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1.
Mar Drugs ; 22(7)2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39057426

RESUMO

Ten new decalin polyketides, zosteropenilline M (1), 11-epi-8-hydroxyzosteropenilline M (2), zosteropenilline N (3), 8-hydroxyzosteropenilline G (4), zosteropenilline O (5), zosteropenilline P (6), zosteropenilline Q (7), 13-dehydroxypallidopenilline A (8), zosteropenilline R (9) and zosteropenilline S (10), together with known zosteropenillines G (11) and J (12), pallidopenilline A (13) and 1-acetylpallidopenilline A (14), were isolated from the ethyl acetate extract of the fungus Penicillium yezoense KMM 4679 associated with the seagrass Zostera marina. The structures of isolated compounds were established based on spectroscopic methods. The absolute configurations of zosteropenilline Q (7) and zosteropenilline S (10) were determined using a combination of the modified Mosher's method and ROESY data. The absolute configurations of zosteropenilline M (1) and zosteropenilline N (3) were determined using time-dependent density functional theory (TD-DFT) calculations of the ECD spectra. A biogenetic pathway for compounds 1-14 is proposed. The antimicrobial, cytotoxic and cytoprotective activities of the isolated compounds were also studied. The significant cytoprotective effects of the new zosteropenilline M and zosteropenillines O and R were found in a cobalt chloride (II) mimic in in vitro hypoxia in HEK-293 cells. 1-Acetylpallidopenilline A (14) exhibited high inhibition of human breast cancer MCF-7 cell colony formation with IC50 of 0.66 µM and its anticancer effect was reduced when MCF-7 cells were pretreated with 4-hydroxitamoxifen. Thus, we propose 1-acetylpallidopenilline A as a new xenoestrogen with significant activity against breast cancer.


Assuntos
Penicillium , Zosteraceae , Penicillium/química , Humanos , Linhagem Celular Tumoral , Policetídeos/farmacologia , Policetídeos/química , Policetídeos/isolamento & purificação , Células MCF-7 , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Organismos Aquáticos
2.
Nat Prod Bioprospect ; 14(1): 32, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38769256

RESUMO

Four extracts of the marine-derived fungus Penicillium velutinum J.F.H. Beyma were obtained via metal ions stress conditions based on the OSMAC (One Strain Many Compounds) strategy. Using a combination of modern approaches such as LC/UV, LC/MS and bioactivity data analysis, as well as in silico calculations, influence metal stress factors to change metabolite profiles Penicillium velutinum were analyzed. From the ethyl acetate extract of the P. velutinum were isolated two new piperazine derivatives helvamides B (1) and C (2) together with known saroclazin A (3) (4S,5R,7S)-4,11-dihydroxy-guaia-1(2),9(10)-dien (4). Their structures were established based on spectroscopic methods. The absolute configuration of helvamide B (1) as 2R,5R was determined by a combination of the X-ray analysis and by time-dependent density functional theory (TD-DFT) calculations of electronic circular dichroism (ECD) spectra. The cytotoxic activity of the isolated compounds against human prostate cancer PC-3 and human embryonic kidney HEK-293 cells and growth inhibition activity against yeast-like fungi Candida albicans were assayed.

3.
Biomolecules ; 13(5)2023 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-37238611

RESUMO

The KMM 4639 strain was identified as Amphichorda sp. based on two molecular genetic markers: ITS and ß-tubulin regions. Chemical investigation of co-culture marine-derived fungi Amphichorda sp. KMM 4639 and Aspergillus carneus KMM 4638 led to the identification of five new quinazolinone alkaloids felicarnezolines A-E (1-5), a new highly oxygenated chromene derivative oxirapentyn M (6) and five previously reported related compounds. Their structures were established using spectroscopic methods and by comparison with related known compounds. The isolated compounds showed low cytotoxicity against human prostate and breast cancer cells but felicarnezoline B (2) protected rat cardiomyocytes H9c2 and human neuroblastoma SH-SY5Y cells against CoCl2-induced damage.


