RESUMO
One novel rearranged pimarane diterpenoid, pestanoid A (1), and two reported molecules, nodulisporenones A (2) and B (3), were discovered from Pestalotiopsis sp. NBUF145 fungus associated with a 62 m deep mesophotic ("twilight") zone Chalinidae sponge. The structures of 1-3 were identified by spectrometry, spectroscopy, quantum-chemical calculations, and X-ray crystallography. Compounds 1 and 2 inhibited bone marrow monocyte osteoclastogenesis in vitro with the IC50 values 4.2 ± 0.2 µM and 3.0 ± 0.4 µM, respectively, without observed cytotoxicity. Both 1 and 2 suppressed the receptor activator of NF-kB ligand-induced MAPK and NF-κB signaling by inhibiting the phosphorylation of ERK1/2-JNK1/2-p38 MAPKs and NF-κB nuclear translocation.
Assuntos
Osteoclastos , Osteogênese , NF-kappa B , Pestalotiopsis , Macrófagos , Abietanos , Ligante RANKRESUMO
Chemical investigation of Irpex sp. NBUF088, associated with an Ircinia sp. sponge located at an 84 m deep mesophotic zone, led to the discovery of two new heptaketides, named irpetones A (1) and B (2). Their structures were identified by analysis of spectroscopic data and quantum-chemical calculations. Compound 1 exhibited inhibition against the receptor activator of NF-κB ligand-induced osteoclastogenesis in bone marrow monocytes with an IC50 of 6.3 ± 0.2 µM, causing no notable cytotoxicity. It was also determined that 1 inhibited the phosphorylation of ERK1/2-JNK1/2-p38 MAPKs and the nuclear translocation of NF-κB, consequently suppressing the activation of MAPK and NF-κB signaling pathways induced by the NF-κB ligand.
Assuntos
Osteoclastos , Poríferos , Animais , Poríferos/microbiologia , Estrutura Molecular , Osteoclastos/efeitos dos fármacos , NF-kappa B/metabolismo , Camundongos , Osteogênese/efeitos dos fármacosRESUMO
Scientific conferences and meetings are valuable opportunities for researchers to network, communicate, and develop knowledge. For early career scientists, conferences can also be intimidating, confusing, and overwhelming, especially without having adequate preparation or experience. In this Perspective, we provide advice based on previous experiences navigating scientific meetings and conferences. These guidelines outline parts of the hidden curriculum around preparing for and attending meetings, navigating conference sessions, networking with other scientists, and participating in social activities while upholding a recommended code of conduct.
Assuntos
Congressos como Assunto , Currículo , HumanosRESUMO
Kavaratamide A (1), a new linear lipodepsipeptide possessing an unusual isopropyl-O-methylpyrrolinone moiety, was discovered from the tropical marine filamentous cyanobacterium Moorena bouillonii collected from Kavaratti, India. A comparative chemogeographic analysis of M. bouillonii collected from six different geographical regions led to the prioritized isolation of this metabolite from India as distinctive among our data sets. AI-based structure annotation tools, including SMART 2.1 and DeepSAT, accelerated the structure elucidation by providing useful structural clues, and the full planar structure was elucidated based on comprehensive HRMS, MS/MS fragmentation, and NMR data interpretation. Subsequently, the absolute configuration of 1 was determined using advanced Marfey's analysis, modified Mosher's ester derivatization, and chiral-phase HPLC. The structures of kavaratamides B (2) and C (3) are proposed based on a detailed analysis of their MS/MS fragmentations. The biological activity of kavaratamide A was also investigated and found to show moderate cytotoxicity to the D283-medullablastoma cell line.
Assuntos
Cianobactérias , Depsipeptídeos , Cianobactérias/química , Depsipeptídeos/química , Depsipeptídeos/farmacologia , Depsipeptídeos/isolamento & purificação , Estrutura Molecular , Índia , Ressonância Magnética Nuclear Biomolecular , Biologia Marinha , Humanos , Ensaios de Seleção de Medicamentos Antitumorais , Cromatografia Líquida de Alta PressãoRESUMO
The tropical marine cyanobacterium Moorena producens JHB is a prolific source of secondary metabolites with potential biomedical utility. Previous studies on this strain led to the discovery of several novel compounds such as hectochlorins and jamaicamides. However, bioinformatic analyses of its genome indicate the presence of numerous cryptic biosynthetic gene clusters that have yet to be characterized. To potentially stimulate the production of novel compounds from this strain, it was cocultured with Candida albicans. From this experiment, we observed the increased production of a new compound that we characterize here as hectoramide B. Bioinformatic analysis of the M. producens JHB genome enabled the identification of a putative biosynthetic gene cluster responsible for hectoramide B biosynthesis. This work demonstrates that coculture competition experiments can be a valuable method to facilitate the discovery of novel natural products from cyanobacteria.
Assuntos
Cianobactérias , Depsipeptídeos , Candida albicans/genética , Técnicas de Cocultura , Cianobactérias/química , Depsipeptídeos/metabolismo , Família MultigênicaRESUMO
Since the late 1970s, many 'omics-style investigations have advanced our understanding of systems at all levels, from community level, through organismal, to individual cellular processes. Beginning with genomics and progressing through transcriptomics, proteomics and finally to metabolomics, the scope of interest shifts significantly from what is genetically possible to what is currently expressed, produced and measurable in a system. While the ideal goal of any 'omics investigation is to fully describe a system, loss of information occurs at each decision-making juncture. These losses are often not considered in the experimental planning stage but, when combined, they drastically affect the power of an investigation and the conclusions that can be drawn from it. Herein we discuss through the analogy of photography many of the decision-making junctures of metabolomics investigations and the resultant losses of information occurring at each.