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Synthesis 2023; 55(13): 2099-2108
DOI: 10.1055/a-2023-0028
paper
Special Issue Honoring Prof. Guoqiang Lin's Contributions to Organic Chemistry

Derivatization of Dihydropyrrolidone-Thiadiazole Heterocyclic Compounds and an Evaluation of their Antibacterial and Anti-Biofilm Activities

Chen Xuecheng‡
a   College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, P. R. of China
,
Xiong Yanpeng‡
a   College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, P. R. of China
b   Department of Infectious Diseases and the Key Lab of Endogenous Infection, Shenzhen Nanshan People’s Hospital, the 6th Affiliated Hospital of Shenzhen University Medical School, Shenzhen 518052, P. R. of China
,
Luo Yue
a   College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, P. R. of China
,
Peng Yalan
a   College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, P. R. of China
,
Chen Zhong
b   Department of Infectious Diseases and the Key Lab of Endogenous Infection, Shenzhen Nanshan People’s Hospital, the 6th Affiliated Hospital of Shenzhen University Medical School, Shenzhen 518052, P. R. of China
,
Yu Zhijian∗
b   Department of Infectious Diseases and the Key Lab of Endogenous Infection, Shenzhen Nanshan People’s Hospital, the 6th Affiliated Hospital of Shenzhen University Medical School, Shenzhen 518052, P. R. of China
,
Han Shiqing∗
a   College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, P. R. of China
› Author AffiliationsWe thank The Jiangsu Synergetic Innovation Center for Advanced Bio-Manufacture (Grant no. XTD2210), the National Natural Science Foundation of China (Grant no. 82172283), the Natural Science Foundation of Guangdong Province, China (Grant no. 2021A1515011727), the Science, Technology, and Innovation Commission of Shenzhen Municipality, Key Funds and Basic Research Funds (Grant nos. JCYJ20220530141614034, JCYJ20180508162403996 and JCYJ20180302144403714), and the Shenzhen Key Medical Discipline Construction Fund (Grant no. SZXK06162) for supporting this research.
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Dedicated to Prof. Guoqiang Lin on the occasion of his 80th birthday

Abstract

Dihydropyrrolidone-thiadiazole inhibitors targeting YycG histidine kinase have been designed, synthesized and evaluated for their antibacterial, bactericidal, anti-biofilm, cytotoxic and hemolytic activities, and for their ability to promote autophosphorylation. 4-(Benzofuran-2-carbonyl)-1-(5-(benzylthio)-1,3,4-thiadiazol-2-yl)-3-hydroxy-5-(2-hydroxyphenyl)-1,5-dihydro-2H-pyrrol-2-one exhibits the best bacteriostatic activity against Gram-positive bacteria such as S. epidermidis SE1457, MSSA SA113, and E. faecalis FB1 (MIC = 3.13–25 μM). Its antibacterial activity against methicillin-sensitive Staphylococcus aureus (MSSA) SA113 is comparable to that of linezolid. Most of the products exhibit good inhibitory effects against the biofilms of the tested strains. Among the products, three show strong inhibitory effects on the biofilm formation of S. epidermidis SE1457, MSSA SA113, and E. faecalis FB1, and their inhibition rates reach more than 90% at 6.25 μM. Cytotoxicity and hemolytic activity tests suggest that all the synthesized compounds have little effect on the growth of mammalian cells (Vero cells) and exhibit no hemolytic activity toward healthy human red blood cells.

Key words

dihydropyrrolidone - 1,3,4-thiadiazole - derivatization - antibacterial - anti-biofilm

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2023-0028.
  • Supporting Information


Publication History

Received: 04 December 2022

Accepted after revision: 31 January 2023

Accepted Manuscript online:
31 January 2023

Article published online:
09 March 2023

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