Antiplasmodial activity of iron(II) and ruthenium(II) organometallic complexes against Plasmodium falciparum blood parasites

This work reports the in vitro activity against Plasmodium falciparumblood forms (W2 clone, chloroquine-resistant) of tamoxifen-based compounds and their ferrocenyl (ferrocifens) and ruthenocenyl (ruthenocifens) derivatives, as well as their cytotoxicity against HepG2 human hepatoma cells. Surprisingly with these series, results indicate that the biological activity of ruthenocifens is better than that of ferrocifens and other tamoxifen-like compounds. The synthesis of a new metal-based compound is also described. It was shown, for the first time, that ruthenocifens are good antiplasmodial prototypes. Further studies will be conducted aiming at a better understanding of their mechanism of action and at obtaining new compounds with better therapeutic profile.

Fontes de obtenção de medicamentos para tratamento de hipertensão arterial no Brasil: análise da Pesquisa Nacional de Saúde, 2013 / Sources for obtaining drugs for hypertension in Brazil: results from the National Health Survey, 2013

RESUMO: Objetivo: Analisar as diferenças sociodemográficas dos indivíduos adultos hipertensos, em relação às fontes de obtenção de medicamentos para tratar hipertensão arterial no Brasil. Métodos: Análise secundária dos dados oriundos da Pesquisa Nacional de Saúde, 2013; os desfechos considerados nas análises foram representados pelas fontes de obtenção de medicamentos para tratar a hipertensão arterial. Resultados: Foram entrevistados 10.017 indivíduos. A grande maioria dos hipertensos em uso de medicamentos (74,0%) utiliza uma fonte única de obtenção de medicamentos 7,3% (IC95% 6,4 - 8,4) referiu obter todos os medicamentos por meio dos planos de saúde privados; 22,7% (IC95% 21,0 - 24,4) em farmácias do sistema público de saúde; 21,8% (IC95% 20,2 - 23,4) no Programa Farmácia Popular do Brasil; e 29,5% (IC95% 27,7 - 31,4) exclusivamente pelas farmácias comerciais. A obtenção no sistema público de saúde como fonte única diminuiu com o avanço da idade, apresentou-se menor nas pessoas de cor da pele branca, diminuiu fortemente com o aumento da escolaridade e evidenciou-se menor entre os residentes na região Norte do país; no Programa Farmácia Popular do Brasil, a fonte única de obtenção também foi menor para as pessoas com maior escolaridade. A obtenção nas farmácias comerciais esteve associada positivamente com um perfil do sexo masculino, de maior escolaridade, de idade mais elevada, tendo declarado cor da pele branca. A ocorrência de mais de uma fonte de obtenção mostrou-se associada positivamente ao aumento da idade e inversamente ao aumento da escolaridade. Conclusões: Os resultados possibilitaram identificar diferentes estratégias para obtenção de medicamentos usados no tratamento da hipertensão, de modo a explicar como são obtidos os medicamentos no país e qual o impacto das políticas públicas nesse setor.

ABSTRACT: Objective: To analyze the sociodemographic differences among adults with hypertension regarding the sources for obtaining drugs for hypertension treatment in Brazil. Methods: This is a secondary analysis of data from the National Health Survey 2013; the outcomes considered for the analysis were the sources for obtaining drugs for treating high blood pressure. Results: The great majority (74%) of patients with hypertension taking drugs use a single source for obtaining them, 7.3% (95%CI 6.4 - 8.4) reported getting all the drugs through private health plans, 22.7% (95%CI 21.0 - 24.4) by pharmacies of the public health system, 21.8% (95%CI 20.2 - 23.4) by the Popular Pharmacy Program, and about one-third (29.5%; 95%CI 27.7 - 31.4) exclusively by commercial pharmacies. Having the public health system as the single source for obtaining the drugs was found to decrease with age, was lower in white people, decreased strongly with increase in education, and was lower for residents in the North region. Exclusive obtainment through the Popular Pharmacy Program was lower for people with higher education. Obtainment in commercial pharmacies was positively associated with being male, with higher education level, being older, and having white skin color. Obtainment using more than one source was positively associated with increasing age and inversely associated with higher education levels. Conclusions: The results allowed the identification of a trajectory of patients in obtaining drugs for the treatment of hypertension, aiming at explaining how the drugs are obtained and the impact of public policies in this sector in the country.

New nitric oxide donors based on ruthenium complexes

Nitric oxide (NO) donors produce NO-related activity when applied to biological systems. Among its diverse functions, NO has been implicated in vascular smooth muscle relaxation. Despite the great importance of NO in biological systems, its pharmacological and physiological studies have been limited due to its high reactivity and short half-life. In this review we will focus on our recent investigations of nitrosyl ruthenium complexes as NO-delivery agents and their effects on vascular smooth muscle cell relaxation. The high affinity of ruthenium for NO is a marked feature of its chemistry. The main signaling pathway responsible for the vascular relaxation induced by NO involves the activation of soluble guanylyl-cyclase, with subsequent accumulation of cGMP and activation of cGMP-dependent protein kinase. This in turn can activate several proteins such as K+ channels as well as induce vasodilatation by a decrease in cytosolic Ca2+. Oxidative stress and associated oxidative damage are mediators of vascular damage in several cardiovascular diseases, including hypertension. The increased production of the superoxide anion (O2-) by the vascular wall has been observed in different animal models of hypertension. Vascular relaxation to the endogenous NO-related response or to NO released from NO deliverers is impaired in vessels from renal hypertensive (2K-1C) rats. A growing amount of evidence supports the possibility that increased NO inactivation by excess O2- may account for the decreased NO bioavailability and vascular dysfunction in hypertension.