Abstract Background Systemic arterial hypertension is a risk factor for cardiac, renal, and metabolic dysfunction. The search for new strategies to prevent and treat cardiovascular diseases led to the synthesis of new N-acylhydrazones to produce antihypertensive effect. Adenosine receptors are an alternative target to reduce blood pressure because of their vasodilatory action and antioxidant properties, which may reduce oxidative stress characteristic of systemic arterial hypertension. Objective To evaluate the antihypertensive profile of novel selenium-containing compounds designed to improve their interaction with adenosine receptors. Methods Vascular reactivity was evaluated by recording the isometric tension of pre-contracted thoracic aorta of male Wistar rats after exposure to increasing concentrations of each derivative (0.1 to 100 μM). To investigate the antihypertensive effect in spontaneously hypertensive rats, systolic, diastolic, and mean arterial pressure and heart rate were determined after intravenous administration of 10 and 30 μmol/kg of the selected compound LASSBio-2062. Results Compounds named LASSBio-2062, LASSBio-2063, LASSBio-2075, LASSBio-2076, LASSBio-2084, LASSBio-430, LASSBio-2092, and LASSBio-2093 promoted vasodilation with mean effective concentrations of 15.5 ± 6.5; 14.6 ± 2.9; 18.7 ± 9.6; 6.7 ± 4.1; > 100; 6.0 ± 3.6; 37.8 ± 11.8; and 15.9 ± 5.7 μM, respectively. LASSBio-2062 (30 μmol/kg) reduced mean arterial pressure in spontaneously hypertensive rats from 124.6 ± 8.6 to 72.0 ± 12.3 mmHg (p < 0.05). Activation of adenosine receptor subtype A3 and potassium channels seem to be involved in the antihypertensive effect of LASSBio-2062. Conclusions The new agonist of adenosine receptor and activator of potassium channels is a potential therapeutic agent to treat systemic arterial hypertension. cardiac renal dysfunction Nacylhydrazones N acylhydrazones properties seleniumcontaining selenium containing precontracted pre contracted 0.1 01 0 1 (0. μM. μM . μM) systolic diastolic 3 μmolkg μmol kg LASSBio2062. LASSBio2062 LASSBio 2062. 2062 LASSBio2062, 2062, LASSBio2063, LASSBio2063 2063, 2063 LASSBio-2063 LASSBio2075, LASSBio2075 2075, 2075 LASSBio-2075 LASSBio2076, LASSBio2076 2076, 2076 LASSBio-2076 LASSBio2084, LASSBio2084 2084, 2084 LASSBio-2084 LASSBio430, LASSBio430 430, 430 LASSBio-430 LASSBio2092, LASSBio2092 2092, 2092 LASSBio-2092 LASSBio2093 2093 LASSBio-209 155 15 5 15. 6.5 65 6 146 14 14. 2.9 29 2 9 187 18 7 18. 9.6 96 67 6. 4.1 41 4 60 3.6 36 378 37 8 37. 11.8 118 11 159 57 5. respectively LASSBio-206 (3 1246 124 124. 86 8. 720 72 72. 123 12 12. p 0.05. 005 0.05 05 0.05) A 0. (0 LASSBio206 206 LASSBio207 207 LASSBio-207 LASSBio208 208 LASSBio-208 LASSBio43 43 LASSBio-43 LASSBio209 209 LASSBio-20 2. 9. 4. 3. 11. ( 00 0.0 LASSBio20 20 LASSBio4 LASSBio-4 LASSBio-2 LASSBio2 LASSBio-

Resumo Fundamento A hipertensão arterial sistêmica é um fator de risco para disfunções cardíacas, renais e metabólicas. A busca por novas estratégias para prevenir e tratar doenças cardiovasculares levou à síntese de novas N-acilidrazonas para produzir efeito anti-hipertensivo. Os receptores de adenosina são um alvo alternativo para reduzir a pressão arterial devido à sua ação vasodilatadora e propriedades antioxidantes, que podem reduzir o estresse oxidativo característico da hipertensão arterial sistêmica. Objetivo Avaliar o perfil anti-hipertensivo de novos compostos contendo selênio desenvolvidos para melhorar sua interação com os receptores de adenosina. Métodos Foi avaliada a reatividade vascular, registrando-se a tensão isométrica da aorta torácica pré-contraída de ratos Wistar machos após exposição a concentrações crescentes de cada derivado (0,1 a 100 μM). Para investigar o efeito anti-hipertensivo em ratos espontaneamente hipertensos, foram determinadas a pressão arterial sistólica, pressão arterial diastólica, pressão arterial média e a frequência cardíaca após administração intravenosa de 10 e 30 μmol/kg do composto selecionado LASSBio-2062. Resultados Os compostos denominados LASSBio-2062, LASSBio-2063, LASSBio-2075, LASSBio-2076, LASSBio-2084, LASSBio-430, LASSBio-2092 e LASSBio-2093 promoveram vasodilatação com concentrações efetivas médias de 15,5 ± 6,5; 14,6 ± 2,9; 18,7 ± 9,6; 6,7 ± 4,1; > 100; 6,0 ± 3,6; 37,8 ± 11,8; e 15,9 ± 5,7 μM, respectivamente. O LASSBio-2062 (30 μmol/kg) reduziu a pressão arterial média em ratos espontaneamente hipertensos de 124,6 ± 8,6 para 72,0 ± 12,3 mmHg (p < 0,05). A ativação do receptor de adenosina subtipo A3 e dos canais de potássio parece estar envolvida no efeito anti-hipertensivo do LASSBio-2062. Conclusões O novo agonista do receptor de adenosina e ativador dos canais de potássio é um potencial agente terapêutico para o tratamento da hipertensão arterial sistêmica. cardíacas metabólicas Nacilidrazonas N acilidrazonas antihipertensivo. antihipertensivo anti hipertensivo. hipertensivo antioxidantes vascular registrandose registrando se précontraída pré contraída 0,1 01 0 1 (0, μM. μM . μM) sistólica diastólica 3 μmolkg μmol kg LASSBio2062. LASSBio2062 LASSBio 2062. 2062 LASSBio2062, 2062, LASSBio2063, LASSBio2063 2063, 2063 LASSBio-2063 LASSBio2075, LASSBio2075 2075, 2075 LASSBio-2075 LASSBio2076, LASSBio2076 2076, 2076 LASSBio-2076 LASSBio2084, LASSBio2084 2084, 2084 LASSBio-2084 LASSBio430, LASSBio430 430, 430 LASSBio-430 LASSBio2092 2092 LASSBio-209 LASSBio2093 2093 155 15 5 15, 6,5 65 6 146 14 14, 2,9 29 2 9 187 18 7 18, 9,6 96 67 6, 4,1 41 4 60 3,6 36 378 37 8 37, 11,8 118 11 159 57 5, respectivamente LASSBio-206 (3 1246 124 124, 86 8, 720 72 72, 123 12 12, p 0,05. 005 0,05 05 0,05) 0, (0 LASSBio206 206 LASSBio207 207 LASSBio-207 LASSBio208 208 LASSBio-208 LASSBio43 43 LASSBio-43 LASSBio209 209 LASSBio-20 2, 9, 4, 3, 11, ( 00 0,0 LASSBio20 20 LASSBio4 LASSBio-4 LASSBio-2 LASSBio2 LASSBio-

