New from Old: Thorectandrin Alkaloids in a Southern Australian Marine Sponge, Thorectandra choanoides (CMB-01889)

Abstract

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.

Good Practices in Sponge Natural Product Studies: Revising Vouchers with Isomalabaricane Triterpenes

“…Guidelines in Marine Drugs and Molecules (both MDPI publications) are identical and only refer to “ research involving plants ”, with no mention of marine organisms. Although MDPI guidelines request GPS coordinates of the locality and that “ voucher specimens must be deposited in an accessible herbarium or museum ”, some sponge NP articles from these journals do not follow these guidelines [ 75 , 76 , 77 ]. Phytochemistry Letters has clear guidelines in terms of deposition of the plant vouchers in an herbarium, checking the validity of the species name and including an illustration if the species is poorly known.…”

Glenthenamines A–F: Enamine Pyranonaphthoquinones from the Australian Pasture Plant Derived Streptomyces sp. CMB-PB042

“…CMB-F563, 11,12 and thorectandrins from the southern Australian marine sponge Thorectandra choanoides (CMB-01889). 13 In light of this, we were alerted to the possibility that one or more of the glenthenamines may be artifacts. This suspicion was confirmed when UPLC-QTOF single-ion extraction (SIE) analysis of fresh EtOAc extracts from agar plate cultivation of Streptomyces sp.…”

“…CMB-F713, the prolinimines and N -amino- L -proline methyl ester from the fish gut-derived fungus Evlachovaea sp. CMB-F563, , and thorectandrins from the southern Australian marine sponge Thorectandra choanoides (CMB-01889) . In light of this, we were alerted to the possibility that one or more of the glenthenamines may be artifacts.…”

“…Nuclear magnetic resonance (NMR) spectra were acquired on a Bruker Avance 600 MHz spectrometer with either a 5 mm PASEL 1 H/D-13 C Z-Gradient probe or 5 mm CPTCI 1 H/ 19 F− 13 C/ 15 N/DZ-Gradient cryoprobe. In all cases, spectra were acquired at 25 °C in DMSO-d 6 with referencing to residual 1 H or 13 C signals (DMSO-d 6 , δ H 2.50 and δ C 39.5). Highresolution ESIMS spectra were obtained on a Bruker micrOTOF mass spectrometer by direct injection in MeOH at 3 μL/min using sodium formate clusters as an internal calibrant.…”

Glenthenamines A–F: Enamine pyranonaphthoquinones from the Australian pasture plant-derived Streptomyces sp. CMB-PB042

“…Nuclear magnetic resonance (NMR) spectra were acquired on a Bruker Avance 600 MHz spectrometer with either a 5 mm PASEL 1 H/D-13 C Z-Gradient probe or 5 mm CPTCI 1 H/ 19 F-13 C/ 15 N/DZ-Gradient cryoprobe. In all cases spectra were acquired at 25 °C in DMSO-d6 with referencing to residual 1 H or 13 C signals (DMSO-d6, dH 2.50 and dC 39.5). High-resolution ESIMS spectra were obtained on a Bruker micrOTOF mass spectrometer by direct injection in MeOH at 3 μL/min using sodium formate clusters as an internal calibrant.…”