Sulfated steroid-amino acid conjugates from the Irish marine sponge Polymastia boletiformis.

Vangelis Smyrniotopoulos,Christina Coleman,Carsten Wolff,Deniz Tasdemir,Margaret Rae,Grace Mccormack,Yuanqing Ding,Sylvia Soldatou,Daneel Ferreira

doi:10.3390/md13041632

Vangelis Smyrniotopoulos, Christina Coleman + Show 7 more

Open Access

https://doi.org/10.3390/md13041632

Copy DOI

Abstract

Antifungal bioactivity-guided fractionation of the organic extract of the sponge Polymastia boletiformis, collected from the west coast of Ireland, led to the isolation of two new sulfated steroid-amino acid conjugates (1 and 2). Extensive 1D and 2D NMR analyses in combination with quantum mechanical calculations of the electronic circular dichroism (ECD) spectra, optical rotation, and 13C chemical shifts were used to establish the chemical structures of 1 and 2. Both compounds exhibited moderate antifungal activity against Cladosporium cucumerinum, while compound 2 was also active against Candida albicans. Marine natural products containing steroidal and amino acid constituents are extremely rare in nature.

Highlights

Marine sponges (Porifera) are primitive filter-feeders, yet they represent the richest and best studied sources of novel marine bioactive natural products [1]
CH2Cl2/MeOH extract of the freeze-dried sponge was subjected to a modified Kupchan partitioning scheme to yield n-hexane, CHCl3, and aqueous MeOH subextracts
Bioassay-guided separation of the antifungal aqueous MeOH-soluble fraction, which included a combination of C18 reversed-phase flash column chromatography (RP-FCC), Sephadex LH-20 size-exclusion chromatography, and repeated

Summary

Introduction

Marine sponges (Porifera) are primitive filter-feeders, yet they represent the richest and best studied sources of novel marine bioactive natural products [1]. The declining number and efficacy of existing antifungal agents, the increased occurrence of systemic fungal infections, and rapid emergence of drug resistance underline the necessity for the discovery of new antifungal drug leads. This report describes the bioactivity-guided isolation and structure elucidation of two new, minor sulfated steroid-amino acid conjugates, 1, and its 7-methoxy derivative, 2 (Figure 1). Both compounds feature linkage of the non-proteinaceous α-amino acid p-methoxyphenylglycine with 4,24-dimethyl-3-O-sulfocholest-8(14),25(26)-dien-27-oic acid, via an amide bond. The molecular structures of the natural products were established on the basis of 1D and

Results and Discussion

General Experimental Procedures

Biological Material

Extraction and Isolation

Conclusions

41. Sponge sterols