The altered gating of the mutant CFTR chloride channel cystic fibrosis (CF) may be corrected by s... more The altered gating of the mutant CFTR chloride channel cystic fibrosis (CF) may be corrected by small molecules called potentiators. We present a molecular scale simulation system for the discovery of ΔF508-CFTR soluble potentiators. Results report the design, ADME-Tox prediction, synthesis, solubility determination and in vitro biological evaluation of two 1,4-dihydropyridines (DHPs). Compound 1 shows a promising ADME-Tox profile and good potency.
4-Phenyl-3-furoxancarbonitrile (2) affords nitric oxide under the action of thiol cofactors. Two ... more 4-Phenyl-3-furoxancarbonitrile (2) affords nitric oxide under the action of thiol cofactors. Two principal products were isolated in the reaction with thiophenol: the phenylcyanoglyoxime (6) and 5-amino-3-phenyl-4-(phenylthio)isoxazole (7). Mechanisms which could account for the formation of these two products are discussed. Compound 2 is an efficient activator of the rat lung soluble guanylate cyclase, displays high vasodilatory activity on strips of rat thoracic aorta precontracted with noradrenaline, and is a potent inhibitor of platelet aggregation.
ABSTRACT The photochemical transformation of N,N-diethyl-m-toluamide (DEET), one of the most wide... more ABSTRACT The photochemical transformation of N,N-diethyl-m-toluamide (DEET), one of the most widespread and efficient mosquito repellents, has been investigated. Initially, photoinduced DEET degradation was investigated in liquid samples, at 20 degrees C and 0 degrees C, and in ice (-15 degrees C), aimed to simulate all possible photoinduced processes occurring in water and in cold environments. Under UV-illumination, DEET degradation was more efficient in ice than in water. The evaluation of transformation products (TPs) formed during the photolysis in solution and in ice evidences mostly the same degradation products, but with different concentration ratio and some peculiar differences. An hypothesis about what kind of processes may play a role is reported. In solution, the oxidative process mostly involved were (poly)hydroxylation or oxidation of the hydroxyl groups, while in ice N-dealkylation and monohydroxylation prevail. Finally, DEET and its TPs were searched out in snow and river water in wintertime.
The altered gating of the mutant CFTR chloride channel cystic fibrosis (CF) may be corrected by s... more The altered gating of the mutant CFTR chloride channel cystic fibrosis (CF) may be corrected by small molecules called potentiators. We present a molecular scale simulation system for the discovery of ΔF508-CFTR soluble potentiators. Results report the design, ADME-Tox prediction, synthesis, solubility determination and in vitro biological evaluation of two 1,4-dihydropyridines (DHPs). Compound 1 shows a promising ADME-Tox profile and good potency.
4-Phenyl-3-furoxancarbonitrile (2) affords nitric oxide under the action of thiol cofactors. Two ... more 4-Phenyl-3-furoxancarbonitrile (2) affords nitric oxide under the action of thiol cofactors. Two principal products were isolated in the reaction with thiophenol: the phenylcyanoglyoxime (6) and 5-amino-3-phenyl-4-(phenylthio)isoxazole (7). Mechanisms which could account for the formation of these two products are discussed. Compound 2 is an efficient activator of the rat lung soluble guanylate cyclase, displays high vasodilatory activity on strips of rat thoracic aorta precontracted with noradrenaline, and is a potent inhibitor of platelet aggregation.
ABSTRACT The photochemical transformation of N,N-diethyl-m-toluamide (DEET), one of the most wide... more ABSTRACT The photochemical transformation of N,N-diethyl-m-toluamide (DEET), one of the most widespread and efficient mosquito repellents, has been investigated. Initially, photoinduced DEET degradation was investigated in liquid samples, at 20 degrees C and 0 degrees C, and in ice (-15 degrees C), aimed to simulate all possible photoinduced processes occurring in water and in cold environments. Under UV-illumination, DEET degradation was more efficient in ice than in water. The evaluation of transformation products (TPs) formed during the photolysis in solution and in ice evidences mostly the same degradation products, but with different concentration ratio and some peculiar differences. An hypothesis about what kind of processes may play a role is reported. In solution, the oxidative process mostly involved were (poly)hydroxylation or oxidation of the hydroxyl groups, while in ice N-dealkylation and monohydroxylation prevail. Finally, DEET and its TPs were searched out in snow and river water in wintertime.
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Papers by Claudio Medana