Design, synthesis, and mechanism study of novel tetrahydroisoquinoline derivatives as antifungal agents.

IF 3.9 2区化学 Q2 CHEMISTRY, APPLIED

Molecular Diversity Pub Date : 2024-10-11 DOI:10.1007/s11030-024-11012-6

Yang Chen, YanXi Jin, LuYao Wang, WanXiang Wang, HaiPing Zhou, Wei Chen

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Abstract

In screening for natural-derived fungicides, a series of 32 novel tetrahydroisoquinoline derivatives were designed and synthesized based on tetrahydroisoquinoline alkaloids. Their structures were verified by ¹H NMR, ¹³C NMR, HRMS, and single X-ray crystal diffraction analysis. Most of the target products exhibited medium to excellent antifungal activity against 6 phytopathogenic fungi in vitro at a concentration of 50 mg/L. Interestingly, compounds A13 and A25 with EC₅₀ values of 2.375 and 2.251 mg/L against A. alternate were similar to boscalid (EC₅₀ = 1.195 mg/L). The in vivo experiments revealed that A13 presented 51.61 and 70.97% protection activities against A. alternate at the dosage of 50 and 100 mg/L, respectively, which were equal to that of boscalid (64.52 and 77.42%). SDH enzyme assays and molecular docking studies indicated that compound A13 may act on SDH. In addition, the SEM analysis showed that compound A13 could strongly damage the mycelium morphology. These results revealed that A13 may be a promising lead compound for the development of natural-derived fungicides.

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新型四氢异喹啉衍生物作为抗真菌剂的设计、合成和机理研究。

在筛选天然来源杀菌剂的过程中，以四氢异喹啉生物碱为基础，设计并合成了一系列 32 种新型四氢异喹啉衍生物。通过 1H NMR、13C NMR、HRMS 和单 X 射线晶体衍射分析验证了它们的结构。大多数目标产物在体外 50 mg/L 的浓度下对 6 种植物病原真菌具有中等到极佳的抗真菌活性。有趣的是，化合物 A13 和 A25 对互生菌的 EC50 值分别为 2.375 毫克/升和 2.251 毫克/升，与 Boscalid（EC50 = 1.195 毫克/升）相似。体内实验表明，A13 在 50 mg/L 和 100 mg/L 的剂量下对交替蚁的保护活性分别为 51.61% 和 70.97%，与啶虫脒的保护活性（64.52% 和 77.42%）相当。SDH 酶测定和分子对接研究表明，化合物 A13 可能对 SDH 起作用。此外，扫描电镜分析表明，化合物 A13 能强烈破坏菌丝的形态。这些结果表明，A13 可能是开发天然来源杀菌剂的一种有前景的先导化合物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Diversity 化学-化学综合

CiteScore

7.30

自引率

7.90%

发文量

219

审稿时长

2.7 months

期刊介绍： Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including: combinatorial chemistry and parallel synthesis; small molecule libraries; microwave synthesis; flow synthesis; fluorous synthesis; diversity oriented synthesis (DOS); nanoreactors; click chemistry; multiplex technologies; fragment- and ligand-based design; structure/function/SAR; computational chemistry and molecular design; chemoinformatics; screening techniques and screening interfaces; analytical and purification methods; robotics, automation and miniaturization; targeted libraries; display libraries; peptides and peptoids; proteins; oligonucleotides; carbohydrates; natural diversity; new methods of library formulation and deconvolution; directed evolution, origin of life and recombination; search techniques, landscapes, random chemistry and more;