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
Affiliations
Jing-Rui Liu
Jiangsu Key Laboratory of Pesticide Science, College of Sciences, Nanjing Agricultural University, Nanjing 210095, China
Ya Gao
Jiangsu Key Laboratory of Pesticide Science, College of Sciences, Nanjing Agricultural University, Nanjing 210095, China
Bing Jin
Jiangsu Key Laboratory of Pesticide Science, College of Sciences, Nanjing Agricultural University, Nanjing 210095, China
Dale Guo
State Key Laboratory Breeding Base of Systematic Research Development and Utilization of Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
Fang Deng
State Key Laboratory Breeding Base of Systematic Research Development and Utilization of Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
Qiang Bian
National Pesticide Engineering Research Center (Tianjin), College of Chemistry, Nankai University, Tianjin 300071, China
Hai-Feng Zhang
Department of Plant Pathology, College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China
Xin-Ya Han
School of Chemistry & Chemical Engineering, Anhui University of Technology, Ma’anshan 243002, China
Abdallah S. Ali
Department of Microbiology, Faculty of Agriculture, Cairo University, Giza 12613, Egypt
Ming-Zhi Zhang
Jiangsu Key Laboratory of Pesticide Science, College of Sciences, Nanjing Agricultural University, Nanjing 210095, China
Wei-Hua Zhang
Jiangsu Key Laboratory of Pesticide Science, College of Sciences, Nanjing Agricultural University, Nanjing 210095, China
Yu-Cheng Gu
Syngenta Jealott’s Hill International Research Centre, Bracknell RG42 6EY, Berkshire, UK
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.
