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Bioactivity-guided fractionation resulted in the isolation of two new ent-labdane diterpenoids (1-2), along with eighteen known congeners (3-20) from the aerial parts of Andrographis paniculata. Except andrographolide (3) and isoandrographolide (4), eighteen diterpenoids (1-2, 5-20) exhibited potent anticomplement activity with the CH50 and AP50 values of 23.1-638.3 µg/mL and 54.2-603.9 µg/mL, respectively. The structure-activity relationships of the isolates showed that 14-dehydroxylation, glycosidation and the opening of lactone were essential for anticomplement activity. Although inactive, andrographolide (3) was successfully transformed to anticomplement compounds (5 and 10) in vitro by human fecal bacteria, indicating that this major ent-labdane diterpenoid of A. paniculata might also exhibit anticomplement activity in vivo through their potential active metabolites. The targets of several bioactive ent-labdane diterpenoids in complement activation cascade were identified as well.

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Eleven new ent-labdane diterpenoids, cheodontoins A-K (1-11), and thirteen known diterpenoids involving two ent-labdanes (12-13) and eleven ent-kauranes (14-24), were isolated from the active part of Chelonopsis odontochila (Lamiaceae) under the guidance of bioassay. The structures of cheodontoins A-K (1-11) were elucidated by extensive HRESIMS, 1D and 2D NMR, [α]D and ECD experiments, X-ray diffraction and quantum calculation. Interestingly, five nor-ent-labdanes (9-13) were obtained from this genus for the first time. One ent-labdane diterpenoid (12) and four ent-kaurane diterpenoids (16, 19, 23, and 24) showed α-glucosidase inhibitory activity with IC50 values of 326.5 ± 3.5, 599.1 ± 13.8, 620.1 ± 16.1, 185.0 ± 4.2, and 190.7 ± 11.6 µM, respectively. Compounds 12 and 16 were α-glucosidase mixed-type inhibitors with Ki values of 334.1 and 589.2 µM according to the enzyme kinetics using Lineweaver-Burk and Dixon plots. Docking study manifested that compounds 12 and 23 well located in the catalytic pocket of α-glucosidase by hydrophobic effects with Trp1355, Trp1369, Phe1427, Phe1559, and Phe1560 residues. This study provides new insights for the antidiabetic effects of C. odontochila with ent-labdane and ent-kaurane diterpenoids as the active constituents.

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Twelve new ent-labdane diterpenoids, hypofolins A - F (1 - 6) and hypofolins G - L (7a/7b, 8a/8b, and 9a/9b), were isolated from the roots of Hypoestes phyllostachya 'Pink Splash'. Their structures were elucidated by extensive 1D- and 2D-NMR spectroscopic and HR-MS data. The absolute configurations of 1, 2, 5, and 7a/7b were determined by single crystal X-ray diffraction and ECD analysis, as well as chemical transformations. Compounds 7a/7b, 8a/8b, and 9a/9b were isolated as three pairs of interconverting mixture of two isomers between ketone and hemiketal types. Compound 1 showed weak cytotoxicity against SMMC-7721 cell line with IC50 value of 31.40 µm.

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Pressurised hot water extraction (PHWE) was employed to effect the extraction of two carboxylic acid-containing ent-labdane diterpenoids from Dodonaea viscosa. The different extraction profile provided by PHWE in this case suggests that this recently developed method also has applications as a complementary tool for natural products extraction.

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The objective of this study was to evaluate the larvicidal activity of diterpenoids obtained from the oil-resin of Copaifera reticulata against Aedes aegypti larvae, the principal vector of dengue and urban yellow fever. Four diterpenes were obtained from oil-resin extraction with organic solvents and subsequent chromatographic and spectroscopic procedures allowed to isolation and identification of these compounds as 3-b-acetoxylabdan-8(17)-13-dien-15-oic acid (1), alepterolic acid (2), 3-b-hidroxylabdan-8(17)-en-15-oic acid (3), and ent-agatic acid (4). Each compound was previously dissolved in dimethylsulphoxide, and distilled water was added to obtain the desired concentrations. Twenty larvae of third instars were placed into plastic beckers, containing the solution test (25 mL), in a five repetitions scheme, and their mortality, indicated by torpor and darkening of the cephalic capsule, was recorded after 48h. Probit analyses were used to determine lethal concentrations (LC50 and LC90) and their respective 95 percent confidence intervals. This study showed that only diterpenoids 1 and 2 exhibited larvicidal properties with LC50 of 0.8 ppm and 87.3 ppm, respectively, revealing the former as the most toxic compound against third instars of Ae. aegypti. Therefore, this compound seems to be an interesting source for new metabolite to be exploited.

O objetivo deste trabalho foi avaliar a atividade larvicida de diterpenos isolados do óleo-resina de Copaifera reticulata sobre Aedes aegypti, principal vetor de dengue e febre amarela urbana. Quatro diterpenóides foram obtidos a partir da extração do óleo-resina com solventes orgânicos e, subseqüentes procedimentos cromatográficos e espectroscópicos permitiram o isolamento e a identificação desses compostos como ácido 3-b-acetoxylabdan-8(17)-13-dien-15-óico (1), ácido alepterólico (2), ácido 3-b-hidroxylabdan-8(17)-en-15-óico (3) e ácido ent-agático (4). Cada um desses compostos foi previamente solubilizado em dimetilsulfóxido, acrescentando-se água, até se obterem as concentrações desejadas. Em cada bioensaio foram utilizadas 20 larvas de 3° estádio de Ae. aegypti colocadas em 25 mL da solução-teste. Foram feitas cinco repetições, e a mortalidade avaliada 48 h após a exposição, indicada pela ausência de movimentos e escurecimento da cápsula cefálica. Os dados obtidos da mortalidade x concentração (ppm) foram analisados, em gráfico de Probit para avaliar as concentrações letais (CL50 e CL90). Este estudo revelou que os diterpenóides 1 e 2 mostraram atividade larvicida com CL50 de 0,8 e 87,3 ppm, respectivamente, sendo o diterpeno 1 o composto mais promissor a ser usado como larvicida para o controle de Ae. aegypti.

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