Zeylleucapenoids A–D, Highly Oxygenated Diterpenoids with Anti-Inflammatory Activity from Leucas zeylanica (L.) R. Br.
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Published:2023-05-31
Issue:11
Volume:28
Page:4472
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ISSN:1420-3049
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Container-title:Molecules
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language:en
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Short-container-title:Molecules
Author:
Zhao Ting12,
Zhang Xuan12,
Nong Xu-Hua12,
Zhou Xue-Ming12,
Chai Ru-Ru12,
Li Xiao-Bao12,
Chen Guang-Ying12
Affiliation:
1. Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education Hainan Normal University, Haikou 571158, China
2. Key Laboratory of Tropical Medicinal Plant Chemistry of Hainan Province, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou 571158, China
Abstract
Four previously undescribed highly oxygenated diterpenoids (1–4), zeylleucapenoids A–D, characterized by halimane and labdane skeletons, were isolated from the aerial parts of Leucas zeylanica. Their structures were elucidated primarily via NMR experiments. The absolute configuration of 1 was established using theoretical ECD calculations and X-ray crystallographic analysis, whereas those for 2–4 were assigned using theoretical ORD calculations. Zeylleucapenoids A–D were tested for anti-inflammatory activity against nitric oxide (NO) production in RAW264.7 macrophages, of which only 4 showed significant efficacy with an IC50 value of 38.45 μM. Further, active compound 4 was also evaluated for the inhibition of the release of pro-inflammatory cytokines TNF-α and IL-6 and was found to have a dose-dependent inhibitory effect, while it showed nontoxic activity for zebrafish embryos. A subsequent Western blotting experiment revealed that 4 inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, molecular docking analysis indicated that the possible mechanism of action for 4 may be bind to targets via hydrogen and hydrophobic bond interactions.
Funder
Key R&D Projects in Hainan Province-Social Development
National Natural Science Foundation of China
Innovation Platform for Academicians of Hainan Province
Central Government Guides Local Science and Technology Development
innovative research project of Hainan Graduate students
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science