The actinomycete strain BRA 177 was recovered from sediment samples collected at the St. Peter and St. Paul Archipelago, Brazil. This work accessed the ability of this strain, identified as Actinomadura sp., to produce bioactive metabolites by exploring the genome and characterizing chemistry and cytotoxicity of isolated compounds. From the crude ethyl acetate extract, the pigments nonylprodigiosin, cyclononylprodigiosin and methylcyclooctilprodigiosin were isolated and displayed cytotoxicity against human tumor and non-tumor cell lines. Sequencing, assembling and prospection of BRA 177 draft genome led to identification of two contigs encoding enzymes with high homology to those from prodiginine biosynthetic gene clusters (BGC) in actinomycetes. Further, Actinomadura sp. BGC presented unique putatives RedJ thioesterase and RedL-like type I PKS, involved on selection of prodiginine biosynthetic fatty acyl precursor, and RedG-like Rieske oxygenase, key for cyclization of the prodiginines, suggesting that cyclononilprodigiosin and methylcyclooctylprodigiosin could actually be considered chemical signatures of Actinomadura spp.

Abstract Marine environment is one of the most important sources regarding natural products research. Besides, marine microorganisms have been denominated as a talented natural source for discovery of new leads. Although the association of macroalgae and fungi has been described regarding ecological issues, there is a lack of studies about marine seaweed endophytic fungi. In this context, the goal of this study was to evaluate cytotoxic, antifungal and antibacterial activities of endophytic fungi isolated from the Brazilian marine seaweed Bostrychia tenella (J.V. Lamouroux) J. Agardh (Ceramiales, Rhodophyta). Forty-five endophytic microorganism strains were isolated from B. tenella. Crude extracts and organic fractions of ten selected strains were obtained after growth in rice medium. Samples were evaluated for cytotoxicity, antifungal and antibacterial assays. Penicillium strains showed positive results in a diversity of assays, and other five strains were active in at least one test. In addition, cytochalasin D was isolated from Xylaria sp. This alga is composed of a microbiological potential, since its endophytic strains exhibited remarkable biological properties. Moreover, cytochalasin D isolation has confirmed chemical potential of marine endophytic strains. This is the first study in which cultured fungi isolates from the Brazilian macroalga B. tenella were evaluated concerning biological properties. Results corroborated that this species could be a pharmaceutical source from marine environment. Furthermore, Acremonium implicatum is being firstly described as marine endophyte and Xylaria sp., Trichoderma atroviride and Nigrospora oryzae as marine seaweed endophytes. Thus, this work reports the first study relating detailed isolation, cultivation and biological evaluation (cytotoxic, antifungal and antibacterial) of endophytes Penicillium decaturense and P. waksmanii from the Brazilian marine red alga B. tenella. We are also reporting the isolation of cytochalasin D, a known antitumor and antibiotic compound, from Xylaria sp. strain. Despite widespread prevalence in terrestrial and marine habitats, this present work describes the first occurrence of cytochalasin D as a metabolite from marine seaweed endophyte.

Abstract Four bisabolanes 1–4, including perezone (1) and triacetyl perezone (2), were isolated through a bioassay-guided fractionation of the extract obtained from the Caribbean gorgonian coral Pseudopterogorgia rigida collected during an expedition cruise to the Bahamas. All isolated compounds showed to be cytotoxic toward panel of four human tumor cell lines, as quantified by the MTT assay after 72 h incubation. Perezone (1), the most active one, was further analyzed, showing to be cytotoxic, but not selective, in a 12-cell line panel comprising tumor and non-tumor, as well as human and murine cells. Additionally, 1 was assayed for cytotoxicity against HL-60 leukemic cells. Pre-treatment with an acute free radical scavenger (L-NAC) before exposure of cells to perezone virtually eliminated the generation of intracellular ROS and lessened its severe cytotoxicity. The protective effect delivered by L-NAC evidences that the mechanism of perezone-induced cytotoxicity is partially associated to production of ROS and a consequent induction of oxidative stress.

Two new alkaloids containing Nb-methyl-triptamine units linked to bis-quinoline moieties, N-8”-formyl-calycosidine and N-8”-methyl-N-1’-demethyl-iso-calycosidine, were isolated from the aerial part of Margaritopsis carrascoana, along with known calycosidine and hodgkinsine. The cytotoxicity of the isolated alkaloids has been evaluated against cancer cell lines. The first two compounds showed only weak activity against HL-60 cell line, while hodgkinsine was the most active compound against HCT-116, OVCAR-8, HL-60 and SF-295 cancer cell lines. The structures of the isolated compounds were established by spectroscopic and molecular mechanical methods.

Previous studies demonstrated that the crude extract of the ascidian Eudistoma vannamei, endemic from northeasttern Brazil, strongly hinders growth of tumor cells in vitro by inducing apoptosis due to tryptophan derivatives, which are commonly found in bacteria. This study presents a bioactivity-guided screening among actinomycetes, associated with E. vannamei, aiming at recognizing active principles with biological relevance. Twenty strains of actinomycetes, designated as EVA 0101 through 0120, were isolated from colonies of E. vannamei among which 11 were selected for cytotoxicity evaluation. The extracts from EVA 0102, 0103, 0106, 0109 and 0113 were the most active, and were further studied for IC50 determination and chemical analysis by ¹H NMR. IC50 values obtained ranged from 3.62 µg mL-1 (for EVA 0109 in leukemia cells) to 84.65 µg/mL (for EVA 0106 in melanoma cells). All active extracts exhibited the same TLC and spectroscopic profiles, suggesting the presence of quinones and other related secondary metabolites. Furthermore, these strains were identified and compared based on their respective 16S rRNA sequences. The results herein identified the five strains as Micromonospora spp. while phylogenetic analysis suggests that they are possibly two different Micromonospora species producing the cytotoxic compounds.

Estudios previos demostraron que el extracto crudo de la ascidia Eudistoma vannamei, endémica de la costa noreste de Brasil, obstaculiza fuertemente el crecimiento de células tumorales in vitro por inducir apoptosis. El análisis químico del extracto sugirió la presencia de derivados de triptófano, comúnmente encontrados en bacterias. El estudio presenta un screening de citotoxicidad en actinomicetos asociados con E. vannamei, para reconocer principios activos biológicamente relevantes. Veinte cepas de actinomicetos, designados como EVA 0101 hasta 0120, fueron aisladas de colonias de E. vannamei y 11 fueron seleccionadas para la evaluación de citotoxicidad. Los extractos de EVA 0102, 0103, 0106, 0109 y 0113 resultaron las más activas y fueron estudiadas para determinación de la CL50 y perfiles de CCF y ¹H RMN. Las CL50 obtenidas oscilaron entre 3,62 (EVA 0109 en las células de leucemia) y 84,65 µg mL-1 (EVA 0106 en las células de melanoma). Los extractos activos presentan el mismo perfil de CCF y espectroscópico, lo que sugiere la presencia de quinonas y metabolitos secundarios relacionados. Además, las cinco cepas fueron identificadas y comparadas sobre la base de sus secuencias de 16S ARNr. Las que se identificaron como Micromonospora spp. y el análisis filogenético sugiere que sean por lo menos dos especies de Micromonospora las que producen los compuestos citotóxicos.