the intracellular uptake assay. These findings confirm that carbohydrate fused pyrano[3,2-c]pyranones are better candidates for anticancer activity. © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.
Stereoselective synthesis of natural product inspired carbohydrate fused pyrano[3,2-: C] quinolones as antiproliferative agents
(Royal Society of Chemistry, 2018) Priti Kumari; Chintam Narayana; Shraddha Dubey; Ashish Gupta; Ram Sagar
Pyrano[3,2-c]quinolone structural motifs are commonly found in natural products with diverse biological activities. As part of a research programme aimed at developing the efficient synthesis of natural product-like small molecules, we designed and developed the microwave assisted, facile stereoselective synthesis of two series of carbohydrate fused pyrano[3,2-c]quinolone derivatives (n = 23) starting from 2-C-formyl galactal and 2-C-formyl glucal, reacting with various 4-hydroxyquinolones in shorter reaction times (15-20 min). The antiproliferative activity of these synthesized pyrano[3,2-c]quinolones was determined against MCF-7 (breast) and HepG2 (liver) cancer cells. The selected library members displayed low micromolar (3.53-9.68 μM) and selective antiproliferative activity. These findings on carbohydrate fused pyrano[3,2-c]quinolone derivatives are expected to provide new leads for anticancer drug discovery. © 2018 The Royal Society of Chemistry.
Synthesis of new triazole linked carbohybrids with ROS-mediated toxicity in breast cancer
(Royal Society of Chemistry, 2019) Priti Kumari; Shraddha Dubey; Sneha Venkatachalapathy; Chintam Narayana; Ashish Gupta; Ram Sagar
Carbohybrids are an important class of molecules which exhibit diverse biological activities and are present as structural motifs in many natural products. Two series of new triazole linked N-glycosides of coumarins and quinolones (n = 27) were efficiently synthesized starting from 1-azido-2,3,4,6-tetra-O-acetyl β-d-glucose and 1-azido-2,3,4,6-tetra-O-acetyl β-d-galactose reacting with various 4-O-propargyl coumarins and 4-O-propargyl quinolones in shorter reaction time (30 min) under microwave assisted conditions. Anticancer activity of these newly synthesized triazole linked N-glycosides of coumarins and quinolones was determined in detail through cellular assays against MCF-7 (breast cancer cell line), HepG2 (liver cancer cell line), HCT-116 (colon cancer cell line) and Huh-7.5 cell lines. The selected library member displayed low micromolar (IC50 10.97 μM) and selective toxicity against the breast cancer cell line (MCF-7). Mechanistic studies showed that the anticancer activity of the active compound was because of the generation of reactive oxygen species (ROS). This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.
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
Triazole Linked N-Acetylglucosamine Based Gelators for Crude Oil Separation and Dye Removal
(American Chemical Society, 2019) Chintam Narayana; Priti Kumari; Ghanshyam Tiwari; Ram Sagar
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. Copyright © 2019 American Chemical Society.