Abstract The extensive marine biodiversity has proved to be a promising source of substances with biomedical potential. In this study, the cytotoxicity of the Brazilian octocoral Phyllogorgia dilatata (Gorgoniidae) was evaluated against two tumor cell lines and three bacterial strains. The methanol/dichloromethane crude extract presented no antibacterial activity up to the highest concentration tested (512 µg/mL), however it revealed a noteworthy antiproliferative effect against HCT-116 (80%) and MCF-7 (54%) cell lines at 50 μg/mL. Therefore, guided by the cytotoxic activity, a multistep chemical fractionation of the extract provided the subfraction 5 (PDPH2-5) with IC50 values of 3.18 and 17.80 μg/mL against HCT-116 and MCF-7, respectively. The LC-HRMS/MS analysis of PDPH2-5 showed ions of m/z 219.1742 and 219.1743, characterized as (E,E) and (Z,E) germacrone, after a LC-DAD-SPE/NMR analysis of the hexanic fraction and comparisons of NMR data with the literature. Previously reported assessments to the cytotoxic activity of the (E,E)-diastereoisomer disclosed higher IC50 values than that obtained for the PDPH2-5 fraction, suggesting, herein, a potentiated effect of the diastereoisomeric mixture. Such remark encourage further bioactivity studies with stereoisomer mixtures and reduce the urge for compound isolation.

A Streptomyces sp. (BRA-384) was selected among nine strains of bacteria isolated from the zoanthids Palythoa caribaeorum due to the high cytotoxic activity presented by its EtOAc extract (inhibitory concentration mean (IC50) of 2 ng mL-1) against colon cancer cell line. From the EtOAc extract of BRA-384 three new chemical entities (A6, A7 and A8) and one dextrorotatory chromomycin (A5), a promising class of anticancer compounds, were identified. The cytotoxicity of chromomycins A5 to A8 was tested against five tumor cell lines (HCT 116 (human colon adenocarcinoma), MCF-7 (human breast carcinoma), PC-3M (human metastatic prostate cancer), 501-mel (human metastatic melanoma) and MM200 (metastatic melanoma)). All chromomycins were highly potent showing IC50 values from 0.2 to 133 nM. Chromomycin A5 was consistently the most potent over all tested cells (IC50 values from 0.2 in MM200 to 7.9 nM in PC-3M), inclusive when compared to the standard chemotherapeutic agent doxorubicin, that presented IC50 values ranging from 147 to 568 nM against MM200 and MCF-7, respectively.

Seriniquinone is a natural quinone isolated from a rare marine bacterium of the genus Serinicoccus. This secondary metabolite has been shown to have anticancer properties, which has raised attention of the scientific community. In this short report, we present the first investigation of the gas-phase chemistry fragmentation reactions of seriniquinone in electrospray ionization tandem mass spectrometry (ESI-MS/MS), to be further applied in pharmacokinetics and metabolism studies. All the proposals herein were supported by computational chemistry.

ABSTRACT Natural steroids and triterpenes such as b-sitosterol, stigmasterol, lupeol, ursolic and betulinic acids were transformed into its hexanoic and oleic esters, to evaluate the influence of chemical modification towards the cytotoxic activities against tumor cells. The derivatives were evaluated against five tumor cell lines [OVCAR-8 (ovarian carcinoma); SF-295 (glioblastoma); HCT-116 (colon adenocarcinoma); HL-60 (leukemia); and PC-3 (prostate carcinoma)] and the results showed only betulinic acid hexyl ester exhibits cytotoxic potential activity.

A series of 2-hydroxy-3-arylnaphthalene-1,4-diones (3-aryllawsones) were synthesized by Suzuki-Miyaura cross coupling reaction of 3-iodolawsone with arylboronic acids/esters. The hydroxylated resulting products were transformed into their corresponding N,N-diethyl carbamates. The antineoplastic and antileishmanial activities of the compounds were evaluated and compared with lapachol and its carbamate, providing promising results.

Two unreported ergostane-type sterols 24(R)-7α-hydroperoxy-ergost-5-en-3β-ol and 6β-carboxyl-24(R)-(8→6)-abeo-ergostan-3β,5β-diol, along with seven known ones were isolated from the hexane and alcohol extracts from the zoanthids Palythoa caribaeorum and Palythoa variabilis. The structures of the new compounds were determined using spectroscopic techniques, including 1D and 2D nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectrometry (HRESIMS), and comparison with data previously published. 6β-Carboxyl-24(R)-(8→6)-abeo-ergostan-3β,5β-diol showed moderate cytotoxicity against colon cancer cells (HCT-116) as previously described for others abeo-sterol derivatives.