No contexto de nossas pesquisas por novos agentes antifúngicos obtidos da flora brasileira, oito extratos e doze frações de Pterogyne nitens Tul., Fabaceae, foram submetidos ao ensaio antifúngico pelo método de microdiluição, contra quatro espécies de fungos oportunistas, Candida albicans, Candida krusei, Candida parapsilosis e Cryptococcus neoformans. Este trabalho revelou que os extratos e frações de P. nitens foram mais ativos contra C. krusei e C. parapsilosis quando comparados a C. neoformans, sendo que o crescimento de C. albicans foi moderadamente afetado por todos os extratos e frações. As atividades mais potentes foram observadas para as frações n-butanólica dos galhos (CIM = 15,6 μg/mL) e raízes (CIM = 31,2 μg/mL) contra C. krusei. Adicionalmente, a fração n-butanólica dos galhos foi submetida ao fracionamento cromatográfico, resultando no isolamento de quatro alcaloides guanidínicos, sendo N-1,N-2,N-3-tri-isopentenilguanidina (1), descrito pela primeira vez em espécies da família Fabaceae e nitensidinas A-C (2-4), os quais apresentaram atividade antifúngica moderada contra C. krusei (CIM = 62,5 μg/mL) e C. parapsilosis (CIM = 31,2 μg/mL).

As part of our ongoing research on antifungal agents from Brazilian flora, eight extracts and twelve fractions from Pterogyne nitens Tul., Fabaceae, were screened for antimicrobial activity against four opportunistic fungi species (Candida albicans, Candida krusei, Candida parapsilosis and Cryptococcus neoformans) using a broth microdilution method. The present investigation reveals that P. nitens extracts and fractions were more effective against C. krusei and C. parapsilosis than against C. neoformans. The growth of C. albicans was moderately affected by all tested extracts and fractions. The strongest effects were observed for n-butanol fractions from branches (MIC = 15.6 μg/mL) and roots (MIC = 31.2 μg/mL) against C. krusei. Additionally, the chromatographic fractionation of the n-butanol fraction from branches afforded four guanidine alkaloids; N-1,N-2,N-3-triisopentenylguanidine (1), described for the first time in the Fabaceae family, and nitensidines A-C (2-4), which showed moderate activity towards C. krusei (MIC = 62.5 μg/mL) and C. parapsilosis (MIC = 31.2 μg/mL).

The phytochemical investigation of the flowers of Pterogyne nitens (Caesalpinioideae) resulted in the isolation and identification of nine phenolic derivatives, quercetin 3-O-sophoroside, taxifolin, astilbin, ourateacatechin, caffeic, ferulic, sinapic, chlorogenic and gallic acid, besides two guanidine alkaloids, pterogynine, pterogynidine. This is the first time these compounds have been reported in P. nitens flowers. As this is a monospecific genus, these secondary metabolites may have taxonomical significance. Their structures were assigned on the basis of spectroscopic analyses, including two-dimensional NMR techniques.

Prostaglandins (PG's), produced from arachidonic acid metabolism, are potent mediators of inflammation. Nonsteroidal anti-inflammatory (NSAIDs) exert their effects by inhibition of prostaglandin endoperoxide synthase (PGHS) enzyme, which catalyses the first committed step in arachidonic acid metabolism. Two isoforms of PGHS are known: PGHS-1, constitutively expressed in most tissues, and is responsible for physiological production of PG's. The second isoform, PGHS-2, is induced by cytokines, mitogens and endotoxins in inflammatory cells, and appears to be responsible for the elevated production of PG's during inflammation. With the recent discovery of the inducible PGHS (PGHS-2), the medicinal chemist now possesses a novel target for designing therapeutic agents that could provide suitable anti-inflammatory activity without the ulcerogenic and renal side effects associated with currently available NSAIDs, all of which inhibit both PGHS-1 and PGHS-2.