Marine Drugs (Jan 2023)

Design, Synthesis, Antifungal Activity, and Molecular Docking of Streptochlorin Derivatives Containing the Nitrile Group

  • Jing-Rui Liu,
  • Ya Gao,
  • Bing Jin,
  • Dale Guo,
  • Fang Deng,
  • Qiang Bian,
  • Hai-Feng Zhang,
  • Xin-Ya Han,
  • Abdallah S. Ali,
  • Ming-Zhi Zhang,
  • Wei-Hua Zhang,
  • Yu-Cheng Gu

DOI
https://doi.org/10.3390/md21020103
Journal volume & issue
Vol. 21, no. 2
p. 103

Abstract

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Based on the structures of natural products streptochlorin and pimprinine derived from marine or soil microorganisms, a series of streptochlorin derivatives containing the nitrile group were designed and synthesized through acylation and oxidative annulation. Evaluation for antifungal activity showed that compound 3a could be regarded as the most promising candidate—it demonstrated over 85% growth inhibition against Botrytis cinerea, Gibberella zeae, and Colletotrichum lagenarium, as well as a broad antifungal spectrum in primary screening at the concentration of 50 μg/mL. The SAR study revealed that non-substituent or alkyl substituent at the 2-position of oxazole ring were favorable for antifungal activity, while aryl and monosubstituted aryl were detrimental to activity. Molecular docking models indicated that 3a formed hydrogen bonds and hydrophobic interactions with Leucyl-tRNA Synthetase, offering a perspective for the possible mechanism of action for antifungal activity of the target compounds.

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