New from Old: Thorectandrin Alkaloids in a Southern Australian Marine Sponge, Thorectandra choanoides (CMB-01889)
| Autor: | Robert J. Capon, Laizuman Nahar, Angela A. Salim, Ahmed H. Elbanna, Shamsunnahar Khushi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
indoleamine 2
3-dioxygenase Stereochemistry Pharmaceutical Science Conjugated system Thorectandra choanoides 01 natural sciences tryptophan alkaloid 03 medical and health sciences Drug Discovery Reactivity (chemistry) Pharmacology Toxicology and Pharmaceutics (miscellaneous) lcsh:QH301-705.5 030304 developmental biology chemistry.chemical_classification 0303 health sciences biology 010405 organic chemistry Chemistry Alkaloid biology.organism_classification 0104 chemical sciences aplysinopsins Sponge Transformation (genetics) Enzyme lcsh:Biology (General) GNPS molecular network Michael reaction Pharmacophore |
| Zdroj: | Marine Drugs, Vol 19, Iss 97, p 97 (2021) Marine Drugs Volume 19 Issue 2 |
| ISSN: | 1660-3397 |
| Popis: | Thorectandra choanoides (CMB-01889) was prioritized as a source of promising new chemistry from a library of 960 southern Australian marine sponge extracts, using a global natural products social (GNPS) molecular networking approach. The sponge was collected at a depth of 45 m. Chemical fractionation followed by detailed spectroscopic analysis led to the discovery of a new tryptophan-derived alkaloid, thorectandrin A (1), with the GNPS cluster revealing a halo of related alkaloids 1a–1n. In considering biosynthetic origins, we propose that Thorectandrachoanoides (CMB-01889) produces four well-known alkaloids, 6-bromo-1′,8-dihydroaplysinopsin (2), 6-bromoaplysinopsin (3), aplysinopsin (4), and 1′,8-dihydroaplysinopsin (10), all of which are susceptible to processing by a putative indoleamine 2,3-dioxygenase-like (IDO) enzyme to 1a–1n. Where the 1′,8-dihydroalkaloids 2 and 10 are fully transformed to stable ring-opened thorectandrins 1 and 1a–1b, and 1h–1j, respectively, the conjugated precursors 3 and 4 are transformed to highly reactive Michael acceptors that during extraction and handling undergo complete transformation to artifacts 1c–1g, and 1k–1n, respectively. Knowledge of the susceptibility of aplysinopsins as substrates for IDOs, and the relative reactivity of Michael acceptor transformation products, informs our understanding of the pharmaceutical potential of this vintage marine pharmacophore. For example, the cancer tissue specificity of IDOs could be exploited for an immunotherapeutic response, with aplysinopsins transforming in situ to Michael acceptor thorectandrins, which covalently bind and inhibit the enzyme. |
| Databáze: | OpenAIRE |
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