Fábio Vandresen

Constituintes químicos e avaliação das atividades antibacteriana e antiedematogênica de Aloysia gratissima (Gillies & Hook.) Tronc. e Aloysia virgata (Ruiz & Pav.) Pers., Verbenaceae

Phytochemical study of Aloysia gratissima (Gillies & Hook.) Tronc. e Aloysia virgata (Ruiz & Pav.) Pers., Verbenaceae, afforded fourteen compounds. The structures were established using IR, 1D and 2D NMR and by comparison of its spectroscopic data to those of literature. The antibacterial activity of the crude extract from the leaves and branches and the fractions from the crude extract of A. virgata, besides the isolated compounds hoffmaniacetone, hoffmaniacetone monoacetate, verbascoside and arenarioside were evaluated by means of bioautography and the antiedematogenic activity was evaluated using induced ear oedema model to the crude extracts and methanol fractions for A. gratissima and A. virgata.

Synthesis and evaluation of the trypanocidal activity of a series of 1,3,4-thiadiazoles derivatives of R-(+)-limonene benzaldehyde-thiosemicarbazones

In this study, we synthesized a series of 1,3,4-thiadiazole derivatives of R-(+)-limonene benzaldehyde-thiosemicarbazones (2a–k). We also determined the cytotoxicity in LLCMK2 cells and the activity against epimastigote and trypomastigote forms of Trypanosoma cruzi, of these synthetic compounds and also of a series of 1,3,4-thiadiazole without the monoterpene R-(+)-limonene (4a–k). 1,3,4-Thiadiazole compounds showed significant trypanocidal activity and a high selectivity indexes. The vast majority of the monoterpene derivatives, substituted by R-(+)-limonene, presented better anti-T. cruzi activity than the non-substituted compounds. Regarding the cytotoxic profile, the compounds without the monoterpene R-(+)-limonene were, in general, less toxic. The present findings indicate that the 1,3,4-thiadiazoles derivatives of R-limonene have potential trypanocidal activity that justify further studies to better understand the mechanism of action of these substances on T. cruzi.

Estudo Químico e Avaliação das Atividades Anti-Inflamatória, Antitumoral e Antioxidante das Partes Aéreas de Aeschynomene sensitiva

A especie Aeschynomene sensitiva e considerada uma erva daninha que ocorre principalmente em regioes de clima tropical alagavel, e pode ser encontrada em varios estados brasileiros. Ate o presente momento nao ha relatos na literatura sobre estudo quimico e farmacologico para essa especie. O primeiro estudo fitoquimico de sementes, folhas e galhos de Aeschynomene sensitiva levou ao isolamento do rotenoide glicosilado 6’-hidroxi-6a, 12a-dehidrorotenone, do isoflavonoide glicosilado 2’,7 dihidroxi-4’,5’dimetoxiisoflavona, dos flavonoides quercetina 3-O-β-D-glicosideo, quercetina 3-O-β-D-galactopiranosideo e quercetina-3-O-α-L-ramnopiranosideo, dos compostos fenolicos acido galico e galato de metila e da saponina soiasaponina I.. As estruturas dos compostos isolados foram atribuidas com base em dados espectroscopicos de RMN uni- e bidimensionais e comparacao com dados da literatura. Foram avaliadas as atividades anti-inflamatoria, antitumoral e antioxidantes do extrato metanolico bruto e suas fracoes. As fracoes acetato de etila das sementes (FAcS) e folhas (FAcF) apresentaram elevada atividade antioxidante com IC50 12,4 and 18,2 µg/mL, respectivamente.