Assuntos
Hypocreales , Neuroblastoma , Humanos , Ratos , Animais , Técnicas de Cocultura , Estrutura Molecular , Fungos/química
4.
Mar Drugs ; 21(3)2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36976227

RESUMO

Five new ß-resorcylic acid derivatives, 14-hydroxyasperentin B (1), ß-resoantarctines A-C (3, 5, 6) and 8-dehydro-ß-resoantarctine A (4), together with known 14-hydroxyasperentin (5'-hydroxyasperentin) (2), were isolated from the ethyl acetate extract of the fungus Penicillium antarcticum KMM 4685 associated with the brown alga Sargassum miyabei. The structures of the compounds were elucidated by spectroscopic analyses and modified Mosher's method, and the biogenetic pathways for compounds 3-6 were proposed. For the very first time, the relative configuration of the C-14 center of a known compound 2 was assigned via analyses of magnitudes of the vicinal coupling constants. The new metabolites 3-6 were biogenically related to resorcylic acid lactones (RALs); however, they did not possess lactonized macrolide elements in their structures. Compounds 3, 4 and 5 exhibited moderate cytotoxic activity in LNCaP, DU145 and 22Rv1 human prostate cancer cells. Moreover, these metabolites could inhibit the activity of p-glycoprotein at their noncytotoxic concentrations and consequently synergize with docetaxel in p-glycoprotein-overexpressing drug-resistant cancer cells.


Assuntos
Penicillium , Humanos , Estrutura Molecular , Penicillium/química , Fungos/química
5.
Mar Drugs ; 21(1)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36662227

RESUMO

Marine fungi serve as a valuable source for new bioactive molecules bearing various biological activities. In this study, we report on the isolation of a new indole diketopiperazine alkaloid deoxy-14,15-dehydroisoaustamide (1) from the marine-derived fungus Penicillium dimorphosporum KMM 4689 associated with a soft coral. The structure of this metabolite, including its absolute configuration, was determined by HR-MS, 1D and 2D NMR as well as CD data. Compound 1 is a very first deoxyisoaustamide alkaloid possessing two double bonds in the proline ring. The isolated compound was noncytotoxic to a panel of human normal and cancer cell lines up to 100 µM. At the same time, compound 1 resensitized prostate cancer 22Rv1 cells to androgen receptor (AR) blocker enzalutamide. The mechanism of this phenomenon was identified as specific drug-induced degradation of androgen receptor transcription variant V7 (AR-V7), which also resulted in general suppression of AR signaling. Our data suggest that the isolated alkaloid is a promising candidate for combinational therapy of castration resistant prostate cancer, including drug-resistant subtypes.


Assuntos
Antineoplásicos , Neoplasias de Próstata Resistentes à Castração , Humanos , Masculino , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Nitrilas/farmacologia , Nitrilas/uso terapêutico , Feniltioidantoína/farmacologia , Feniltioidantoína/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Receptores Androgênicos/metabolismo
6.
Mar Drugs ; 20(9)2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36135773

RESUMO

Chemical investigation of a coculture of the marine-derived fungi Beauveria felina KMM 4639 and Aspergillus carneus KMM 4638 led to the identification of three new drimane-type sesquiterpenes, asperflavinoids B, D and E (2, 4, 5), and nine previously reported related compounds. The structures of these compounds were established using spectroscopic methods and by comparison with known analogues. We also investigated the cytotoxic activity of the isolated compounds against several cancer and normal cell lines. Asperflavinoid C (3) and ustusolate E (9) exerted a significant effect on human breast cancer MCF-7 cell viability, with IC50 values of 10 µM, and induced in caspase-dependent apoptosis and arrest of the MCF-7 cell cycle in the G2/M phase in these cells.


Assuntos
Antineoplásicos , Beauveria , Sesquiterpenos , Antineoplásicos/química , Aspergillus , Beauveria/química , Linhagem Celular Tumoral , Técnicas de Cocultura , Humanos , Estrutura Molecular , Sesquiterpenos Policíclicos , Sesquiterpenos/química
7.
Mar Drugs ; 19(1)2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33445521

RESUMO

Seven new deoxyisoaustamide derivatives (1-7) together with known compounds (8-10) were isolated from the coral-derived fungus Penicillium dimorphosporum KMM 4689. Their structures were established using spectroscopic methods, X-ray diffraction analysis and by comparison with related known compounds. The absolute configurations of some alkaloids were determined based on CD and NOESY data as well as biogenetic considerations. The cytotoxic and neuroprotective activities of some of the isolated compounds were examined and structure-activity relationships were pointed out. New deoxyisoaustamides 4-6 at concentration of 1 µM revealed a statistical increase of PQ(paraquat)-treated Neuro-2a cell viability by 30-39%.


