Phytochemical study and antimicrobial activity evaluation of Talauma ovata

O estudo fitoquímico de cascas do tronco e folhas de Talauma ovata St. Hil. (Magnoliaceae) levou ao isolamento das lactonas sesquiterpênicas costunolídeo e partenolídeo e dos alcalóides aporfínicos liriodenina, lanuginosina, dicentrinona, O-metilmoschatolina e N-acetilxilopina. Os extratos brutos, frações de extratos obtidas por partição com solventes e substâncias isoladas foram avaliadas pelo método de difusão em ágar, utilizando-se 15 bactérias Gram-positivas, 3 bactérias Gram-negativas e 3 fungos. A maior atividade foi detectada na fração em diclorometano do extrato em etanol das cascas, a qual foi ativa contra bactérias Gram-positivas. Nenhum extrato ou fração inibiu o crescimento de bactérias Gram-negativas ou fungos. Partenolídeo e O-metilmoschatolina apresentaram boa atividade contra várias cepas de Staphylococcus aureus, com concentração inibitória mínima (CIM) variando entre 100 e 25 μg/mL. O alcalóide Nacetilxilopina apresentou moderada atividade antifúngica (CIM = 250 μg/mL). Liriodenina, lanuginosina, dicentrinona e O-metilmoschatolina estão sendo descritos pela primeira vez nesta espécie.Petroleum ether and ethanol extracts of trunk bark and leaves from Talauma ovata St. Hil. (Magnoliaceae) were submitted to chromatographic separation. This procedure furnished the sesquiterpene lactones costunolide and parthenolide and the aporphine alkaloids liriodenine, lanuginosine, dicentrinone, O-methylmoschatoline and N-acetylxylopine. Crude extracts, fractions from sequential partition with solvents and isolated compounds were screened against 15 Gram-positive bacteria, 3 Gram-negative bacteria and 3 yeasts, using the agar well-diffusion technique. The most activity was detected in the fraction in dichloromethane from ethanol extract of trunk bark, which was active against Gram-positive bacteria, but not against Gram-negative bacteria or fungi. Parthenolide and O-methylmoschatoline showed good and specific activity against several strains of Staphylococcus aureus, with minimum inhibitory concentration (MIC) varying from 100 to 25 μg/mL. The alkaloid N-acetylxylopine exhibited moderate activity against Candida albicans (MIC = 250 μg/mL). This is the first report of liriodenine, lanuginosine, dicentrinone and O-methylmoschatoline in T. ovataColegio de Farmacéuticos de la Provincia de Buenos Aire

Antiplasmodial activity of synthetic ellipticine derivatives and an isolated analog

Ellipticine has been shown previously to exhibit excellent in vitro antiplasmodial activity and in vivo antimalarial properties that are comparable to those of the control drug chloroquine in a mouse malaria model. Ellipticine derivatives and analogs exhibit antimalarial potential however only a few have been studied to date. Herein, ellipticine and a structural analog were isolated from Aspidosperma vargasii bark. A-ring brominated and nitrated ellipticine derivatives exhibit good in vitro inhibition of Plasmodium falciparum K1 and 3D7 strains. Several of the compounds were found not to be toxic to human fetal lung fibroblasts. 9-Nitroellipticine (IC50 = 0.55 μM) exhibits greater antiplasmodial activity than ellipticine. These results are further evidence of the antimalarial potential of ellipticine derivatives. © 2014 Elsevier Ltd. All rights reserved

Comparative in vitro and in vivo antimalarial activity of the indole alkaloids ellipticine, olivacine, cryptolepine and a synthetic cryptolepine analog

Indole alkaloids ellipticine (1), cryptolepine triflate (2a), rationally designed 11-(4-piperidinamino)cryptolepine hydrogen dichloride (2b) and olivacine (3) (an isomer of 1) were evaluated in vitro against Plasmodium falciparum and in vivo in Plasmodium berghei-infected mice. 1-3 inhibited P. falciparum (IC50 ≤ 1.4 μM, order of activity: 2b > 1 > 2a > 3). In vitro toxicity to murine macrophages was evaluated and revealed selectivity indices (SI) of 10-12 for 2a and SI > 2.8 × 102 for 1, 2b and 3. 1 administered orally at 50 mg/kg/day was highly active against P. berghei (in vivo inhibition compared to untreated control (IVI) = 100%, mean survival time (MST) > 40 days, comparable activity to chloroquine control). 1 administered orally and subcutaneously was active at 10 mg/kg/day (IVI = 70-77%; MST = 27-29 days). 3 exhibited high oral activity at ≥50 mg/kg/day (IVI = 90-97%, MST = 23-27 days). Cryptolepine (2a) administered orally and subcutaneously exhibited moderate activity at 50 mg/kg/day (IVI = 43-63%, MST = 24-25 days). At 50 mg/kg/day, 2b administered subcutaneously was lethal to infected mice (MST = 3 days) and moderately active when administered orally (IVI = 45-55%, MST = 25 days). 1 and 3 are promising compounds for development of antimalarials. © 2012 Elsevier GmbH