Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Discovery of Chitin Deacetylase Inhibitors through Structure-Based Virtual Screening and Biological Assays

  • Liu, Yaodong (Jiangsu Key Laboratory of Marine Bioresources and Environment, Jiangsu Ocean University) ;
  • Ahmed, Sibtain (University of California San Diego) ;
  • Fang, Yaowei (Jiangsu Key Laboratory of Marine Bioresources and Environment, Jiangsu Ocean University) ;
  • Chen, Meng (Lianyungang Inspection and Testing Center for Food and Drug Control) ;
  • An, Jia (Jiangsu Key Laboratory of Marine Bioresources and Environment, Jiangsu Ocean University) ;
  • Yang, Guang (Jiangsu Key Laboratory of Marine Bioresources and Environment, Jiangsu Ocean University) ;
  • Hou, Xiaoyue (Jiangsu Key Laboratory of Marine Bioresources and Environment, Jiangsu Ocean University) ;
  • Lu, Jing (Jiangsu Key Laboratory of Marine Bioresources and Environment, Jiangsu Ocean University) ;
  • Ye, Qinwen (Jiangsu Key Laboratory of Marine Bioresources and Environment, Jiangsu Ocean University) ;
  • Zhu, Rongjun (Jiangsu Key Laboratory of Marine Bioresources and Environment, Jiangsu Ocean University) ;
  • Liu, Qitong (Jiangsu Key Laboratory of Marine Bioresources and Environment, Jiangsu Ocean University) ;
  • Liu, Shu (Jiangsu Key Laboratory of Marine Bioresources and Environment, Jiangsu Ocean University)
  • Received : 2022.01.11
  • Accepted : 2022.02.03
  • Published : 2022.04.28
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Abstract

Chitin deacetylase (CDA) inhibitors were developed as novel antifungal agents because CDA participates in critical fungal physiological and metabolic processes and increases virulence in soil-borne fungal pathogens. However, few CDA inhibitors have been reported. In this study, 150 candidate CDA inhibitors were selected from the commercial Chemdiv compound library through structure-based virtual screening. The top-ranked 25 compounds were further evaluated for biological activity. The compound J075-4187 had an IC50 of 4.24 ± 0.16 µM for AnCDA. Molecular docking calculations predicted that compound J075-4187 binds to the amino acid residues, including active sites (H101, D48). Furthermore, compound J075-4187 inhibited food spoilage fungi and plant pathogenic fungi, with minimum inhibitory concentration (MIC) at 260 ㎍/ml and minimum fungicidal concentration (MFC) at 520 ㎍/ml. Therefore, compound J075-4187 is a good candidate for use in developing antifungal agents for fungi control.

Keywords

Acknowledgement

This work was supported by the National Natural Science Foundation of China (Grant no. 31772016), Jiangsu Province Marine Science and Technology Innovation Project (HY2018-10), the Priority Academic Program Development of Jiangsu Higher Education Institutions, Project "333" of Jiangsu Province, Open-end Funds of Jiangsu Key Laboratory of Marine Bioresources and Environment (SH20191204), and Jiangsu Postgraduate Practice Innovation Program (SJCX20_1303).

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