Revisão química e biológica da tribo Millettiae Miq. (Papilionoideae) e novas contribuições à espécie Deguelia duckeana A.M.G. Azevedo

Abstract

Phytochemical and biological studies of plant constituents enrich both areas of Botany and Biotechnology. In Botany, a chemical character or a strong bioactivity might indicate an evolutionary history. In Biotechnology, this strong bioactivity might become a product. Therefore, our focus in this work was the phytochemical and biological study of tribe Millettieae (Papilionoideae), as a review, and the species Deguelia duckeana (tribe Millettieae), as experimental analysis. From the 45 genera of this tribe, only 17 showed phytochemical study. The most abundant bioactivity founded in this publications are the toxicity to human tumor cell lines (48 antitumoral compounds are listed in this review), followed by the toxicity to arthropods, antibacterial activity and anti-inflammatory action. These potentials are related with the isoflavonoids typical from Millettieae: rotenoids and pterocarpans, as antitumoral and insecticidal, and isoflavones, as anti-inflammatory. The Millettieae constituents possess a toxicity that affects a myriad of life forms, as viruses, bacteria, fungi, protozoa and animals, indicating the broad spectrum of molecular targets its secondary metabolites might achieve. Encouraged by this biological potential and chemical richness, extracts of D. duckeana were evaluated to bioactivities which up to now have been not described in the literature. The dichloromethane extract from roots showed a high toxicity against Mycobacterium tuberculosis and Staphylococcus aureus, at 25 μg/mL. This extract was bacteriostatic against S. aureus and synergic to ciprofloxacin, acting as an efflux pump inhibitor. The hexane extract from leaves also showed an activity against Escherichia coli at 1000 μg/mL. All hexane extracts showed antiangiogenic dose-dependent activity, especially from roots, at 1000 mg/mL, which inhibit 80% the formation of new blood vessels. Therefore, the hexane root extract was submitted to a chromatographic fractionation providing three compounds: derricidin; 3,5,4’-trimethoxystilbene and 4-methoxylonchocarpin. This stilbene is an efflux pump inhibitor in Bacillus cereus and potential antiangiogenic agent, along with 4- methoxylonchocarpin, according to literature.

Deguelia duckeana A.M.G. Azevedo (Tribe Millettieae) is a specie from the Brazilian Amazon Basin described in 1994. Only four biological and chemical studies are found in the literature for this specie. The aim of this study was to investigate antimalarial, antibacterial and antiangiogenic activities from crude extracts and to isolate bioactive substances. All extracts showed no significant antimalarial activity. The most potent antimicrobial was the dichloromethane extract from roots at the concentration of 25 μg.mL-1 against Mycobacterium tuberculosis and Staphylococcus aureus; and at 1000 μg.mL-1, against Enterococcus faecalis and Salmonella enteritidis. This extract was bacteriostatic against S. aureus and acted synergically increasing the activity of ciprofloxacin as an efflux pump inhibitor, more than verapamil. The hexane extract from leaves also showed an activity against Escherichia coli at 1000 μg.mL-1. All hexane extracts have antiangiogenic activity, especially from the roots, inhibiting at 1000 mg.mL-1 more than 80% the formation of blood vessels according to the chick chorioallantoic membrane assay (CAM). The hexane extract from roots was subjected to chromatographic fractionation affording the compounds: derricidine; 3,5,4’- trimethoxystilbene and 4-methoxylonchocarpin, all analysed by 1H and 13C (1D and 2D) Nuclear Magnetic Resonance (NMR) and Mass Spectrometry spectra. The 3,5,4’- trimethoxystilbene and 4-methoxylonchocarpin are potential antiangiogenic agents according to literature.