Synthesis of novel (-)-Camphene-based thiosemicarbazones and evaluation of anti-Mycobacterium tuberculosis activity

Abstract In this work the aim of study was the synthesis and evaluation of in vitro anti-Mycobacterium tuberculosis activity as well as the cytotoxicity in VERO cells of a series of 17 novel thiosemicarbazones derived from the natural monoterpene (-)-camphene by REMA and MTT methods. Overall, the majority of tested compounds exhibited considerable inhibitory effects on the growth of M. tuberculosis H37Rv, especially the derivatives 3, 4a–c, 4f, 4i, 4k, 5 and 6a–b. MIC values of 20 tested compounds ranged from 3.9 to > 250 μg/mL. It was found that when inserting new nitrogenous groups to the (-)-camphene increased the anti-M. tuberculosis activity of some compounds. The SI was calculated for all compounds that showed highly potent anti-M. tuberculosis activity and the best SI values were 21.36, 26.92 and 31.62 (4b, 6a and 6b), and may be considered potential candidates for future antituberculosis drugs.

4-Fluorobenzaldehyde limonene-based thiosemicarbazone induces apoptosis in PC-3 human prostate cancer cells

Aims: This study evaluated parameters of toxicity and antiproliferative effects of (+)‐N(1)‐4‐fluorobenzaldehyde‐N(4)‐{1‐methyl‐1‐[(1R)‐4‐methylcyclohexene‐3‐il]‐ethyl}‐thiossemicarbazone (4‐FTSC) in PC‐3 adenocarcinoma prostate cells. Main methods: Cytotoxicity of 4‐FTSC in PC‐3 cells was evaluated using MTT assay. Morphology examination of PC‐3 cells treated with 4‐FTSC was also performed as well as the cell death mechanisms induced were investigated using flow cytometry. Parameters of toxicity of 4‐FTSC was conducted by the investigation of its potential myelotoxicity and lymphotoxicity, hemolytic activity and acute oral toxicity profile. Key findings: 4‐FTSC showed promising cytotoxic effects against PC‐3 cells (IC50 = 18.46 &mgr;M). It also triggered apoptotic morphological changes, phosphatidylserine externalization and a significant increase of DNA fragmentation in PC‐3 cells. Moreover, 4‐FTSC did not show changes in the PC‐3 cell cycle with levels of p21, p27, NF&kgr;B and cyclin D1 similar to those found in both control and treated cells. 4‐FTSC also promoted an increase of p53 levels associated with mitochondrial impairment through loss of &dgr;&PSgr;m and ROS overproduction. 4‐FTSC‐induced cell death mechanism in PC‐3 cells involved activation of caspase‐3/‐7 through apoptosis intrinsic pathway via caspase‐9. Regarding toxicological profile, 4‐FTSC showed in vitro lymphotoxicity, although with low cytotoxicity for bone marrow progenitors and no hemolytic potential. Moreover, it was classified as GHS category 5 (LD50 > 2000–5000 mg/Kg), suggesting it has low acute oral systemic toxicity. Significance: 4‐FTSC seems to be a promising candidate to be used as a clinical tool in prostate cancer treatment. Further studies are required to better clarify its toxicopharmacological effects found in this compound.

Chemical Constituents from Leaves of Luehea paniculata

The Luehea genus occurs mainly in tropical climate regions and can be found from the Bahia South until the state of Rio Grande do Sul [1]. Studies have reported that some species belonging to this genus are used as natural remedies to treat rheumatism and haemorrhage [2]. Besides the presence of flavonoids, saponins [3] and triterpenes [4] are the main chemical constituents in species of the Luehea genus. The species Luehea paniculata Mart. is popularly known in Brazil as “acoitacavalo” and used in folk medicine to treat wounds, stomach pain, uterine disorders, hepatitis, and pneumonia [5]. Recently, antifungal and antibacterial properties of the crude extract of Luehea paniculata were reported in the literature [5]. In this context, the absence of phytochemical studies of Luehea paniculata in the literature has become relevant in this study to evaluate the chemical potential of this species present in the Cerrado. The present paper reports the isolation and structural elucidation of six known metabolites from the leaves of Luehea paniculata: -amirin (1) 6 , -amirin-3-acetate (2) 6 , maslinic acid (3) 7 , lupenone (4) 8 , oleanoic acid (5) 6 , and rutin (6) 9 .