Natural product protulactone A: Total synthesis from D-galactose, X-ray analysis and biological evaluation

[Display omitted] •Protulactone A.•Natural product.•X-ray analysis.•Antiproliferative activity. Synthesis of protulactone A (PLA, 1) and twelve of its analogues have been achieved starting from d-galactose. PLA was isolated in the crystalline state, and its crystal structure was determined utilizing...

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Bibliographic Details
Published in:Bioorganic chemistry 2022-10, Vol.127, p.105980-105980, Article 105980
Main Authors: Djokić, Sanja, Francuz, Jovana, Popsavin, Mirjana, Rodić, Marko V., Kojić, Vesna, Stevanović, Milena, Popsavin, Velimir
Format: Article
Language:English
Subjects:
Antimicrobial activity
Antiproliferative activity
Bicyclic lactone
Natural product
Protulactone A
X-ray analysis
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Summary:[Display omitted] •Protulactone A.•Natural product.•X-ray analysis.•Antiproliferative activity. Synthesis of protulactone A (PLA, 1) and twelve of its analogues have been achieved starting from d-galactose. PLA was isolated in the crystalline state, and its crystal structure was determined utilizing X-ray crystallography, which confirmed the assumed stereochemistry at all stereocenters. All tested compounds displayed antiproliferative activity against a panel of tumour cell lines, and all of them were non-cytotoxic toward the normal cells (MRC-5). Natural product PLA (1) was the most active against the K562 and MCF-7 cell lines (IC50 6.52 and 2.20 μM, respectively). Some of the synthesized derivatives showed very potent cytotoxicity, especially analogues 11, 13 and 15 (IC50 1.08–1.14 μM against MCF-7), and 9 and 14 (IC50 1.29 and 1.64 μM against K562). SAR analysis indicated important structural motifs for antiproliferative activity. Unfortunately, PLA (1), its C-7 epimer (2) and demethylated analogue (3) did not display a significant antimicrobial activity (two Gram-positive and two Gram-negative bacteria and one fungal strain) and they also cannot affect the ability to modulate bacterial communication.
ISSN:0045-2068
1090-2120
DOI:10.1016/j.bioorg.2022.105980