Discovery of Chitin Deacetylase Inhibitors through Structure-Based Virtual Screening and Biological Assays

Yaodong Liu; Sibtain Ahmed; Yaowei Fang; Meng Chen; Jia An; Guang Yang; Xiaoyue Hou; Jing Lu; Qinwen Ye; Rongjun Zhu; Qitong Liu; Shu Liu

doi:10.4014/jmb.2201.01009

Discovery of Chitin Deacetylase Inhibitors through Structure-Based Virtual Screening and Biological Assays

J Microbiol Biotechnol. 2022 Apr 28;32(4):504-513. doi: 10.4014/jmb.2201.01009.

Authors

Yaodong Liu^{1

2}, Sibtain Ahmed³, Yaowei Fang^{1

2

4}, Meng Chen⁵, Jia An^{1

2}, Guang Yang^{1

2}, Xiaoyue Hou^{1

2}, Jing Lu^{1

2}, Qinwen Ye^{1

2}, Rongjun Zhu^{1

2}, Qitong Liu^{1

2}, Shu Liu^{1

2}

Affiliations

¹ Jiangsu Key Laboratory of Marine Bioresources and Environment, Jiangsu Ocean University, Lianyungang, 222005, P.R. China.
² Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Jiangsu Ocean University, Lianyungang 222005, P.R. China.
³ University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
⁴ Jiangsu Marine Resources Development Research Institute, Jiangsu Ocean University, Lianyungang 222000, P.R. China.
⁵ Lianyungang Inspection and Testing Center for Food and Drug Control, P.R. China.

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 soilborne 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 μg/ml and minimum fungicidal concentration (MFC) at 520 μg/ml. Therefore, compound J075-4187 is a good candidate for use in developing antifungal agents for fungi control.

Keywords: Chitin deacetylase; biological assays; enzyme inhibitor; virtual screening.

MeSH terms

Amidohydrolases* / metabolism
Antifungal Agents* / chemistry
Antifungal Agents* / pharmacology
Biological Assay
Chitin / metabolism
Microbial Sensitivity Tests
Molecular Docking Simulation

Substances

Antifungal Agents
Chitin
Amidohydrolases
chitin deacetylase