The Discovery of Antibacterial Natural Compound Based on Peptide Deformylase

Title:The Discovery of Antibacterial Natural Compound Based on Peptide Deformylase

Volume: 21 Issue: 4

Author(s): Li Liang, Qianqian Zhou, Zhixiang Hao, Fanfan Wang, Yasheng Zhu, Qisi Lin*Jian Gao*

Affiliation:

• Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu 221004,China

• Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu 221004,China

Keywords: Peptide deformylase, traditional Chinese medicine database, high-throughput virtual screening, molecular docking, antibacterial drug, computer-aided drug design.

Abstract: Background: In recent years, Staphylococcus aureus have developed resistance to medicines used for the treatment of human infections. Therefore, the search for antibacterial agents of high potency against Staphylococcus aureus is of great concern. Peptide deformylase (PDF), a metalloprotease catalyzing the removal of a formyl group from newly synthesized proteins, has been considered to be an important antibacterial drug target.

Objective: To discover novel antibacterial drugs based on Staphylococcus aureus peptide deformylase.

Method: PDF-based virtual screening of compounds from Traditional Chinese Medicine Database@Taiwan was performed by Sybyl X2.1 Surflex dock software. Compounds which possess high docking score were used for the following antibacterial experiments to evaluate their antibacterial activities. Kanamycin was also used in the antibacterial experiment as a control substance in the assay. Furthermore, molecular docking studies was applied to elucidate binding interaction between some compounds and PDF. In silico pharmacokinetic and toxicity prediction was explored to explain the reasons why these compounds might stand good chance of providing some pharmaceutical benefits.

Results: Gentiopicroside, protosappanin B, dihydromyricetin and cryptochlorogenic acid with high docking score were used for our subsequent antibacterial assays. The Minimum Inhibitory Concentration (MIC) of kanamycin and gentiopicroside were 0.008 mg·mL-1 and 0.431 mg·mL-1, respectively, other three compounds, protosappanin B, dihydromyricetin and cryptochlorogenic acid have close MIC value of 0.50 mg·mL-1.

Conclusion: Dihydromyricetin, with the MIC value of 0.50 mg·mL-1 and relatively high drug score of 0.82, may serve as a novel antibacterial lead compound.

Cite this article as:

Liang Li , Zhou Qianqian , Hao Zhixiang , Wang Fanfan , Zhu Yasheng, Lin Qisi *, Gao Jian*, The Discovery of Antibacterial Natural Compound Based on Peptide Deformylase, Combinatorial Chemistry & High Throughput Screening 2018; 21 (4) . https://dx.doi.org/10.2174/1386207321666180220124259