Discovery and isolation of novel capsaicinoids and their TRPV1-related activity

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 3, 2024

Abstract Chilis contain capsaicin, an acclaimed molecule in both science and culinary ventures. Capsaicin’s target protein, the transient receptor potential cation channel subfamily V member 1 (TRPV1), has been linked to many post-activation effects, including changes metabolism pain sensation. Beneficial effects of TRPV1 activation by capsaicin have explored through clinical trials. Capsaicinoids other than also bind TRPV1, but current studies often disregard non-capsaicin interactions. To fill these gaps, we screened 40 different chili varieties derived from four Capsicum species means untargeted metabolomics a rat (rTRPV1) calcium influx assay. The resulting capsaicinoid profiles were specific each variety only partially corresponded with delimitations. Based on rTRPV1 elicited crude extracts, capsaicinoids act synergistic manner profile can serve as gauge this activation. In addition, isolated eighteen capsaicinoids, five previously unreported ones, confirmed their structure NMR MS/MS. We then tested 23 three related compounds. This testing revealed that even slight deviations reduce ability activate target, mere single hydroxylation acyl tail reducing potency towards more 100-fold. how activity presence together non-activating analogs weakly activating found classes molecules positively modulate capsaicin. demonstrates such compounds measurable pharmacological making case for use study natural extracts.

Язык: Английский

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Remarkable diversity of alkaloid scaffolds inPiper fimbriulatum

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 12, 2024

Plant specialized metabolites play key roles in diverse physiological processes and ecological interactions. Identifying structurally novel metabolites, as well discovering known compounds new species, is often crucial for answering broader biological questions. The Piper genus (Piperaceae family) its special phytochemistry has been extensively studied over the past decades. Here, we investigated alkaloid diversity of fimbriulatum, a myrmecophytic plant native to Central America, using metabolomics workflow that combines untargeted LC-MS/MS analysis with range recently-developed computational tools. Specifically, leverage open MS/MS spectral libraries data repositories metabolite annotation, guiding isolation efforts towards structurally-new (i.e., dereplication). As result, identified several alkaloids belonging 5 different classes isolated one seco-benzylisoquinoline featuring linear quaternary amine moiety named fimbriulatumine. Notably, many were never reported Piperaceae plants. Our findings expand this family, demonstrate value revisiting well-studied families state-of-the-art workflows uncover previously overlooked chemodiversity. To contextualize our into context, employed automated mining literature reports scaffolds mapped results onto angiosperm tree life. By doing so, highlight remarkable within provide framework generating hypotheses on biosynthetic evolution these metabolites. Many tools resources used study remain underutilized science community. This manuscript demonstrates their potential through practical application aims promote accessibility approaches.

Язык: Английский

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Antiprotozoal Natural Products from Endophytic Fungi Associated with Cacao and Coffee

Metabolites, Год журнала: 2024, Номер 14(11), С. 575 - 575

Опубликована: Окт. 25, 2024

Collectively, leishmaniasis and Chagas disease cause approximately 8 million cases more than 40,000 deaths annually, mostly in tropical subtropical regions. The current drugs used to treat these diseases have limitations many undesirable side effects; hence, new with better clinical profiles are needed. Fungal endophytes associated plants known produce a wide array of bioactive secondary metabolites, including antiprotozoal compounds. In this study, we analyzed endophytic fungal isolates

Язык: Английский

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