Assuntos
Antozoários , Antineoplásicos/isolamento & purificação , Indóis/isolamento & purificação , Penicillium/isolamento & purificação , Animais , Antozoários/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Cristalografia por Raios X/métodos , Humanos , Indóis/química , Indóis/farmacologia , Penicillium/química
8.
Nat Prod Res ; 34(8): 1118-1123, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30663353

RESUMO

Four new diketopiperazine alkaloids, citriperazines A-D were isolated from algae-derived Penicillium sp. KMM 4672. The structures of compounds 1-4 were determined using spectroscopic methods. The absolute configurations of compounds 1 and 4 were established by comparison of calculated and experimental ECD spectra. The cytotoxicity of compounds 1-4 against several human prostate cell lines was evaluated.


Assuntos
Dicetopiperazinas/isolamento & purificação , Penicillium/química , Alcaloides/química , Alcaloides/isolamento & purificação , Linhagem Celular Tumoral , Citotoxinas/química , Citotoxinas/isolamento & purificação , Citotoxinas/farmacologia , Dicetopiperazinas/química , Humanos , Conformação Molecular , Estrutura Molecular , Análise Espectral
9.
Mar Drugs ; 17(11)2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31752168

RESUMO

Six new carotane sesquiterpenoids piltunines A-F (1-6) together with known compounds (7-9) were isolated from the marine-derived fungus Penicillium piltunense KMM 4668. Their structures were established using spectroscopic methods. The absolute configurations of 1-7 were determined based on circular dichroism (CD) and nuclear Overhauser spectroscopy (NOESY) data as well as biogenetic considerations. The cytotoxic activity of some of the isolated compounds and their effects on regulation of reactive oxygen species (ROS) and nitric oxide (NO) production in lipopolysaccharide-stimulated macrophages were examined.


Assuntos
Antineoplásicos/farmacologia , Macrófagos/efeitos dos fármacos , Penicillium/química , Sesquiterpenos/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Células Cultivadas , Dicroísmo Circular , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação
10.
Mar Drugs ; 17(11)2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31671910

RESUMO

Ten new diterpene glycosides virescenosides Z9-Z18 (1-10) together with three known analogues (11-13) and aglycon of virescenoside A (14) were isolated from the marine-derived fungus Acremonium striatisporum KMM 4401. These compounds were obtained by cultivating fungus on wort agar medium with the addition of potassium bromide. Structures of the isolated metabolites were established based on spectroscopic methods. The effects of some isolated glycosides and aglycons 15-18 on urease activity and regulation of Reactive Oxygen Species (ROS) and Nitric Oxide (NO) production in macrophages stimulated with lipopolysaccharide (LPC) were evaluated.


Assuntos
Acremonium/química , Diterpenos/química , Glicosídeos/química , Glicosídeos/farmacologia , Macrófagos/efeitos dos fármacos , Animais , Diterpenos/isolamento & purificação , Fungos , Glicosídeos/isolamento & purificação , Holothuria/microbiologia , Lipopolissacarídeos , Camundongos , Estrutura Molecular , Óxido Nítrico , Espécies Reativas de Oxigênio , Urease/efeitos dos fármacos
11.
Mar Drugs ; 17(9)2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31450717

RESUMO

A simple approach toward the synthesis of the marine sponge derived pigment fascaplysin was used to obtain the marine alkaloids 3-bromofascaplysin and 3,10-dibromofascaplysin. These compounds were used for first syntheses of the alkaloids 14-bromoreticulatate and 14-bromoreticulatine. Preliminary bioassays showed that 14-bromoreticulatine has a selective antibiotic (to Pseudomonas aeruginosa) activity and reveals cytotoxicity toward human melanoma, colon, and prostate cancer cells. 3,10-Dibromofascaplysin was able to target metabolic activity of the prostate cancer cells, without disrupting cell membrane's integrity and had a wide therapeutic window amongst the fascaplysin alkaloids.


