Synthesis of 1,4-anhydro-D-xylitol heteroanalogues of the naturally occurring glycosidase inhibitor salacinol and their evaluation as glycosidase inhibitors

2002 ◽  
Vol 80 (8) ◽  
pp. 937-942 ◽  
Author(s):  
Ahmad Ghavami ◽  
Blair D Johnston ◽  
Matthew D Maddess ◽  
Sarah M Chinapoo ◽  
Morten T Jensen ◽  
...  
Keyword(s):  
Significant Inhibition ◽  
Nucleophilic Attack ◽  
Ammonium Ion ◽  
Aqueous Extracts ◽  
Glycosidase Inhibitors ◽  
Synthetic Strategy ◽  
Naturally Occurring ◽  
Glycosidase Inhibitor ◽  
Salacia Reticulata

The syntheses of two 1,4-anhydro-D-xylitol heteroanalogues (8 and 9) of the naturally occurring sulfonium ion, salacinol (3), containing a sulfur or nitrogen atom in the ring are described. Salacinol (3) is one of the active principles in the aqueous extracts of Salacia reticulata that are traditionally used in Sri Lanka and India for the treatment of Type 2 diabetes. The synthetic strategy relies on the nucleophilic attack of sulfur or nitrogen analogues of 1,4-anhydro-D-xylitol at the least-hindered carbon of 2,4-O-benzylidene-L-erythritol-1,3-cyclic sulfate. The sulfonium ion 8 inhibited barley-α-amylase (AMY1) and porcine pancreatic-α-amylase (PPA), with Ki values of 109 ± 11 and 55 ± 5 µM, respectively. In contrast, the ammonium ion 9 showed no significant inhibition of either AMY1 or PPA. Compounds 8 and 9 also showed no significant inhibition of glucoamylase.Key Words: glycosidase inhibitors, salacinol analogues, anhydro-D-xylitol heteroanalogues, enzyme inhibition.

Synthesis of Selenium Analogues of the Naturally Occurring Glycosidase Inhibitor Salacinol and Their Evaluation as Glycosidase Inhibitors†

2002 ◽  
Vol 124 (28) ◽  
pp. 8245-8250 ◽  
Author(s):  
Blair D. Johnston ◽  
Ahmad Ghavami ◽  
Morten T. Jensen ◽  
Birte Svensson ◽  
B. Mario Pinto
Keyword(s):  
Glycosidase Inhibitors ◽  
Naturally Occurring ◽  
Glycosidase Inhibitor

Design and synthesis of selenonium and sulfonium ions related to the naturally occurring glucosidase inhibitor salacinol

2006 ◽  
Vol 84 (10) ◽  
pp. 1351-1362 ◽  
Author(s):  
Hui Liu ◽  
B Mario Pinto
Keyword(s):  
Nucleophilic Attack ◽  
Significant Activity ◽  
The Novel ◽  
Glycosidase Inhibitors ◽  
Design And Synthesis ◽  
Glucosidase Inhibitor ◽  
Naturally Occurring ◽  
Sulfonium Ions ◽  
Stereogenic Centers ◽  
Cyclic Sulfates

Four series of analogues of the naturally occurring glucosidase inhibitor salacinol were synthesized for structure–activity studies with different glycosidase enzymes. The target zwitterionic compounds were synthesized by means of nucleophilic attack at the least-hindered carbon atom of the 1,3-cyclic sulfates derived from D-glucose and D-mannose by the isopropylidene-protected 1,4-anhydro-4-thio- and seleno-D-allitols and the 4-thio- and seleno-L-allitols. Deprotection of the coupled products afforded the novel sulfonium and selenonium ions containing polyhy droxylated acyclic chains of four and six carbons, with different stereochemistry at the stereogenic centers and with 1,4-anhydro-4-seleno or 4-thio-D- or L- alditol heterocyclic rings. The compounds showed no significant activity against recombinant human maltase glucoamylase (MGA), a critical intestinal glucosidase involved in the processing of oligosaccharides of glucose into glucose itself.Key words: glycosidase inhibitors, zwitterionic, selenonium salts, sulfonium salts, cyclic sulfates, L-ascorbic acid, D-gulonic-γ-lactone.

