Aristolochia triangularis Cham.: análise fitoquímica, atividades antimicrobiana, antimicobacteriana e de inibição enzimática

Abstract

The genus Aristolochia is widely used in folk medicine because of its detoxifying, anesthetic and antiviral properties. In Brazil, the species Aristolochia triangularis Cham., popularly known as "cipó mil-homens", is used as antipyretic, antiseptic, sedative, antiofidic and anti-inflammatory. Studies report the isolation of alkaloids, tannins, lignans and terpenes of A. triangularis. Among the diseases that bring global health concerns are disorders of the central nervous system and infectious diseases. Depression, schizophrenia and Alzheimer's disease do not heal until today, and their symptoms are alleviated through various therapies. However, due to the adverse effects and toxicity of the drugs available in the clinic, the search for new active substances to treat these diseases is extremely important. It is known that the enzymes acetylcholinesterase (AChE) and prolyl oligopeptidase (POP) have their altered levels in these disorders. Infectious diseases, due to the indiscriminate use of antimicrobials by the population, have become a serious problem, especially for immunocompromised patients. The multiresistance of the microorganisms against the already known treatments makes the research for new drugs gain relevance. Considering that medicinal plants have many compounds still unknown in their potentials, this work aimed to prepare extracts and fractions of A. triangularis, isolate and identify their secondary metabolites, evaluate the inhibitory activity against AChE and POP enzymes, and evaluate the activities antimicrobial and antimycobacterial properties of extracts, fractions and isolated pure substances. As a result, nine isolated compounds were obtained, among them three diterpenes (ent-Kaur-16-en-19-al (1), (-)-Kaur-16-en-19-oic acid (4) dihydrocubebin (6), α and β-cubebin (7a + 7b)), a sequiterpene (nerolidol (3)) and an alkaloid ( aristolactam BII (8)). The oxime derivative 9 was also obtained from diterpene (1). The antimicrobial potential of the isolated compounds was studied, showing that compound (4) was the most active in the inhibition of the bacteria tested, mainly against Shigella sonnei. This diterpene also had excellent bacteriostatic and bactericidal activity (MIC/MLC - 3.1 / 6.2 μg/mL) against Enterobacter aerogenes. The highest antifungal activity was observed against Candida krusei, where compounds 4 and 8 significantly inhibited fungal growth (MIC - 6.2 μg/mL). All extracts, fractions and substances tested had an important antimycobacterial potential, especially against Mycobacterium abscessus. The compound nerolidol (3) showed the highest inhibition activity of the mycobacteria tested (MIC of 4.9-19.9 μg/mL). The AChE assays demonstrated a good enzyme inhibition result by the ethereal acid fraction, with 48% inhibition at the concentration of 200 μg/mL. Compared to POP, A. triangularis extract and fractions showed high inhibition capacity, with values of 70-92% (at 200 μg/mL). Among the isolated compounds, dihydrocubebin (6) showed higher inhibitory activity of this enzyme (150 μg/mL), presenting IC50 of 15.2 ± 0.5 μM.