ABSTRACT
The optical and electron properties of three different s-triazine derivatives are investigated to ascertain the role of the donor acceptor character in amine-triazine systems depending on the bridging radical of the ammine group. The three derivatives were obtained starting from three different ammine compounds allowing to achieve a structure with a triazine core, surrounded by three ammine group and terminated with cyano or methyl or oxy-methyl functional group. Experimental optical data were interpreted in view of the electronic insights gathered by means of density functional theory simulations on base compounds. As compared to the reference electron donating triazine core, the resulting compounds show different donor acceptor character, from electron accepting to electron donating feature. Among the analyzed derivatives, the cyano terminated ammino-triazine compound shows the most promising optical features for photonics and lighting applications.
ABSTRACT
New linear and cyclic guanidines were synthesized and tested in vitro for their antifungal activity toward clinically relevant strains of Candida species, in comparison to fluconazole. Macrocyclic compounds showed a minimum inhibitory concentration in the micromolar range and a biological activity profile in some cases better than that of fluconazole. One macrocyclic derivative was also tested against Aspergillus species and showed high antifungal activity comparable to that of amphotericin B and itraconazole.
Subject(s)
Aspergillus/drug effects , Candida/drug effects , Guanidine/analogs & derivatives , Macrocyclic Compounds/chemical synthesis , Macrocyclic Compounds/pharmacology , Urea/analogs & derivatives , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Drug Design , Guanidine/chemical synthesis , Guanidine/chemistry , Guanidine/pharmacology , Humans , Macrocyclic Compounds/chemistry , Microbial Sensitivity Tests , Urea/chemical synthesis , Urea/chemistry , Urea/pharmacologyABSTRACT
A novel compound inhibiting HIV-1 integrase has been identified by means of virtual screening techniques. A small family of structurally related molecules has been synthesized and biologically evaluated with some of the compounds possessing micromolar activity both in enzymatic and cellular assays.
Subject(s)
Anti-HIV Agents/chemistry , HIV Integrase Inhibitors/chemistry , HIV Integrase/chemistry , HIV-1/drug effects , Rhodanine/chemistry , Thiobarbiturates/chemistry , Thiohydantoins/chemistry , Anti-HIV Agents/chemical synthesis , Anti-HIV Agents/pharmacology , Cell Line , HIV Integrase/metabolism , HIV Integrase Inhibitors/chemical synthesis , HIV Integrase Inhibitors/pharmacology , Humans , Rhodanine/chemical synthesis , Structure-Activity Relationship , Thiobarbiturates/chemical synthesis , Thiohydantoins/chemical synthesisABSTRACT
We report the synthesis and evaluation of aminoalkylguanidine analogues and derivatives in C57BL/KsJ db/db diabetic mice, following identification by random screening of 1a and 1b as potential antihyperglycemics and/or modulators of food intake. These compounds are related to galegine, a gamma,gamma-dimethylallylguanidine. Between the newly identified compounds, 1h N-(cyclopropylmethyl)- N'-(4-(aminomethyl)cyclohexylmethyl)guanidine showed the most balanced activity as antihyperglycemic and food intake-reducing agent.
Subject(s)
Anti-Obesity Agents/chemical synthesis , Eating/drug effects , Guanidines/chemical synthesis , Hypoglycemic Agents/chemical synthesis , Animals , Anti-Obesity Agents/chemistry , Anti-Obesity Agents/pharmacology , Drinking/drug effects , Guanidines/chemistry , Guanidines/pharmacology , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Mice , Mice, Inbred C57BL , Structure-Activity RelationshipABSTRACT
The identification of a novel hit compound as integrase binding inhibitor has been accomplished by means of virtual screening techniques. A small family of structurally related molecules has been synthesized and biologically evaluated with one of the compounds showing an IC(50)=12 microM.
Subject(s)
HIV Integrase Inhibitors/chemical synthesis , HIV Integrase Inhibitors/pharmacology , HIV-1/drug effects , Computer Simulation , Databases, Factual , Drug Evaluation, Preclinical , HIV-1/enzymology , Indicators and Reagents , Ligands , Models, MolecularABSTRACT
Lewis acid mediated endo-cyclisation of trimethylsilylmethylenecyclopropyl imines provides a stereoselective route to indolizidines via a novel cascade sequence.
