ABSTRACT The organic extracts from stems, roots and leaves of Tephrosia egregia Sandwith, Fabaceae, provided a new flavone, 5-hydroxy-8-(1",2"-epoxy-3"-hydroxy-3"-methylbutyl)-7-methoxyflavone (1), in addition to eleven known compounds: pongaflavone (2), praecansone B (3), 12a-hydroxyrotenone (4), praecansone A, 2',6'-dimethoxy-4',5'-(2",2"-dimethyl)-pyranochalcone, pongachalcone, maackiain, β-sistosterol and its glucoside, p-cumaric acid and cinnamic acid. The structures of all compounds were established on the basis of spectroscopic methods, mainly 1D and 2D NMR and HRESIMS, involving comparison with literature data. Cytotoxicity of compounds 1–4 was evaluated against AGP-01 (cancerous ascitic fluid), HCT-116 (colon adenocarcinoma), HL-60 (leukemia), PC-3 (prostate carcinoma), SF-295 (glioblastoma) and SKMEL 28 (melanoma) cell lines.

Five new diterpenes derivatives named as ornatin A, B, C, D and E, in addition to six known related diterpenes were isolated from the aerial parts of cultivated specimens of Plectranthus ornatus. The structures were elucidated using a combination of 1D/2D nuclear magnetic resonance (NMR) spectroscopy, high-resolution electrospray ionization mass spectrometry (HRESIMS) and comparison with published NMR data of analogous compounds. All isolated compounds were assayed against four human cancer cell lines, and Gram-positive and Gram-negative bacteria strains. None of them showed any cytotoxic activity, but ornatin C, D, E and three related diterpenes displayed marginal bactericidal or bacteriostatic effects against the Gram-positive strains.

One new alkaloid, 2α-10bα-dihydroxy-9-O-demethylhomolycorine, in addition to seven others known alkaloids, and 5-(hydroxymethyl)furfural, piscidic acid and eucomic acid, were isolated from the bulbs of Hippeastrum solandriflorum. The structures of all compounds were determined using nuclear magnetic resonance (NMR) spectroscopic techniques: 1H NMR and 13C NMR, heteronuclear single quantum coherence (HSQC), heteronuclear multiple bond correlation (HMBC), nuclear Overhauser effect spectroscopy (NOESY), and also the high-resolution electrospray ionization mass spectrometry (EI-HRMS). The cytotoxic activity of all alkaloids was evaluated against three human cancer cell lines (HCT-116, HL-60, OVCAR8 and SF-295) showing IC50 values ranging from 0.01 to 35.7 µM.

O presente estudo descreve a acentuada atividade citotóxica da nor-β-lapachona, seus derivados arilamino substituídos, naftoquinonas iodadas e metilada, além de nor-β-lapachonas 1,2,3-triazólicas, contra quatro linhagens de células de leucemia humana (HL-60, K562, Molt-4 e Jurkat). Nor-β-lapachonas arilamino substituídas foram identificadas com potente atividade, revelando-se como potenciais protótipos contra as linhagens tumorais descritas. Estudos utilizando o ensaio cometa evidenciaram danos ao ácido desoxirribonucleico (ADN) causado pelos derivados arilamino substituídos devido o aumento dos níveis intracelulares de espécies reativas de oxigênio (ERO's). Células de HL-60 foram selecionadas para a continuidade dos estudos de mecanismos moleculares subjacentes e apoptose induzida pelos derivados quinoidais foi observada por análise de citometria de fluxo. Cepas de Saccharomyces cerevisiae foram utilizadas para uma investigação preliminar sobre o mecanismo de ação em topoisomerases de ADN. Os estudos sugerem que, aparentemente, a citotoxidade dos compostos não envolve a inibição de topoisomerases, mas que o tratamento prejudica a atividade de reparação do ADN, provocando assim a morte celular. A capacidade em induzir apoptose e aberrações cromossômicas em fibroblastos de pulmão de hamster chinês (células V79) também foi investigada. Núcleos apoptóticos foram observados e nossos estudos indicam uma correlação entre dano ao ADN e apoptose.

The current study describes that nor-β-lapachone and its arylamino derivatives, iodinated and methylated naphthoquinones and nor-β-lapachone-based 1,2,3-triazoles exhibited pronounced cytotoxic effects against four human leukemia cell lines (HL-60, K562, Molt-4 and Jurkat). Nor-β-lapachones arylamino substituted with potent activity were identified, revealing themselves as potential prototypes against tumor cell lines. Moreover, cells treated with these compounds showed DNA damage according to the standard comet assay, a finding that was, at least in part, due to increased intracellular levels of ROS. HL-60 cells were chosen to study the underlying molecular mechanisms of cytotoxicity. Drug-induced apoptosis in HL-60 cells was observed by flow cytometry analyses. Strains of Saccharomyces cerevisiae were used for a preliminary investigation into the mechanism of drug action on DNA topoisomerases. These results suggested that the cytotoxicity of these compounds apparently does not involve topoisomerase inhibition, but that treatment impairs DNA repair activity, thus triggering cell death. Considering their pro-oxidant properties, we investigated the ability of these compounds to induce apoptosis and chromosomal aberrations as micronuclei in Chinese hamster lung fibroblasts (V79 cells). Morphological apoptotic nuclei and micronuclei induction following drug treatment were observed, suggesting a correlation between DNA damage and apoptosis.