Four new epimeric spirostanol and furostanol-type steroidal saponins, (25R,S)-5α-spirostan-2α,3β-diol 3-O-β-D-glucopyranosyl-(1→4)-β-D-galactopyranosyl-(1→4)-β-D-galactopyranoside, (25R,S)-5α-spirostan-2α,3β-diol 3-O-β-D-glucopyranosyl-(1→2)-α-L-rhamnopyranosyl-(1→4)-β-D-galactopyranoside, 26-O-β-D-glucopyranosyl-(25R,S)-5α-furost-20-ene,2α,3β-diol 3-O-β-D-galactopyranoside and 26-O-β-D-glucopyranosyl-(25R,S)-5α-furost-20-ene,2α,3β-diol 3-O-β-D-galactopyranosyl-(1→4)-β-D-galactopyranoside, in addition to the known (25R,S)-5α-spirostan-2α,3β-diol 3-O-β-D-galactopyranoside, were isolated from Cestrum laevigatum. Compounds were submitted to cytotoxic activity assays using colorectal adenocarcinoma (HCT-116), human promyelocytic leukemia (HL-60), ovarian carcinoma (OVCAR-8), glioma (SF-295) human cancer cell lines, and the antimicrobial activity was evaluated against Candida parapsilosis, C. albicans, C. krusei, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis.

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 Methanolic extracts of the Brazilian endemic ascidian Eudistoma vannamei have been extensively studied for their cytotoxic activity against several human cancer cell lines. Previous work reported the occurrence of purine derivatives and staurosporine alkaloids as the major nitrogen-containing compounds. In this study, we report the occurrence of three pyrimidine alkaloids in addition to cholesterol, sitosterol and stigmasterol.

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.

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.

<p>An asymmetrical dimer of kaurane diterpene and monoterpene and four novel diterpenes were isolated from the roots of <italic>Croton limae</italic>, along with kaempferol-3-<italic>O</italic>-glucoside, ombuin- 3-O-rutinoside and acetyl aleuritolic acid. The cytotoxic activity of the kaurane diterpene was evaluated against colorectal adenocarcinoma (HCT-116), ovarian carcinoma (OVCAR-8) and glioma (SF-295) cell lines, exhibiting IC₅₀ values of 7.14, 8.19 and > 10 µg mL⁻¹, respectively.</p>

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.

Três novos complexos de platina(IV), cis,cis,trans-[Pt(HL1-3)Cl2(OH)2] 1b-3b (HL = 2-hidroxi3-[(R¹-amino)(piridin-2-il)metil]-1,4-naftoquinona, R¹ = n-butil, HL1; n-heptil, HL2 and n-decil, HL3) foram obtidos através da oxidação dos respectivos precursores cis-[Pt(HL1-3)Cl2] 1a-3a. Estudos de voltametria cíclica de 1b-3b em MeCN mostraram o processo redox quase reversível do íon naftoquinonato (NQO-, i.e. , L-) e o processo irreversível atribuído à redução do par Pt4+/Pt2+, em potenciais aproximadamente 400 mV menos negativos que no precursor da cisplatina cis,cis,trans-[Pt(NH3)2Cl2(OH)2]. Propõe-se que este processo Pt4+/Pt2+ seja favorecido, em 1b-3b, por uma interação de hidrogênio entre o grupo 2-hidroxil da naftoquinona e um ligante hidroxil axial. Estudos de citotoxicidade contra quatro linhagens de células tumorais humanas mostraram que, em geral, os derivados de platina(IV) e platina(II) exibem o mesmo perfil citotóxico, além de serem mais ativos que a cisplatina. Valores de CI50 in vitro mais baixos foram observados para 2b-3b, cujos ligantes possuem os maiores grupos R¹ (HL2-HL3), sendo, portanto, mais lipofílicos. Além disto, os valores semelhantes de CI50 dos complexos análogos de platina(II) e platina(IV) devem-se à rápida redução de 1b-3b in vitro para gerar 1a-3a.

Three novel platinum(IV) complexes cis,cis,trans-[Pt(HL1-3)Cl2(OH)2] 1b-3b (HL = 2-hydroxy-3-[(R¹-amino)(pyridin-2-yl)methyl]-1,4-naphthoquinone, R¹ = n-butyl, HL1; n-heptyl, HL2 and n-decyl, HL3) have been obtained from the oxidation of the respective precursors cis-[Pt(HL1-3)Cl2] 1a-3a. Cyclic voltammetry studies of 1b-3b in MeCN showed the quasi-reversible naphthoquinonate (NQO-, i.e. , L-) redox process and irreversible process attributed to the reduction of the Pt4+/Pt2+ pair, at potentials about 400 mV less negative than for the cisplatin precursor cis,cis,trans-[Pt(NH3)2Cl2(OH)2]. Hydrogen bond interaction between the naphthoquinone 2-hydroxyl group and an axially coordinated hydroxide ligand in 1b-3b has been proposed to favor the Pt4+/Pt2+ reduction. The cytotoxicity studies against four human cancer cell lines have shown that in general the platinum(IV) and platinum(II)derivatives exhibit the same cytotoxic profile and are all more active than cisplatin. The lowest in vitro IC50 values have been observed for 2b-3b, which bear ligands with the largest R¹ groups (HL2-HL3) being the most lipophilic. Furthermore similar IC50 values for platinum(II) and platinum(IV) complexes of the same ligands have been associated with rapid in vitro reduction of the latter complexes to afford 1a-3a.

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.