Synthesis of zwitterionic selenonium and sulfonium sulfates from D-mannose as potential glycosidase inhibitors

2006 ◽  
Vol 84 (4) ◽  
pp. 497-505 ◽  
Author(s):  
Hui Liu ◽  
B Mario Pinto
Keyword(s):  
Membered Ring ◽  
The Novel ◽  
Glycosidase Inhibitors ◽  
Naturally Occurring ◽  
Structure Activity ◽  
Glycosidase Inhibitor ◽  
Ring Core

Four chain-extended analogues of the naturally occurring glycosidase inhibitor salacinol were synthesized for structure–activity studies with different glycosidase enzymes. The syntheses involved the reaction of isopropylidene-protected 1,4-thio- and 1,4-seleno-D-talitols and 1,5-thio- and 1,5-seleno-L-gulitols, derived from D-mannose, with a benzylidene- and isopropylidene-protected 1,3-cyclic sulfate, also derived from D-mannose. Deprotection of the products afforded the novel selenonium and sulfonium sulfates composed of heterocyclic five- and six-membered ring core structures with pendant polyhydroxylated, acyclic chains of six carbon atoms.Key words: glycosidase inhibitors, zwitterionic selenonium and sulfonium sulfates, cyclic sulfate

Sulfonium-ion glycosidase inhibitors isolated from Salacia species used in traditional medicine, and related compounds

2009 ◽  
Vol 74 (7-8) ◽  
pp. 1117-1136 ◽  
Author(s):  
Sankar Mohan ◽  
B. Mario Pinto
Keyword(s):  
Type 2 Diabetes ◽  
Therapeutic Potential ◽  
Ayurvedic Medicine ◽  
Glycosidase Inhibitors ◽  
Bioactive Components ◽  
Stereochemical Structure ◽  
Naturally Occurring ◽  
The Family ◽  
Related Compounds

A novel class of naturally-occurring glycosidase inhibitors, having sulfonium sulfate structures, has been isolated as bioactive components from Indian plants, belonging to the Salacia genus in the family Celastraceae, and used in Ayurvedic medicine for the treatment of type-2 diabetes. Thus far, five such sulfonium salts, namely, salacinol, kotalanol, salaprinol, ponkoranol and de-O-sulfonated kotalanol, have been isolated from this plant species. These structurally unique zwitterionic glycosidase inhibitors have received much attention due to their therapeutic potential in the treatment of type-2 diabetes. We recently reported a review article which focused mainly on salacinol and related analogues. The present review presents an update on the remaining four compounds from this class of glycosidase inhibitors, with respect to their isolation, glucosidase inhibitory activities, and synthesis. In addition, progress towards the stereochemical structure elucidation of kotalanol, through synthesis of analogues, is described. Review with 42 references.

scholarly journals The Potential for SARS-CoV-2 to Evade Both Natural and Vaccine-induced Immunity

2020 ◽  
Author(s):  
Emily Shang ◽  
Paul Axelsen
Keyword(s):  
Human Infection ◽  
Antibody Binding ◽  
Spike Protein ◽  
Wild Type ◽  
Binding Interface ◽  
Naturally Occurring ◽  
Binding Interfaces ◽  
Induced Immunity ◽  
Wild Type Form

SARS-CoV-2 attaches to the surface of susceptible cells through extensive interactions between the receptor binding domain (RBD) of its spike protein and angiotensin converting enzyme type 2 (ACE2) anchored in cell membranes. To investigate whether naturally occurring mutations in the spike protein are able to prevent antibody binding, yet while maintaining the ability to bind ACE2 and viral infectivity, mutations in the spike protein identified in cases of human infection were mapped to the crystallographically-determined interfaces between the spike protein and ACE2 (PDB entry 6M0J), antibody CC12.1 (PDB entry 6XC2), and antibody P2B-2F6 (PDB entry 7BWJ). Both antibody binding interfaces partially overlap with the ACE2 binding interface. Among 16 mutations that map to the RBD:CC12.1 interface, 11 are likely to disrupt CC12.1 binding but not ACE2 binding. Among 12 mutations that map to the RBD:P2B-2F6 interface, 8 are likely to disrupt P2B-2F6 binding but not ACE2 binding. As expected, none of the mutations observed to date appear likely to disrupt the RBD:ACE2 interface. We conclude that SARS-CoV-2 with mutated forms of the spike protein may retain the ability to bind ACE2 while evading recognition by antibodies that arise in response to the original wild-type form of the spike protein. It seems likely that immune evasion will be possible regardless of whether the spike protein was encountered in the form of infectious virus, or as the immunogen in a vaccine. Therefore, it also seems likely that reinfection with a variant strain of SARS-CoV-2 may occur among people who recover from Covid-19, and that vaccines with the ability to generate antibodies against multiple variant forms of the spike protein will be necessary to protect against variant forms of SARS-CoV-2 that are already circulating in the human population.

