Discovery of novel phenylhydrazone-based oxindole-thiolazoles as potent antibacterial agents toward Pseudomonas aeruginosa.

Autor: Li FF; Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, China., Zhao WH; Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, China., Tangadanchu VKR; Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, China., Meng JP; College of Pharmacy, National & Local Joint Engineering Research Center of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators As Innovative Medicine, Chongqing University of Arts and Sciences, Chongqing, 402160, China. Electronic address: mengjp2006@163.com., Zhou CH; Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, China. Electronic address: zhouch@swu.edu.cn.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2022 Sep 05; Vol. 239, pp. 114521. Date of Electronic Publication: 2022 Jun 09.
DOI: 10.1016/j.ejmech.2022.114521
Abstrakt: With the soaring of bacterial infection and drug resistance, it is imperative to exploit new efficient antibacterial agents. This work constructed a series of unique phenylhydrazone-based oxindole-thiolazoles to combat monstrous bacterial resistance. Some target molecules showed potent antibacterial activity, among which oxindole-thiolimidazole derived carboxyphenylhydrazone 4e exhibited an 8-fold stronger inhibitory ability than norfloxacin on the growth of P. aeruginosa, with MIC value of 1 μg/mL. Compound 4e with imperceptible hemolysis could hamper bacterial biofilm formation and significantly impede the development of bacterial resistance. Subsequent mechanism studies demonstrated that 4e could destruct bacterial cytoplasmic membrane, causing the leakage of cellular contents (protein and nucleic acid). Moreover, metabolic stagnation and intracellular oxidative stress caused by 4e expedited the death of bacteria. Furthermore, molecule 4e existed supramolecular interactions with DNA to block DNA proliferation. These research results provided a promising light for phenylhydrazone-based oxindole-thiolazoles as novel potential antibacterial agents.
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Databáze: MEDLINE
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