Bioactive Brominated Oxindole Alkaloids from the Red Sea Sponge Callyspongia siphonella

Abstract

In the present study, LC-HRESIMS-assisted dereplication along with bioactivity-guided isolation led to targeting two brominated oxindole alkaloids (compounds 1 and 2) which probably play a key role in the previously reported antibacterial, antibiofilm, and cytotoxicity of Callyspongia siphonella crude extracts. Both metabolites showed potent antibacterial activity against Gram-positive bacteria, Staphylococcus aureus (minimum inhibitory concentration (MIC) = 8 and 4 µg/mL) and Bacillus subtilis (MIC = 16 and 4 µg/mL), respectively. Furthermore, they displayed moderate biofilm inhibitory activity in Pseudomonas aeruginosa (49.32% and 41.76% inhibition, respectively), and moderate in vitro antitrypanosomal activity (13.47 and 10.27 µM, respectively). In addition, they revealed a strong cytotoxic effect toward different human cancer cell lines, supposedly through induction of necrosis. This study sheds light on the possible role of these metabolites (compounds 1 and 2) in keeping fouling organisms away from the sponge outer surface, and the possible applications of these defensive molecules in the development of new anti-infective agents.

Discovery of Two Brominated Oxindole Alkaloids as Staphylococcal DNA Gyrase and Pyruvate Kinase Inhibitors via Inverse Virtual Screening

“…The antibacterial evaluation was performed for our small natural products library (Compounds 1-36, Table S1) in terms of MIC values in µM using standard antibacterial agents (ampicillin and gentamicin). The results of inhibitory evaluation along with our previous inhibitory reports on other bacterial strains [19] illustrated that a number of related indole derivatives were the only active compounds. The brominated oxindole derivatives, 5-bromotrisindoline and 6-bromotrisindoline (5-Tris and 6-Tris, respectively; Compounds 1 and 2; Table S1) were the most potent metabolites against Gram-positive bacterial MRSA (MIC 8 and 4 µM, respectively) and B. subtilis (MIC 4 and 4 µM/mL, respectively).…”

“…All compounds used in the present study (Compounds 1-36, Table S1, Supplementary Materials) were isolated from the Red Sea-derived sponge Callyspongia siphonella and its associated microorganisms using multiple chromatographic purification steps and using preparative HPLC (Agilent ® 1260 Infinity, CA, USA) as a final step to obtain these compounds in pure form. The detailed procedure of compounds extraction and isolation were described previously [17][18][19]. All chemical structures of the isolated natural metabolites were determined by analysis of their spectral data (MS and NMR) and comparison with reported literature.…”

“…Natural products derived from marine sources have been showing promising pharmacological effects towards a wide array of molecular targets, and their unusual structural diversity provides a crucial source of lead compounds [16]. We previously reported a number of bioactive metabolites from the Red Sea-derived sponge Callyspongia siphonella and its associated microorganisms (Table S1) [17][18][19]. Notably, the two alkaloids, 5-and 6-bromotrisindoline (5-Tris and 6-Tris, respectively; Compounds 1 and 2, Figure 1) together with some phenolic acid derivatives (Compounds 16-27, Table S1) have shown in vitro antibacterial and antitrypanosomal activities, and cytotoxicity against several tumor cell lines.…”

Recent Advances on Marine Alkaloids from Sponges

“…The intermediate isatin was detected during the biosynthesis of compounds 21 and 22. [23] Two novel double indoles alkaloids 23 and 24 were accessed from marine sponge Lamellomorpha strongylata containing the unusual α-ketovinylamide functionality. [12] Compounds 25 and 26 were firstly isolated from the sponge Spongosorites calcicola.…”

“…The results of Western blotting with IL8 (interleukin 8) assay suggested that non-programmed cell line necrosis triggered to the cytotoxicity by compound 21. [23] γ-Carboline alkaloid 27 displayed strong potency on the L5178Y (murine lymphoma) cell line with ED 50 values of 9.1 μg/mL compared to the positive control kahalalide F (ED 50 = 6.3 μg/mL). Another known compound with β-carboline possessed more potent activity, which meant that the β-carboline played a significant role in cytotoxic towards L5178Y.…”