Oligomeric phloroglucinols with hAChE inhibitory and antibacterial activities from tropic Rhodomyrtus tomentosa.

Autor: Luo EE; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China; University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China., Liu SN; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China; University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China., Wang ZJ; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China; Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, Yunnan Characteristic Plant Extraction Laboratory, School of Chemical Science and Technology, Yunnan University, Kunming 650500, People's Republic of China., Chen LY; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China; College of Pharmacy, Guilin Medical University, Guilin 541199, People's Republic of China., Liang CQ; College of Pharmacy, Guilin Medical University, Guilin 541199, People's Republic of China., Yu MY; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China. Electronic address: yumuyuan@mail.kib.ac.cn., Qin XJ; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China; University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China. Electronic address: qinxujie@mail.kib.ac.cn.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2023 Dec; Vol. 141, pp. 106836. Date of Electronic Publication: 2023 Sep 09.
DOI: 10.1016/j.bioorg.2023.106836
Abstrakt: Alzheimer's diseases (AD) and other infectious diseases caused by drug-resistance bacteria have posed a serious threat to human lives and global health. With the aim to search for human acetylcholinesterase (hAChE) inhibitors and antibacterial agents from medicinal plants, 16 phloroglucinol oligomers, including two new phloroglucinol monomers (1a and 1b), four new phloroglucinol dimers (3a, 3b, 4b, and 5a), six new phloroglucinol trimers (6a, 6b, 7a, 7b, 8a, and 8b), and two naturally occurring phloroglucinol monomers (2a and 2b), along with two known congeners (4a and 5b), were purified from the leaves of tropic Rhodomyrtus tomentosa. The structures and absolute configurations of these new isolates were unequivocally established by comprehensive analyses of their spectroscopic data (NMR and HRESIMS), ECD calculation, and single crystal X-ray diffraction. Structurally, 3a/3b shared a rare C-5' formyl group, whereas 6a/6b possessed a unique C-7' aromatic ring. In addition, 7a/7b and 8a/8b were rare phloroglucinol trimers with a bis-furan and a C-6' hemiketal group. Pharmacologically, the mixture of 3a and 3b showed the most potent human acetylcholinesterase (hAChE) inhibitory activity with an IC 50 value of 1.21 ± 0.16 μM. The molecular docking studies of 3a and 3b in the hAChE binding sites were performed, displaying good agreement with the in vitro inhibitory effects. In addition, the mixture of 3a and 3b displayed the most significant anti-MRSA (methicillin-resistant Staphylococcus aureus) with MIC and MBC values of both 0.50 μg/mL, and scanning electron microscope (SEM) studies revealed that they could destroy the biofilm structures of MRSA. The findings provide potential candidates for the further development of anti-AD and anti-bacterial agents.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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