Search

Abstract: Neglected tropical diseases (NTDs) affect mainly poor and marginalized populations of tropical and subtropical areas in 150 countries. Many of the chemical processes involved in the synthesis of active pharmaceutical ingredients (APIs) are highly polluting and inefficient, both in terms of materials and energy-consuming. In this review, we present the green protocols developed in the last 10 years to access new small molecules with potential applications in the treatment of leishmania, tuberculosis, malaria, and Chagas disease. The use of alternative and efficient energy sources, like microwaves and ultrasound, as well as reactions using green solvents and solvent-free protocols, are discussed in this review.

The present study investigated a possible antidepressant-like effect of ((4-tert-butylcyclohexylidene)methyl) (4-methoxystyryl) sulfide (BMMS) by using the forced swimming test (FST) and the tail suspension test (TST) in Swiss mice. The contribution of serotoninergic, glutamatergic and nitrergic systems in the antidepressant-like activity of BMMS was evaluated. We also examined the involvement of monoamine oxidase (MAO)-A, MAO-B and Na+, K+-ATPase activities in prefrontal cortex of mice. BMMS, (0.1–10 mg/kg, intragastrically (i.g.)) and fluoxetine (32 mg/kg, i.g.) decreased the immobility time in the FST and TST. The anti-immobility effect of BMMS (10 mg/kg, i.g.) in the TST was prevented by the pretreatment of mice with WAY100635 (0.1 mg/kg, subcutaneously (s.c.), a 5-HT1A receptor antagonist), ketanserin (5 mg/kg, intraperitoneal (i.p.), a 5-HT2A/2C receptor antagonist), and partially blocked by ondansetron (1 mg/kg, i.p., a 5-HT3 receptor antagonist). The anti-immobility effect of BMMS (10 mg / kg, i.g.) was not avoided by pretreatment with MK-801 (0.01 mg/kg, s.c. a non-competitive N-methyl D-Aspartate (NMDA) receptor) in the TST. Pretreatment with L-arginine (500 mg/kg, i.p., a nitric oxide precursor) reversed partially the reduction in the immobility time elicited by BMMS (10 mg/kg, i.g.) in TST. BMMS altered Na+,K+-ATPase and MAO-A activities in prefrontal cortex of mice, but was not able to change the MAO-B activity. In conclusion, BMMS exerted an antidepressant-like effect in mice and serotonergic and nitrergic systems are involved in the antidepressant-like action of compound. BMMS modulated MAO-A and Na+, K+- ATPase activities in prefrontal cortex of mice.

Facile and efficient syntheses of 4‐(1H ‐pyrrol‐1‐yl)‐coumarins and 6‐(1H ‐pyrrol‐1‐yl)‐coumarins from the corresponding aminocoumarins are reported. The transformations were optimized and their corresponding scope and limitations were assessed. Selected (1H ‐pyrrol‐1‐yl)‐coumarins were further subjected to a mild thiocyanation, undergoing selective functionalization on the pyrrole nucleus. A set of 10 differently substituted compounds was submitted to activity testing against various fungal strains. It was found that the introduction of a SCN moiety increased the antifungal activity, turning some compounds into fungicidal agents, to the point that one of the thiocyanato derivatives displayed an antifungal profile comparable to those of fluconazole and nystatin. Fil: Brites, Nathan P.. Universidade Federal de Santa Maria; Brasil Fil: Dilelio, Marina C.. Universidade Federal de Santa Maria; Brasil Fil: Martins, Guilherme M.. Universidade Federal de Santa Maria; Brasil Fil: Carmo, Gabriele do. Universidade Federal de Santa Maria; Brasil Fil: Morel, Ademir F.. Universidade Federal de Santa Maria; Brasil Fil: Kaufman, Teodoro Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Silveira, Claudio C.. Universidade Federal de Santa Maria; Brasil

The Wittig-Horner mediated syntheses of phenothiazines carrying vinylsulfide and vinylselenide motifs attached to the aromatic ring(s) or connected to the central nitrogen atom of the heterocycle, and the subsequent study of their photophysical and electrochemical properties, are reported. These compounds were obtained as mixtures of geometric isomers, in good to excellent yields. To complete the study, a small set of vinylsulfoxide and vinylsulfone derivatives was also prepared from the corresponding oxidized phosphinoxides. The photophysical properties of the compounds were examined in solvents of varying polarity, in which they presented absorption maxima in the UV region, with molar absorptivity coefficients compatible with symmetry-allowed π–π* electronic transitions. The heterocyclic derivatives were fluorescent. Compounds bearing vinylsulfide moieties associated to the nitrogen atom of the heterocycle displayed less intense fluorescence than the phenothiazine derivatives carrying vinylchalcogenides bonded to the aromatic ring; the latter also exhibited more red-shifted absorption spectra, and Stokes shifts in the range 6115–8170 cm−1 with weak dependence of solvent polarity. The sulfoxide and sulfones displayed more red-shifted spectra than the corresponding sulfides. The cyclic voltammograms of all derivatives exhibited a common pattern of reversible or quasi-reversible processes in the anodic region, related to the phenothiazine unit.

A facile and efficient protocol for the highly selective direct sulfanylation of 3-bromocoumarins under DABCO promotion, was developed. The transformation took place with aromatic and aliphatic thiols as well as with α,ω-dithiols, affording the expected products in very good to excellent yields. Simple and convenient ways to access 4-((ω-mercaptoalkyl) thio)coumarins and the dimeric 4,4′-(alkane-1,4-diylbis(sulfanediyl))bis(coumarins) were also devised with the use of α,ω-alkanedithiols in different ratios with regards to the starting 3-bromocoumarin. The transformation seems to proceed through the DABCO-mediated thia-Michael stereoselective addition of the thiolate anion to the α,β-unsaturated carbonyl system of the coumarin, followed by a DABCO-assisted stereoselective dehydrobromination of the resulting α-bromo carbonyl intermediate. Fil: Mostardeiro, Vitor B.. Universidade Federal de Santa Maria; Brasil Fil: Dilelio, Marina C.. Universidade Federal de Santa Maria; Brasil Fil: Kaufman, Teodoro Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Silveira, Claudio. Universidade Federal de Santa Maria; Brasil

A facile and efficient protocol for the highly selective direct sulfanylation of 3-bromocoumarins under DABCO promotion, was developed. The transformation took place with aromatic and aliphatic thiols as well as with α,ω-dithiols, affording the expected products in very good to excellent yields. Simple and convenient ways to access 4-((ω-mercaptoalkyl) thio)coumarins and the dimeric 4,4'-(alkane-1,4-diylbis(sulfanediyl))bis(coumarins) were also devised with the use of α,ω-alkanedithiols in different ratios with regards to the starting 3-bromocoumarin. The transformation seems to proceed through the DABCO-mediated thia-Michael stereoselective addition of the thiolate anion to the α,β-unsaturated carbonyl system of the coumarin, followed by a DABCO-assisted stereoselective dehydrobromination of the resulting α-bromo carbonyl intermediate.

The present study investigated a possible antidepressant-like effect of ((4-tert-butylcyclohexylidene)methyl) (4-methoxystyryl) sulfide (BMMS) by using the forced swimming test (FST) and the tail suspension test (TST) in Swiss mice. The contribution of serotoninergic, glutamatergic and nitrergic systems in the antidepressant-like activity of BMMS was evaluated. We also examined the involvement of monoamine oxidase (MAO)-A, MAO-B and Na