Stereoselective synthesis of carbohydrate fused pyrano[3,2-<i>c</i>]pyranones as anticancer agents

Kumari, Priti; Gupta, Sonal; Narayana, Chintam; Ahmad, S.; Vishnoi, Nidhi; Singh, Shailja; Sagar, Ram

doi:10.1039/c8nj01395k

Cited by 23 publications

(19 citation statements)

References 29 publications

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“…The results showed that most of carbohydrate fused compounds inhibited growth of parasite in vitro (Additional file 1: Table S1). These compounds exhibited no cytotoxicity even at higher concentration of 100 µM against HepG2 cells (liver hepatocellular carcinoma) as described in the previous work [8].…”

Section: Resultssupporting

confidence: 55%

“…This indicates that this compound is efficient against both the chloroquine sensitive and the resistant strains. Upon structural analysis of this compound as depicted by structure activity relationship (SAR) studies, carbohybrid 12 has 2-OMe group at C-2 position which might be playing an important role for its anti-malarial activity [8]. To assess whether the inhibitory potential of carbohybrid 12 is not due to haemolytic effect of compound itself, uninfected erythrocytes were incubated with different concentrations of compound (1–50 μM).…”

Section: Resultsmentioning

confidence: 99%

“…The structure of carbohydrate-fused pyrano[3,2-c]pyranone, carbohybrid 12 was established by 1D and 2D NMR (NOE, COSY and HSQC) experiments and comparing it with earlier spectral data. The details of the synthetic design and reaction optimization for the synthesis of these compounds can be obtained from the previous study [8].…”

Section: Methodsmentioning

confidence: 99%

“…Different derivatives of coumarin have been shown to inhibit cell proliferation via targeting microtubule dynamics in eukaryotes [9]. Carbohybrid 12 has shown inhibitory effects on mammalian tubulin as reported in the previous study [8]. This led to the hypothesis that P. falciparum growth inhibition induced by carbohybrid 12 is accredited to its anti-microtubule activity in the parasite.…”

Section: Introductionmentioning

confidence: 92%

“…The aim behind this hybridization was to improve their bioavailability and selectivity. Selected members from this library were found to possess anticancer activity [8]. Anti-malarial potential of these compounds was evaluated against P. falciparum 3D7 strain by growth inhibition assay.…”

Section: Introductionmentioning

confidence: 99%

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Enhanced uptake, high selective and microtubule disrupting activity of carbohydrate fused pyrano-pyranones derived from natural coumarins attributes to its anti-malarial potential

Gupta

Khan

Kumari

et al. 2019

Malar J

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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.

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Section: Resultssupporting

confidence: 55%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Enhanced uptake, high selective and microtubule disrupting activity of carbohydrate fused pyrano-pyranones derived from natural coumarins attributes to its anti-malarial potential

Gupta

Khan

Kumari

et al. 2019

Malar J

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Total Syntheses of Kirkamide and N‐acetyl ent‐Conduramine B‐1

et al. 2020

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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.

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Therapeutic applications of carbohydrate-based compounds: a sweet solution for medical advancement

Lalhmangaihzuala,

Vanlaldinpuia,

Khiangte

et al. 2024

Mol Divers

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Stereoselective synthesis of carbohydrate fused pyrano[3,2-c]pyranones as anticancer agents

Abstract: Efficient synthesis of pyrano[3,2-c]pyranones motif as fused carbohybrids and their anticancer activities reported.

Cited by 23 publications

References 29 publications

Enhanced uptake, high selective and microtubule disrupting activity of carbohydrate fused pyrano-pyranones derived from natural coumarins attributes to its anti-malarial potential

Enhanced uptake, high selective and microtubule disrupting activity of carbohydrate fused pyrano-pyranones derived from natural coumarins attributes to its anti-malarial potential

Total Syntheses of Kirkamide and N‐acetyl ent‐Conduramine B‐1

Therapeutic applications of carbohydrate-based compounds: a sweet solution for medical advancement

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