Buljan, Anđela; Stepanić, Višnja; Čikoš, Ana; Babić, Sanja; Bojanić, Krunoslav; Roje, Marin (2024) Total Synthesis and Biological Profiling of Putative (±)-Marinoaziridine B and (±)-N-Methyl Marinoaziridine A. Marine Drugs, 22 (7). ISSN 1660-3397
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Abstract
The total synthesis of two new marine natural products, (±)-marinoaziridine B 7 and (±)-N-methyl marinoaziridine A 8, was accomplished. The (±)-marinoaziridine 7 was prepared in a six-step linear sequence with a 2% overall yield. The key steps in our strategy were the preparation of the chiral epoxide (±)-5 using the Johnson Corey Chaykovsky reaction, followed by the ring-opening reaction and the Staudinger reaction. The N,N-dimethylation of compound (±)-7 gives (±)-N-methyl marinoaziridine A 8. The NMR spectra of synthetized (±)-marinoaziridine B 7 and isolated natural product did not match. The compounds are biologically characterized using relevant in silico, in vitro and in vivo methods. In silico ADMET and bioactivity profiling predicted toxic and neuromodulatory effects. In vitro screening by MTT assay on three cell lines (MCF-7, H-460, HEK293T) showed that both compounds exhibited moderate to strong antiproliferative and cytotoxic effects. Antimicrobial tests on bacterial cultures of Escherichia coli and Staphylococcus aureus demonstrated the dose-dependent inhibition of the growth of both bacteria. In vivo toxicological tests were performed on zebrafish Danio rerio and showed a significant reduction of zebrafish mortality due to N-methylation in (±)-8.
| Item Type: | Article | ||||||||
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| Uncontrolled Keywords: | marinoaziridines; total synthesis; antibacterial activity; antiproliferative activity; cytotoxicity; bioactivity profiling; ADMET; in silico activity; marine natural products | ||||||||
| Subjects: | NATURAL SCIENCES > Chemistry NATURAL SCIENCES > Chemistry > Organic Chemistry NATURAL SCIENCES > Interdisciplinary Natural Sciences NATURAL SCIENCES > Interdisciplinary Natural Sciences > Marine Science |
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| Divisions: | Division of Organic Chemistry and Biochemistry Division of Experimental Physics Division of Materials Chemistry NMR Center |
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| Depositing User: | Marin Roje | ||||||||
| Date Deposited: | 15 Jan 2025 10:11 | ||||||||
| URI: | http://fulir.irb.hr/id/eprint/9463 | ||||||||
| DOI: | 10.3390/md22070310 |
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