AUTHOR=Li Lixia , Zhang Yu , Liu Tao , Xing Rui , Peng Shuwei , Song Xu , Zou Yuanfeng , Zhao Xinghong , Jia Renyong , Wan Hongping , Yin Lizi , Ye Gang , Shi Fei , Zhang Yingying , Yue Guizhou , Yin Zhongqiong TITLE=Structural modification of octadecanoic acid-3,4-tetrahydrofuran diester and the acaricidal activity and mechanism of its derivatives against Sarcoptesscabiei var. Cuniculi JOURNAL=Frontiers in Pharmacology VOLUME=Volume 13 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.953284 DOI=10.3389/fphar.2022.953284 ISSN=1663-9812 ABSTRACT=

Octadecanoic acid-3,4-tetrahydrofuran diester is a compound with acaricidal activity isolated and extracted from neem oil. In this study, a series of derivatives were obtained by structural modification of octadecanoic acid-3,4-tetrahydrofuran diester. The acaricidal activity of these derivatives indicated that introduction of benzyloxy substitution at the 2-position of the furan ring and the formation of a benzoate at the 3,4-position of the furan ring (benzoic acid-2-benzyloxy-3,4-tetrahydrofuran diester) could enhance the acaricidal activity. At concentration of 20, 10, and 5 mg/ml, the median lethal time (LT50) values of benzoic acid-2-benzyloxy-3,4-tetrahydrofuran diester were 16.138, 47.274, and 108.122 min, respectively. The LC50 value of benzoic acid-2-benzyloxy-3,4-tetrahydrofuran diester at 60 min was 5.342 mg/ml. Transmission electron microscopy showed that after treatment with benzoic acid-2-benzyloxy-3,4-tetrahydrofuran diester, the body structure of mites was destroyed; dermal organelles were dissolved; nuclear chromatin was ablated. Further, transcriptome sequencing analysis was used to get insight into the acaricidal mechanism of benzoic acid-2-benzyloxy-3,4-tetrahydrofuran diester. The results showed that its acaricidal mechanism is related to interfering “energy metabolism” in S. scabiei, including processes such as citric acid cycle, oxidative phosphorylation pathway and fatty acid metabolism. Additionally, through the activity detection of the mitochondrial complexes of S. scabiei, it was further verified that the acaricidal mechanism of benzoic acid-2-benzyloxy-3,4-tetrahydrofuran diester was related to the energy metabolism system of S. scabiei.