Green Synthesis of Molecules for the Treatment of Neglected Diseases.

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.

Contribution of serotonergic and nitrergic pathways, as well as monoamine oxidase-a and Na+, K+-ATPase enzymes in antidepressant-like action of ((4-tert-butylcyclohexylidene) methyl) (4-methoxystyryl) sulfide (BMMS).

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.

Efficient synthesis of 4-sulfanylcoumarins from 3-bromo-coumarins via a highly selective DABCO-mediated one-pot thia-Michael addition/elimination process.

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,ß-unsaturated carbonyl system of the coumarin, followed by a DABCO-assisted stereoselective dehydrobromination of the resulting α-bromo carbonyl intermediate.