Copaifera species (Fabaceae) comprises approximately 70 species of large trees, from which 16 can be found in Brazil. The oleoresins obtained from their trunk are widely used in Brazilian folk medicine, which display important antitumoral potential. Chemically, these oleoresins are mainly composed of a mixture of sesquiterpenes and diterpenes. In this paper we are describing the isolation and identification of 12 already known terpenes from oleoresins obtained from three different Copaifera species (C. multijuga, C. pubiflora and C. trapezifolia) and 2 novel diterpenes (ent-16-hidroxy-3,13 clerodadien-15,18-dioic acid and ent-labda-5,13-dien-15-oic acid) from C. trapezifolia. Both new compounds were identified by nuclear magnetic resonance (NMR) spectroscopic (1H and 13C NMR, correlation 1H-1H (COSY), heteronuclear multiple quantum coherence (HMQC) and heteronuclear multiple bond correlation (HMBC)) and by high-resolution electrospray ionization mass spectrometry (HR-ESIMS) analyses. The cytotoxic potential of these oleoresins, their main non-volatile compounds and their volatile compound fractions were evaluated against a panel of tumoral (MCF-7, ACP01, A549, HeLa) and normal cell lines (MCF-10A, GM07492-A) through XTT (tetrazolium salt) and SRB (sulforhodamine B) assays. The novel diterpene ent-labda-5,13-dien-15-oic acid displayed relevant cytotoxic effect against most of the cancer cell lines with mean inhibitory concentration (IC50) values ranging from 3.57 ± 1.12 to 22.56 ± 1.03 µg mL-1, and a high selectivity level in both assays.

In this work, a search for antimicrobial agents against multi-drug resistant (MDR) bacteria was undertaken. It involved two natural diterpenes of different basic skeletons, named ent-kaurenoic acid and ent-pimaradienoic acid, that were used as precursors to access 28 semi-synthetic derivatives that were also submitted to biological assays. All 30 substances were assayed against a set of seven clinically isolated MDR bacteria, including three Staphylococcus aureus strains. Results classified both natural compounds as promising bactericidal antimicrobial agents against these MDR bacteria, especially for their performance in time-kill curve assay, improving on the positive control vancomycin. Moreover, di-hydro ent-pimaradienoic acid, obtained as one of the derivatives, also displayed promising minimum inhibitory concentration (MIC) values against the microorganism set, proving optimum activity against S. aureus strains. Thereby, this work also yielded a promising semi-synthetic bacteriostatic antimicrobial agent against MDR S. aureus. Furthermore, the study was carried out with 30 structures in order to verify the veracity and scope of Urzúa’s hypothesis about the structure-activity relationship between diterpenes and antimicrobial action. Our results are 93% in agreement with this hypothesis.

In this paper we screened the dichloromethane extract from the aerial parts of Salvia officinalis L., Lamiaceae, against a representative panel of microorganisms that cause caries, conducted a bioassay-guided fractionation to establish themselves the most active metabolite (manool) and determined the Salvia officinalis fraction with the manool highest concentration to be used to activate an ingredient in oral care products such as toothpastes and mouthwashes. Both manool and S. officinalis extract showed very promising minimal inhibitory concentration values (between 6.24 and 31.36 µg.ml-1) and time kill curves against the primary causative agents of dental caries (Streptococcus mutans) revealed that, at twice its minimal bactericidal concentration (12.48 µg.ml-1), manool required 6 h to completely kill the bacteria. Salvia officinalis extract at twice its minimal bactericidal concentration (31.36 µg.ml-1) needed 12 h. The results achieved with Salvia officinalis extract motivated us to develop and validate an analytical RP-HPLC method to detect and determine manool in this extract. The validation parameters were satisfactorily met and evaluated allows us to consider the developed method suitable for use in different labs. In conclusion, our results evidenced that the manool-rich S. officinalis extract can be considered an analytically validated alternative to develop novel and effective antimicrobial agents against the main bacteria responsible for dental caries.

Pterogyne nitens (Fabaceae-Caesalpinioideae) é uma árvore nativa da América do Sul, onde é empregada na medicina popular para o tratamento da ascaridíase. Recentemente, descrevemos o efeito mutagênico do extrato etanólico das folhas de P. nitens. Dessa forma, o presente estudo teve por objetivo aprofundar a avaliação do potencial mutagênico das frações isoladas das folhas de Pterogyne nitens, acetato de etila (AcOEt), n-butanólica (BuOH) e hidroalcóolica (HA). Quando o efeito mutagênico foi observado somente nas maiores concentrações testadas, o potencial antimutagênico também foi avaliado. Os ensaios mutagênicos e antimutagênicos foram realizados utilizando ensaio de micronúcleo em Trandescantia pallida. Na avaliação de mutagenicidade, observou-se o efeito nas frações AcOEt (0,460 mg/mL), BuOH (0,142, 0,285, 0,570 e 1,14 mg/mL) e HA (0,050, 0,100, 0,200 e 0,400 mg/mL). Considerando que o efeito mutagênico da fração AcOEt foi observado somente na concentração mais elevada (0,460 mg/mL), o potencial antimutagênico da mesma foi avaliado. As concentrações de 0,115 e 0,230 mg/mL da fração AcOEt demonstraram atividade antimutagênica. A partir dos resultados do presente estudo, conclui-se que determinadas frações de P. nitens apresentam mutagenicidade (BuOH e HA), enquanto a fração AcOEt apresentou efeito antimutagênico nas maiores concentrações. Esses resultados tornam o estudo da P. nitens bastante promissor, considerando que esta planta possui distribuição geográfica ampla e tem sido pouco estudada.

Pterogyne nitens (Fabaceae-Caesalpinioideae) is a tree native to South American, where it is used in folk treatment of ascaridiasis. Recently, we have been describing the mutagenic effect of the ethanol extract of leaves of P. nitens. Thus, the present study aimed at evaluating the mutagenic potential of the ethyl acetate (EtOAc), n- butanol (BuOH) and hydroalcoholic (HA) fractions. When the mutagenic effect was observed only in the highest tested concentrations, the antimutagenic activity was also evaluated. Both mutagenic and antimutagenic assays were performed using T. pallida micronuclei assay. Mutagenicity was observed between different concentrations of the P nitens fractions, EtOAc (0.460 mg/mL), BuOH (0.142, 0.285, 0.570 and 1.14 mg/mL) and HA (0.050, 0.100, 0.200 and 0.400 mg/mL). Whereas the mutagenic effect of the EtOAc fraction was observed in the highest concentration (0.460 mg/mL), its antimutagenic potential was evaluated. The 0.115 and 0.230 mg/mL concentrations of the EtOAc fraction demonstrated antimutagenic activity. Based on the results of the present study we can conclude that some P. nitens fractions (BuOH and HA) demonstrated mutagenic effects whereas the EtOAc fraction shown low mutagenicity and amtimutagenicity in the two higher concentrations. Those results stimulate the studies with P. nitens, which possess spread geographic distribution and it is still low studied.