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  3. Design and synthesis of unique indole-benzosulfonamide oleanolic acid derivatives as potent antibacterial agents against MRSA

Design and synthesis of unique indole-benzosulfonamide oleanolic acid derivatives as potent antibacterial agents against MRSA

  • Eur J Med Chem. 2024 Jun 27:276:116625. doi: 10.1016/j.ejmech.2024.116625.
Jinxuan Li 1,  Ying Sun 1,  Kaize Su 1,  Xu Wang 1,  Duanyu Deng 1,  Xiaofang Li 1,  Lihua Liang 1,  Wenhuan Huang 1,  Xiangcun Shang 1,  Yan Wang 1,  Zhen Zhang 1,  Song Ang 1,  Wing-Leung Wong 2,  Panpan Wu 3,  Weiqian David Hong 4
Affiliations

Affiliations

  • 1 School of Pharmacy and Food Engineering, Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, Wuyi University, Jiangmen, 529020, China.
  • 2 The State Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China.
  • 3 School of Pharmacy and Food Engineering, Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, Wuyi University, Jiangmen, 529020, China. Electronic address: wyuchemwpp@wyu.edu.cn.
  • 4 Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK. Electronic address: davidhwq@liverpool.ac.uk.
PMID: 38991300 DOI: 10.1016/j.ejmech.2024.116625
Abstract

The rapid emergence of Antibiotic resistance and the scarcity of novel Antibacterial agents have necessitated an urgent pursuit for the discovery and development of novel Antibacterial agents against multidrug-resistant bacteria. This study involved the design and synthesis of series of novel indole-benzosulfonamide oleanolic acid (OA) derivatives, in which the indole and benzosulfonamide pharmacophores were introduced into the OA skeleton semisynthetically. These target OA derivatives show Antibacterial activity against Staphylococcus strains in vitro and in vivo. Among them, derivative c17 was the most promising Antibacterial agent while compared with the positive control of norfloxacin, especially against methicillin-resistant Staphylococcus aureus (MRSA) in vitro. In addition, derivative c17 also showed remarkable efficacy against MRSA-infected murine skin model, leading to a significant reduction of Bacterial counts during this in vivo study. Furthermore, some preliminary studies indicated that derivative c17 could effectively inhibit and eradicate the biofilm formation, disrupt the integrity of the Bacterial cell membrane. Moreover, derivative c17 showed low hemolytic activity and low toxicity to mammalian cells of NIH 3T3 and HEK 293T. These aforementioned findings strongly support the potential of novel indole-benzosulfonamide OA derivatives as anti-MRSA agents.

Keywords

Anti-MRSA; Indole-benzosulfonamide; Oleanolic acid derivatives; Synthesis.

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