Assuntos
Alcaloides/farmacologia , Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Indóis/farmacologia , Poríferos/química , Alcaloides/síntese química , Animais , Antibacterianos/síntese química , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Técnicas de Química Sintética/métodos , Ensaios de Seleção de Medicamentos Antitumorais , Halogenação , Humanos , Indóis/síntese química , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos
13.
J Nat Prod ; 79(12): 3031-3038, 2016 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-28006908

RESUMO

Eleven new polyketides, pallidopenillines 1-11, were isolated from the alga-derived fungus Penicillium thomii. The structures of these compounds were established based on spectroscopic methods. The absolute configuration of pallidopenilline A (1) as 4R, 5S, 8S, 9R, 10R, 13R was established using a combination of the modified Mosher's method, X-ray analysis, and NOESY data. The absolute configurations of 2-5 were determined by time-dependent density functional theory calculations of the ECD spectra and ECD and NOESY data. It was shown that 1-acetylpallidopenilline A (2) and pallidopenilline G (10) inhibit the growth of colonies of 22Rv1 cells by 40% at 2 and 1 µM, respectively.


Assuntos
Antineoplásicos/isolamento & purificação , Penicillium/química , Policetídeos/isolamento & purificação , Antineoplásicos/química , Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Células HCT116 , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Policetídeos/química , Policetídeos/farmacologia , Sargassum/microbiologia
14.
Mar Drugs ; 14(7)2016 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-27355960

RESUMO

Three new epidithiodiketopiperazines pretrichodermamides D-F (1-3), together with the known N-methylpretrichodermamide B (4) and pretrichodermamide С (5), were isolated from the lipophilic extract of the marine algae-derived fungus Penicillium sp. KMM 4672. The structures of compounds 1-5 were determined based on spectroscopic methods. The absolute configuration of pretrichodermamide D (1) was established by a combination of modified Mosher's method, NOESY data, and biogenetic considerations. N-Methylpretrichodermamide B (5) showed strong cytotoxicity against 22Rv1 human prostate cancer cells resistant to androgen receptor targeted therapies.


Assuntos
Produtos Biológicos/química , Diterpenos/química , Fungos/química , Penicillium/química , Piperazinas/química , Produtos Biológicos/farmacologia , Linhagem Celular Tumoral , Diterpenos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Biologia Marinha/métodos , Estrutura Molecular , Piperazinas/farmacologia
15.
J Nat Prod ; 77(6): 1321-8, 2014 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-24911656

RESUMO

Six new highly oxygenated chromene derivatives, oxirapentyns F-K (2-7), one new polyketide (8), one new benzofurane (9), and two known cyclodepsipeptides, isoisariin B and isaridin E, were isolated from the lipophilic extract of the marine-derived fungus Isaria felina KMM 4639. The structures of compounds 2-9 were determined using spectroscopic methods. The relative configurations of compounds 2-7 were established through a combination of NOE data and spin coupling constants, and these results were confirmed by X-ray crystallographic analysis of 4. The absolute structures of all oxirapentyns were assumed based on their biogenetic relationship and confirmed using the modified Mosher's method on 2 and 7. Isariketide (8) showed moderate cytotoxicity toward HL-60 cells.


Assuntos
Alcinos/isolamento & purificação , Antineoplásicos/isolamento & purificação , Benzopiranos/isolamento & purificação , Depsipeptídeos/isolamento & purificação , Sedimentos Geológicos/química , Hypocreales/química , Alcinos/química , Alcinos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Benzopiranos/química , Benzopiranos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Depsipeptídeos/química , Ensaios de Seleção de Medicamentos Antitumorais , Células HL-60 , Humanos , Biologia Marinha , Testes de Sensibilidade Microbiana , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Oceanos e Mares
16.
J Nat Prod ; 70(6): 906-9, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17555349

RESUMO

Three new indole alkaloids, shearinines D, E, and F (1-3), together with the known shearinine A (4) were isolated from the marine-derived strain of the fungus Penicillium janthinellum Biourge. The chemical structures of 1-4 were established by 2D NMR and HREIMS data. Shearinines A, D, and E induce apoptosis in human leukemia HL-60 cells, and shearinine E also inhibits EGF-induced malignant transformation of JB6 P+ Cl 41 cells in a soft agar.


Assuntos
Anticarcinógenos/isolamento & purificação , Antineoplásicos/isolamento & purificação , Alcaloides Indólicos/isolamento & purificação , Penicillium/química , Anticarcinógenos/química , Anticarcinógenos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacologia , Biologia Marinha , Estrutura Molecular
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