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Your search keyword '"Antonella Messore"' showing total 2 results
Start Over Author "Antonella Messore" Journal journal of enzyme inhibition and medicinal chemistry
2 results on '"Antonella Messore"'

1. Inhibition of Leishmania infantum trypanothione reductase by diaryl sulfide derivatives

Author

Francesco Saccoliti, Gabriella Angiulli, Giovanni Pupo, Luca Pescatori, Valentina Noemi Madia, Antonella Messore, Gianni Colotti, Annarita Fiorillo, Luigi Scipione, Marina Gramiccia, Trentina Di Muccio, Roberto Di Santo, Roberta Costi, and Andrea Ilari

Subjects
Diaryl sulfide derivatives, Leishmania infantum, trypanothione reductase, trypanothione reductase inhibition, X-ray crystal structure, Therapeutics. Pharmacology, RM1-950
Abstract

The study presented here aimed at identifying a new class of compounds acting against Leishmania parasites, the causative agent of Leishmaniasis. For this purpose, the thioether derivatives of our in-house library have been evaluated in whole-cell screening assays in order to determine their in vitro activity against Leishmania protozoan. Among them, promising results have been achieved with compound RDS 777 (6-(sec-butoxy)-2-((3-chlorophenyl)thio)pyrimidin-4-amine) (IC50 = 29.43 µM), which is able to impair the mechanism of the parasite defence against the reactive oxygen species by inhibiting the trypanothione reductase (TR) with high efficiency (Ki 0.25 ± 0.18 µM). The X-ray structure of L. infantum TR in complex with RDS 777 disclosed the mechanism of action of this compound that binds to the catalytic site and engages in hydrogen bonds the residues more involved in the catalysis, namely Glu466', Cys57 and Cys52, thereby inhibiting the trypanothione binding and avoiding its reduction.

Published
2017
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2. Hypoglycemic activity of curcumin synthetic analogues in alloxan-induced diabetic rats

Author

Jameel G. Jargar, Luca Pescatori, Salim A Dhundasi, Kusal K Das, Antonella Messore, Swati N Tikare, Nima Razzaghi-Asl, Giuliana Cuzzucoli Crucitti, Roberto Di Santo, Luciano Saso, and Roberta Costi

Subjects
0301 basic medicine, Drug, Blood Glucose, Male, medicine.medical_specialty, Curcumin, media_common.quotation_subject, Administration, Oral, Type 2 diabetes, Pharmacology, curcumin, diabetic rats, hypoglycemic, in vitro, OGTT, synthesis, Diabetes Mellitus, Experimental, 03 medical and health sciences, chemistry.chemical_compound, Structure-Activity Relationship, In vivo, Alloxan, Internal medicine, Drug Discovery, Medicine, Structure–activity relationship, Animals, Hypoglycemic Agents, Rats, Wistar, media_common, Dose-Response Relationship, Drug, Molecular Structure, business.industry, General Medicine, Glucose Tolerance Test, medicine.disease, In vitro, Rats, 030104 developmental biology, Endocrinology, Glucose, chemistry, business, Glipizide, medicine.drug
Abstract

The currently available therapies for type 2 diabetes have been unable to achieve normoglycemic status in the majority of patients. The reason may be attributed to the limitations of the drug itself or its side effects. In an effort to develop potent and safe oral antidiabetic agents, we evaluated the in vitro and in vivo hypoglycemic effects of 10 synthetic polyphenolic curcumin analogues on alloxan-induced male diabetic albino rats. In vitro studies showed 7-bis(3,4-dimethoxyphenyl)hepta-1,6-diene-3,5-dione (4) to be the most potential hypoglycemic agent followed by 1,5-bis(4-hydroxy-3-methoxyphenyl)penta-1,4-dien-3-one (10). Structure activity relationship (SAR) of the tested compounds was elucidated and the results were interpreted in terms of in vitro hypoglycemic activities. Furthermore, oral glucose tolerance test (OGTT) with compounds 4, 10 and reference hypoglycemic drug glipizide showed that compound 4 and glipizide had relatively similar effects on the reduction of blood glucose levels within 2 h. Thus, compound 4 might be regarded as a potential hypoglycemic agent being able to reduce glucose concentration both in vitro and in vivo.

Published
2015

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