scholarly journals In Vitro Antioxidant and Anti-Diabetic Potential of Gymnema Sylvestre Methanol Leaf Extract

2017 ◽  
Vol 13 (36) ◽  
pp. 218 ◽  
Author(s):  
Ibrahim A. ◽  
Babandi A. ◽  
Tijjani A.A. ◽  
Murtala Y. ◽  
Yakasai H.M. ◽  
...  
Keyword(s):  
Normal Control ◽  
Leaf Extract ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Significant Inhibition ◽  
Alpha Amylase ◽  
Gymnema Sylvestre ◽  
Total Flavonoids Content

Some medicinal plants and their purified derivatives have demonstrated beneficial therapeutic potentials for many centuries. They have been reported to exhibit antioxidant activity, reducing the oxidative stress in cells and are therefore useful in the treatment of many human diseases, including diabetes and other non-communicable diseases. This study evaluated antioxidative activity and enzymatic (alpha-amylase and alphaglucosidase) inhibitory potentials of Gymnema sylvestre methanolic leaf extract (GSMLE) using standard methods. Phytochemical screening revealed the presence of alkaloids, tannins, saponins, steroids, terpenoids and flavonoids. The total phenolics and total flavonoids content in the extract were found to be 6.629±0.745 (µg/ml of catechol equivalent) and 0.004±0.0012 (µg/ml of quercetin equivalent) respectively. GSMLE was shown to have radical scavenging activity against DPPH (290.54 ± 39.72 %), hydroxyl radical (86.507 ± 23.55 %) and hydrogen peroxide (45.25 ± 25.23 %). The level of SOD was significantly decreased in H2O2 induced and H2O2+extract induced when compared with normal control (p<0.05); the level of GSH was significantly increased in H2O2 induced control and significantly decreased in H2O2+extract induced test when compared to normal control. GSH was also decreased significantly in H2O2+extract induced when compared to H2O2 induced control (p<0.05). The extract also demonstrated significant inhibition of alpha-glucosidase (IC50 182.26 ±1.05μg/ml) when compared with standard acarbose (IC50 189.52±0.46) and was more potent than the arcarbose on alpha-amylase inhibition with IC50 of 195.3±4.40 and 200.05±7.16 respectively. These findings may therefore, stress the potentiality of using Gymnema sylvestre as a natural remedy for the management of type 2 diabetes.

Fluorescent oxazoles from quinones for bioimaging applications

RSC Advances ◽  
2016 ◽  
Vol 6 (79) ◽  
pp. 76056-76063 ◽  
Author(s):  
Gleiston G. Dias ◽  
Pamella V. B. Pinho ◽  
Hélio A. Duarte ◽  
Jarbas M. Resende ◽  
Andressa B. B. Rosa ◽  
...  
Keyword(s):  
Excited State ◽  
Proton Transfer ◽  
Intramolecular Proton Transfer ◽  
Synthetic Strategy ◽  
Naturally Occurring ◽  
Oxazole Derivatives

This work describes a synthetic strategy for the syntheses of four new fluorescent excited state intramolecular proton transfer (ESIPT) prone oxazole derivatives synthesized from lapachol, a naturally occurring naphthoquinone isolated from the Tabebuia species (ipe tree).

scholarly journals Genetic marker studies of poliovirus: II. Strains isolated from cases of poliomyelitis associated with the administration of live attenuated vaccine

1967 ◽  
Vol 65 (1) ◽  
pp. 77-84 ◽  
Author(s):  
Yvonne E. Cossart
Keyword(s):  
Oral Vaccine ◽  
Paralytic Poliomyelitis ◽  
Live Attenuated Vaccine ◽  
Naturally Occurring ◽  
South Wales ◽  
Vaccine Type ◽  
Marker Studies ◽  
Type 3

