Anteaglonialides A–F and Palmarumycins CE₁–CE₃ from <i>Anteaglonium</i> sp. FL0768, a Fungal Endophyte of the Spikemoss <i>Selaginella arenicola</i>

Anteaglonialides A–F (<b>1</b>–<b>6</b>), bearing a spiro­[6-(tetrahydro-7-furanyl)­cyclohexane-1,2′-naphtho­[1,8-<i>de</i>]­[1,3]-dioxin]-10-one skeleton, three new spirobisnaphthalenes, palmarumycins CE₁–CE₃ (<b>7</b>–<b>9</b>), nine known palmarumycin analogues, palmarumycins CP₅ (<b>10</b>), CP_4a (<b>11</b>), CP₃ (<b>12</b>), CP₁₇ (<b>13</b>), CP₂ (<b>14</b>), and CP₁ (<b>15</b>), CJ-12,371 (<b>16</b>), 4-<i>O</i>-methyl CJ-12,371 (<b>17</b>), and CP₄ (<b>18</b>), together with a possible artifact, 4a(5)-anhydropalmarumycin CE₂ (<b>8a</b>), and four known metabolites, <i>O</i>-methylherbarin (<b>19</b>), herbarin (<b>20</b>), herbaridine B (<b>21</b>), and hyalopyrone (<b>22</b>), were encountered in a cytotoxic extract of a potato dextrose agar culture of <i>Anteaglonium</i> sp. FL0768, an endophytic fungus of the sand spikemoss, <i>Selaginella arenicola.</i> The planar structures and relative configurations of the new metabolites <b>1</b>–<b>9</b> were elucidated by analysis of extensive spectroscopic data, and the absolute configuration of <b>1</b> was determined by the modified Mosher’s ester method. Application of the modified Mosher’s ester method combined with the NOESY data resulted in revision of the absolute configuration previously proposed for <b>10</b>. Co-occurrence of <b>1</b>–<b>6</b> and <b>7</b>–<b>18</b> in this fungus led to the proposal that the anteagloniolides may be biogenetically derived from palmarumycins. Among the metabolites encountered, anteaglonialide F (<b>6</b>) and known palmarumycins CP₃ (<b>12</b>) and CP₁ (<b>15</b>) exhibited strong cytotoxic activity against the human Ewing’s sarcoma cell line CHP-100, with IC₅₀ values of 1.4, 0.5, and 1.6 μM, respectively

NEW SEMISYNTHETIC DERIVATIVES OF A BENZYLISOTHIOCYANATE ISOLATED FROM Moringa oleifera AND EVALUATION OF THEIR CYTOTOXIC ACTIVITY

<div><p>From the natural product 4-(4'-O-acetyl-α-L-rhamnosyloxy)benzylisothiocyanate (1), isolated from the flowers of Moringa oleifera Lam (Moringaceae), four new semisynthetic derivatives, N-[4-(4'-O-acetyl-α-L-rhamnosyloxy)benzyl]-2-(pyridinil-4-carbonil)hydrazine-1-carbothioamide (3), 4-(4'-O-acetyl-2',3'-dimesyloxy-α-L-rhamnosyloxy)benzylisothiocyanate (4), N-[(4'-O-acetyl-α-L-rhamnosyloxy)benzyl]hydrazinecarbothioamide (5), 4-[4'-O-acetyl-2',3'-O-bis(decanoiloxy)-α-L-rhamnosyloxy]benzylisothiocianate (6), and the known compound 4-(2',3',4'-O-triacetyl-α-L-rhamnosyloxy)benzylisothiocyanate (2), were obtained. All compounds were tested for their cytotoxicity against the tumor cell lines SF-295, HL-60, HCT-116 e PC-3. The natural product 1 and the semisynthetic derivatives 2 and 4 were the most active compounds (IC50 from16.0 to 3.7 µmol L-1) against all tumor cell lines.</p></div

Withaferin A and Withanolide D Analogues with Dual Heat-Shock-Inducing and Cytotoxic Activities: Semisynthesis and Biological Evaluation

Withanolides constitute a valuable class of bioactive natural products because some members of the class are known to exhibit cytotoxic activity and also induce a cytoprotective heat-shock response. In order to understand the relationship between their structures and these dual bioactivities of the withanolide scaffold, we obtained 25 analogues of withaferin A (WA) and withanolide D (WD) including 17 new compounds by semisynthesis involving chemical and microbial transformations. Hitherto unknown 16β-hydroxy analogues of WA and WD were prepared by their reaction with triphenylphosphine/iodine, providing unexpected 5β-hydroxy-6α-iodo analogues (iodohydrins) followed by microbial biotransformation with <i>Cunninghamella echinulata</i> and base-catalyzed cyclization of the resulting 16β-hydroxy iodohydrins. Evaluation of these 25 withanolide analogues for their cytotoxicity and heat-shock-inducing activity (HSA) confirmed the known structure–activity relationships for WA-type withanolides and revealed that WD analogues were less active in both assays compared to their corresponding WA analogues. The 5β,6β-epoxide moiety of withanolides contributed to their cytotoxicity but not HSA. Introduction of a 16β-OAc group to 4,27-di-<i>O</i>-acetyl-WA enhanced cytotoxicity and decreased HSA, whereas introduction of the same group to 4-<i>O</i>-acetyl-WD decreased both activities

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

Biologically Active Volatile Organic Compounds (VOCs) Produced by Rhizospheric Actinobacteria Strains Inhibit the Growth of the Phytopathogen Colletotrichum musae

The antifungal potential of volatile organic compounds (VOCs) produced by actinobacterial strains Streptomyces sp. (ACTB-77) and Amycolatopsis sp. (ACTB-290) from the rhizosphere of Caatinga plants against Colletotrichum musae was investigated. VOCs produced by these microorganisms (axenic and co-culture) were investigated using headspace-solid phase micro-extraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS). Although no exclusive VOC peaks were observed in the co-culture with ACTB-77, the same experiment involving ACTB-290 yielded five new peaks, including two identified alcohols, suggested as bioreductive products of the corresponding ketones by the fungus. Statistical analysis revealed that co-culture ACTB-77/C. musae has a closer similarity to the fungus than to the actinobacteria, while the co culture ACTB-290/C. musae showed closer similarity to the actinobacteria. These confirmed the more pronounced antifungal activity of the ACTB-290 strain, as observed in the fungus growth inhibition experiments. The antifungal activity of ACTB-290 was associated to its sulfur-containing metabolites, while linalool was suggested as responsible for the ACTB-77 activity.</div