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. 2019 Aug 9;17(8):465.
doi: 10.3390/md17080465.

Bioactive Brominated Oxindole Alkaloids from the Red Sea Sponge Callyspongia siphonella

Seham S El-Hawary  1 , Ahmed M Sayed  2 , Rabab Mohammed  3 , Hossam M Hassan  3 , Mostafa E Rateb  3   4   5 , Elham Amin  3 , Tarek A Mohammed  6 , Mohamed El-Mesery  7   8 , Abdullatif Bin Muhsinah  9 , Abdulrhman Alsayari  9 , Harald Wajant  7 , Mohamed A Anany  10   11 , Usama Ramadan Abdelmohsen  12
Affiliations

Bioactive Brominated Oxindole Alkaloids from the Red Sea Sponge Callyspongia siphonella

Seham S El-Hawary et al. Mar Drugs. .

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.

Keywords: Callyspongia siphonella; LC-HRESIMS; antibacterial; antibiofilm; anticancer; antitrypanosomal; metabolomic profiling; oxindole alkaloids; tisindoline.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Identified compounds by dereplication with LC-HRESIMS.
Figure 2
Figure 2
1H–1H COSY and key HMBC correlations of compounds 1,2.
Figure 3
Figure 3
Cytotoxic effects of compounds 1 and 2 on human colon cancer (HT-29), human ovarian cancer (OVACR-3), and multiple myeloma (MM.1s) cell lines. The cells were stimulated overnight with increasing concentrations of compounds 1 and 2. on the next day, cellular viability was determined by crystal violet staining for HT-29 and OVACR-3, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for MM.1s.
Figure 4
Figure 4
Morphological changes of HT-29, OVCAR-3, and MM.1S cells incubated overnight with compound (1) (20 µM) in comparison to untreated cells using an EVOS FL digital microscope.
Figure 5
Figure 5
Western blotting analysis of 1 against beclin and caspase 3, the key proteins of autophagy and apoptosis, respectively.
See this image and copyright information in PMC

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