Strains of poliovirus were obtained from 13 of the 18 persons in England and Wales with paralytic episodes after administration of oral vaccine in 1962. They have been studied using three marker tests: the R.C.T.40 test, intratypic serodifferentiation and inhibition by dextran sulphate. For comparison a number of strains from subjects with non-paralytic vaccine-associated reactions and from patients with paralytic poliomyelitis not related to vaccine were also tested.Of the eight patients excreting type 1 strains seven came from South Wales where an outbreak was in progress. They all resemble naturally occurring strains from the outbreak in growing at 39·3° but not at 39·8° C.Only one subject excreted type 2 virus which was of vaccine type.The type 3 strains included a series from a family group where a range of results from vaccine to the wild range was obtained. Three other patients with vaccineassociated paralysis excreted type 3 strains with the characteristic of naturally occurring strains.

scholarly journals Postprandial Glycemic and Insulinemic Effects of the Addition of Aqueous Extracts of Dried Corn Silk, Cumin Seed Powder or Tamarind Pulp, in Two Forms, Consumed with High Glycemic Index Rice

Foods ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 437
Author(s):  
Haldar ◽  
Gan ◽  
Tay ◽  
Ponnalagu ◽  
Henry
Keyword(s):  
Glycemic Index ◽  
Plain Water ◽  
Aqueous Extracts ◽  
Traditional Foods ◽  
Postprandial Glycemia ◽  
Randomized Controlled Clinical Trials ◽  
Corn Silk ◽  
High Glycemic Index ◽  
Specific Health

Several plant-based traditional ingredients in Asia are anecdotally used for preventing and/or treating type 2 diabetes. We investigated three such widely consumed ingredients, namely corn silk (CS), cumin (CU), and tamarind (TA). The aim of the study was to determine the effects of aqueous extracts of these ingredients consumed either as a drink (D) with high-glycemic-index rice or added to the same amount of rice during cooking (R) on postprandial glycemia (PPG), insulinemia (PPI), and blood pressure (BP), over a 3 h measurement period. Eighteen healthy Chinese men (aged 37.5 ± 12.5 years, BMI 21.8 ± 1.67 kg/m2) took part in a randomized crossover trial, each completing up to nine sessions. Compared to the control meal (plain rice + plain water), the addition of test extracts in either form did not modulate PPG, PPI, or BP. However, the extracts when added within rice while cooking gave rise to significantly lower PPI than when consumed as a drink (p < 0.01). Therefore, the form of consumption of phytochemical-rich ingredients can differentially modulate glucose homeostasis. This study also highlights the need for undertaking randomized controlled clinical trials with traditional foods/components before claims are made on their specific health effects.

scholarly journals Cepharanthine: a review of the antiviral potential of a Japanese-approved alopecia drug in COVID-19

2020 ◽  
Vol 72 (6) ◽  
pp. 1509-1516 ◽  
Author(s):  
Moshe Rogosnitzky ◽  
Paul Okediji ◽  
Igor Koman
Keyword(s):  
Viral Entry ◽  
Cytokine Production ◽  
Therapeutic Potential ◽  
Antiviral Agent ◽  
Drug Repurposing ◽  
Preclinical Model ◽  
No Production ◽  
Drug Of Choice ◽  
Naturally Occurring

AbstractCepharanthine (CEP) is a naturally occurring alkaloid derived from Stephania cepharantha Hayata and demonstrated to have unique anti-inflammatory, antioxidative, immunomodulating, antiparasitic, and antiviral properties. Its therapeutic potential as an antiviral agent has never been more important than in combating COVID-19 caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) virus. Cepharanthine suppresses nuclear factor-kappa B (NF-κB) activation, lipid peroxidation, nitric oxide (NO) production, cytokine production, and expression of cyclooxygenase; all of which are crucial to viral replication and inflammatory response. Against SARS-CoV-2 and homologous viruses, CEP predominantly inhibits viral entry and replication at low doses; and was recently identified as the most potent coronavirus inhibitor among 2406 clinically approved drug repurposing candidates in a preclinical model. This review critically analyzes and consolidates available evidence establishing CEP’s potential therapeutic importance as a drug of choice in managing COVID-19 cases.

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