Semisynthetic Sesquiterpene Lactones Generated by the Sensibility of Glaucolide B to Lewis and Brønsted-Lowry Acids and Bases: Cytotoxicity and Anti-Inflammatory Activities.

Autor: da Silva LAL; Post-Graduate Program of Pharmacy, Universidade Federal de Santa Catarina, Campus Universitário-Trindade, Florianópolis CEP 8840-970, SC, Brazil., Sandjo LP; Department of Chemistry, Universidade Federal de Santa Catarina, Campus Universitário-Trindade, Florianópolis CEP 88040-900, SC, Brazil., Assunção LS; Post-Graduate Program of Pharmacy, Universidade Federal de Santa Catarina, Campus Universitário-Trindade, Florianópolis CEP 8840-970, SC, Brazil., Prigol AN; Post-Graduate Program of Pharmacy, Universidade Federal de Santa Catarina, Campus Universitário-Trindade, Florianópolis CEP 8840-970, SC, Brazil., de Siqueira CD; Post-Graduate Program of Pharmacy, Universidade Federal de Santa Catarina, Campus Universitário-Trindade, Florianópolis CEP 8840-970, SC, Brazil., Creczynski-Pasa TB; Department of Pharmaceutical Sciences, Universidade Federal de Santa Catarina, Campus Universitário-Trindade, Florianópolis CEP 88040-970, SC, Brazil., Scotti MT; Post-Graduate Program in Natural and Synthetic Bioactive Products, Universidade Federal da Paraíba, Cidade Universitária-Castelo Branco III, João Pessoa CEP 58051-900, PB, Brazil., Scotti L; Post-Graduate Program in Natural and Synthetic Bioactive Products, Universidade Federal da Paraíba, Cidade Universitária-Castelo Branco III, João Pessoa CEP 58051-900, PB, Brazil., Filippin-Monteiro FB; Department of Clinical Analysis, Universidade Federal de Santa Catarina, Campus Universitário-Trindade, Florianópolis CEP 88040-900, SC, Brazil., Biavatti MW; Department of Pharmaceutical Sciences, Universidade Federal de Santa Catarina, Campus Universitário-Trindade, Florianópolis CEP 88040-970, SC, Brazil.
Jazyk: angličtina
Zdroj: Molecules (Basel, Switzerland) [Molecules] 2023 Jan 27; Vol. 28 (3). Date of Electronic Publication: 2023 Jan 27.
DOI: 10.3390/molecules28031243
Abstrakt: Sesquiterpene lactone (SL) subtypes including hirsutinolide and cadinanolide have a controversial genesis. Metabolites of these classes are either described as natural products or as artifacts produced via the influence of solvents, chromatographic mobile phases, and adsorbents used in phytochemical studies. Based on this divergence, and to better understand the sensibility of these metabolites, different pH conditions were used to prepare semisynthetic SLs and evaluate the anti-inflammatory and antiproliferative activities. Therefore, glaucolide B ( 1 ) was treated with various Brønsted-Lowry and Lewis acids and bases-the same approach was applied to some of its derivatives-allowing us to obtain 14 semisynthetic SL derivatives, 10 of which are hereby reported for the first time. Hirsutinolide derivatives 7a (CC 50 = 5.0 µM; SI = 2.5) and 7b (CC 50 = 11.2 µM; SI = 2.5) and the germacranolide derivative 8a (CC 50 = 3.1 µM; SI = 3.0) revealed significant cytotoxic activity and selectivity against human melanoma SK-MEL-28 cells when compared with that against non-tumoral HUVEC cells. Additionally, compounds 7a and 7c.1 showed strongly reduced interleukin-6 (IL-6) and nitrite (NOx) release in pre-treated M1 macrophages J774A.1 when stimulated with lipopolysaccharide. Despite the fact that hirsutinolide and cadinanolide SLs may be produced via plant metabolism, this study shows that acidic and alkaline extraction and solid-phase purification processes can promote their formation.
Competing Interests: The authors declare no conflicts of interest.
Databáze: MEDLINE
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