Natural Phenolic Compounds with Antithrombotic and Antiplatelet Effects: A Drug-likeness Approach.

BACKGROUND: Thrombosis is one of the major causes of morbidity and mortality in a wide range of vessel diseases. Several studies have been conducted to identify antithrombotic agents from medicinal plants, and phenolic compounds (PCs) have been shown to effectively inhibit plasma coagulation and platelet aggregation. OBJECTIVES: This study aimed to conduct a survey of the natural PCs with proven antithrombotic and antiplatelet activities, as well as to evaluate by computational modeling the physicochemical and toxicological properties of these compounds using drug-likeness approaches. METHODS: The data were collected from the scientific database: 'Web of Science', 'Scifinder', 'Pubmed', 'ScienceDirect' and 'Google Scholar', the different classes of PCs with antithrombotic or antiplatelet effects were used as keywords. These molecules were also evaluated for their Drug-Likeness properties and toxicity to verify their profile for being candidates for new antithrombotic drugs. RESULTS: In this review, it was possible to register 85 lignans, 73 flavonoids, 28 coumarins, 21 quinones, 23 phenolic acids, 8 xanthones and 8 simple phenols. Activity records for tannins were not found in the researched databases. Of these 246 compounds, 213 did not violate any of Lipinski's rules of five, of which 125 (59%) showed non-toxicity, being promising candidates for new potential antithrombotic drugs. CONCLUSION: This review arouses interest in the isolation of phenolic compounds that may allow a new approach for the prevention of both arterial and venous thrombosis, with the potential to become alternatives in the prevention and treatment of cardiovascular diseases.

Ovicidal, pupicidal, adulticidal, and repellent activity of Helicteres velutina K. Schum against Aedes aegypti L. (Diptera: Culicidae).

Aedes aegypti is a vector of emerging and neglected diseases, such as dengue, chikungunya, and Zika. Helicteres velutina, known as "pitó" in Brazil, is traditionally used as an insect repellent, and several studies have demonstrated its larvicidal activity. The aim of this study was to investigate this species and evaluate its potential ovicidal, pupicidal, adulticidal, and repellent activity. The viability of the eggs was evaluated using different concentrations of the test substances for 25 days. The hexane fraction killed 72.7% of the eggs, while dichloromethane killed 67.7%. The survival of the pupae and adults was verified after 72 h and 48 h, respectively. The LC50 for the hexane and dichloromethane fractions was 0.12 mg/mL and 8.85 mg/mL for pupae, 8.01 mg/mL and 0.74 mg/mL for adults (tarsal test), and 0.05 mg/mL and 0.23 mg/mL for adults (body test), respectively. Repellency was assessed for 240 min using neonatal Wistar rats on a Y-tube olfactometer. The hexane fraction attracted mosquitoes to the test chamber, while the dichloromethane fraction had a repellent action. The 7,4'-di-O-methyl-8-O-sulfate flavone provides greater repellency, and this finding is similar to the results of the in silico studies that have shown the potential of this substance against adult mosquitoes. This suggests that 7,4'-di-O-methyl-8-O-sulfate flavone may be one of the substances present in the extract from aerial parts of H. velutina that is responsible for the repellent activity mentioned in traditional medicine. These findings provide a better understanding of the insecticidal and repellent activity of the extract, fraction, and compounds isolated from H. velutina against Ae. aegypti, thereby revealing its potential in the development of a more effective botanical insecticide.

Aedes aegypti é o vetor de doenças emergentes e negligenciadas, como dengue, chikungunya e Zika. Helicteres velutina, conhecida como 'pitó' no Brasil, é tradicionalmente usada como um repelente de insetos, estudos anteriores comprovaram sua atividade larvicida. O objetivo desta pesquisa foi investigar esta espécie, avaliando seu potencial ovicida, pupicida, adulticida e repelente. A viabilidade dos ovos foi avaliada utilizando diferentes concentrações das substâncias teste durante 25 dias, a fração hexano causou a inviabilização de 72,7% dos ovos, enquanto a diclorometano matou 67,7%. A sobrevivência de pupas e adultos foi verificada após 72 e 48 horas, respectivamente. A CL50 da fração hexano e diclorometano foi de 0,12 e 8,85 mg/mL para pupas; 8,0 e 0,74 mg/mL para adultos (teste tarsal); 0,05 e 0,23 mg/mL para adultos (teste corporal), respectivamente. A repelência foi avaliada durante 240 min utilizando neonatos de ratos Wistar em um olfatômetro de tubo Y. No teste de atração-repelência, a fração hexano atraiu mosquitos para camara teste, enquanto a fração diclorometano causou repelência. A 7,4'-di-O-metil-8-O-sulfato flavona proporcionol maior repelência, corroborando com estudos in silico que mostram potencial dessa substância em mosquitos adultos. Sugerindo que 7,4'-di-O-metil-8-O-sulfato flavona pode ser uma das substâncias presente no extrato das partes aéreas de H. velutina, responsável pela atividade repelente citada na medicina tradicional. Esses achados proporcionam uma melhor compreensão da atividade inseticida e repelente do extrato, fração e compostos isolados de H. velutina frente a Ae. aegypti mostrando potencial no desenvolvimento de um inseticida botânico mais eficaz.