Anthracyclinones from <i>Micromonospora</i> sp.

Four new anthracyclinones, 4,6,11-trihydroxy-9-propyltetracene-5,12-dione (<b>1</b>), 1-methoxy-9-propyltetracene-6,11-dione (<b>2</b>), 7,8,9,10-tetrahydro-9-hydroxy-1-methoxy-9-propyltetracene-6,11-dione (<b>3</b>), and 10β-carbomethoxy-7,8,9,10-tetrahydro-4,6,7α,9α,11-pentahydroxy-9-propyltetracene-5,12-dione (<b>4</b>), were isolated from a strain of <i>Micromonospora</i> sp. associated with the tunicate <i>Eudistoma vannamei</i>. All structures were established by 1D and 2D NMR (COSY, HSQC, HMBC, NOESY) and HRESIMS experiments. Compounds <b>1</b> and <b>4</b> were cytotoxic against the HCT-8 human colon adenocarcinoma cell line, with IC₅₀ values of 12.7 and 6.2 μM, respectively, while compounds <b>2</b> and <b>3</b> were inactive

Cytotoxic compounds from the marine-derived fungus <i>Aspergillus</i> sp. recovered from the sediments of the Brazilian coast

<div><p>A fungal strain of <i>Aspergillus</i> sp. (BRF 030) was isolated from the sediments collected in the northeast coast of Brazil, and the cytotoxic activity of its secondary metabolites was investigated against HCT-116 tumour cell line. The cytotoxicity-guided fractionation of the extracts from this fungus cultured in potato-dextrose-sea water for 14 days at room temperature yielded the hetero-spirocyclic γ-lactams pseurotin A (<b>1</b>), pseurotin D (<b>2</b>) and pseurotin FD-838 (<b>7</b>), the alkaloids fumitremorgin C (<b>5</b>), 12,13-dihydroxy fumitremorgin C (<b>6</b>), methylsulochrin (<b>4</b>) and bis(dethio)bis(methylthio)gliotoxin (<b>3</b>). Among them, fumitremorgin C (<b>5</b>) and 12,13-dihydroxy fumitremorgin C (<b>6</b>) were the most active. The cytotoxic activities of the extracts from <i>Aspergillus</i> sp. grown from 7 to 28 days were investigated, and they were associated with the kinetic production of the compounds. The most active extracts (14 and 21 days) were those with the highest relative concentrations of the compounds fumitremorgin C (<b>5</b>) and 12,13-dihydroxy fumitremorgin C (<b>6</b>).</p></div

Cytotoxic Plakortides from the Brazilian Marine Sponge <i>Plakortis angulospiculatus</i>

Three new plakortides, 7,8-dihydroplakortide E (<b>1</b>), <b>2</b>, and <b>10</b>, along with known natural products <b>3</b>, <b>4</b>, spongosoritin A (<b>5</b>), <b>6</b>–<b>8</b>, and plakortide P (<b>9</b>), were isolated from Brazilian specimens of <i>Plakortis angulospiculatus</i>. Compounds <b>2</b>, <b>3</b>, <b>5</b>, and <b>7</b>–<b>9</b> displayed cytotoxic activities with IC₅₀ values ranging from 0.2 to 10 μM. Compounds that contained a dihydrofuran ring were generally less active and displayed time dependence in their activity. The activities of compounds <b>2</b> and <b>7</b>–<b>9</b>, carboxylic acids bearing a common six-membered endoperoxide, were higher overall than for compounds <b>3</b> and <b>5</b>. The modes underlying the cytotoxic actions of plakortides <b>2</b>, <b>3</b>, <b>5</b>, <b>7</b>, and <b>9</b> were further investigated using HCT-116 cells. While dihydrofurans <b>3</b> and <b>5</b> induce a G₀/G₁ arrest, six-membered peroxides <b>2</b>, <b>7</b>, and <b>9</b> delivered a G₂/M arrest and an accumulation of mitotic figures, indicating a distinctly different antimitotic response. Confocal analysis indicated that microtubules were not altered after treatment with <b>2</b>, <b>7</b>, or <b>9</b>, therein suggesting that the mitotic arrest may be unrelated to cytoskeletal targets. Overall, we find that two related classes of natural products obtained from the same extract offer cytostatic activity, yet they do so through discrete pathways