Subereamolline A as a Potent Breast Cancer Migration, Invasion and Proliferation Inhibitor and Bioactive Dibrominated Alkaloids from the Red Sea Sponge Pseudoceratina arabica

Abstract

A new collection of several Red Sea sponges was investigated for the discovery of potential breast cancer migration inhibitors. Extracts of the Verongid sponges Pseudoceratina arabica and Suberea mollis were selected. Bioassay-directed fractionation of both sponges, using the wound-healing assay, resulted into the isolation of several new and known brominated alkaloids. Active fractions of the sponge Pseudoceratina arabica afforded five new alkaloids, ceratinines A–E (2–6), together with the known alkaloids moloka’iamine (1), hydroxymoloka’iamine (7) and moloka’iakitamide (8). The active fraction of the sponge Suberea mollis afforded the three known alkaloids subereamolline A (9), aerothionin (10) and homoaerothionin (11). Ceratinine B (3) possesses an unprecedented 5,7-dibrominated dihydroindole moiety with an epoxy ring on the side chain of a fully substituted aromatic moiety. Ceratinines D (5) and E (6) possess a terminal formamide moiety at the ethylamine side chain. Subereamolline A (9) potently inhibited the migration and invasion of the highly metastatic human breast cancer cells MDA-MB-231 at the nanomolar doses. Subereamolline A and related brominated alkaloids are novel scaffolds appropriate for further future use for the control of metastatic breast cancer.

Isolation and structure elucidation of natural products of three soft corals and a sponge from the coast of Madagascar

“…Samples of the sponge P. arabica from the Red Sea have already been investigated for their chemical constituents, resulting in the isolation of brominated compounds derived from tyrosine. [73][74][75] Specimens of P. arabica were obtained from the waters around Nosy Be, Madagascar, at a depth of about 18-25 m. The samples were homogenized and then extracted with methanol at room temperature. The combined organic layers were filtered and concentrated in vacuo to obtain the crude methanol extract, which was extracted with hexane and then dichloromethane.…”

“…83,87,89 Separation of the two diastereoisomers by HPLC was achieved by Lin and coworkers 91 and Santalova et al, 81 who also provided 1 H NMR data for the separated isomers. Even though the sponge P. arabica has already been investigated for its chemical constituents, [73][74][75] compounds 14a and 14b have not been isolated from this species so far.…”

“…84,86,88,89 In contrast, the parent ketone and related derivatives are described to be active against a variety of pathogens. 73,88,89,92 Some derivatives show antimigratory activity against the highly metastatic MDA-MB-231 human breast cancer cell line, 74,75 induce apoptosis in human breast tumor cells, 93 or inhibit Na + -K + -ATPase activity. 94 It can be assumed that some as yet unidentified components, possibly also dibromotyrosine derivatives, are responsible for the antimicrobial activity of the extracts.…”

New Antimicrobial Bromotyrosine Analogues from the Sponge Pseudoceratina purpurea and Its Predator Tylodina corticalis

“…Sponges of the order Verongida are unique in the Demospongiae as the only group that contains alkaloids derived from bromotyrosine and sterols of the aplystane type; these are distinct chemotaxonomic markers for all the verongid genera [ 1 , 2 , 3 ]. The alkaloids have been reported to have antimicrobial [ 4 , 5 , 6 , 7 ], antifungal [ 8 , 9 ], cytotoxic [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ], and antimalarial [ 22 , 23 , 24 ] activity for example and many have unique modes of action. Consequently, verongid sponges have no natural predators other than a few specialised molluscs such as nudibranchs [ 25 ].…”

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“…Subereamolline A and related brominated alkaloids could be considered as scaffolds appropriate for extensive future use for the control of metastatic breast cancer. 73 …”