Development and Validation of a Liquid Chromatography-Tandem Mass Spectrometry Method for Screening Potential Citrate Lyase Inhibitors from a Library of Marine Compounds.

Wang, Jiahong; Guan, Huashi; Xu, Zhe

Wang, Jiahong; Guan, Huashi; Xu, Zhe.

Afiliación

Wang J; Key Laboratory of Marine Drugs, Chinese Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycoengineering, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
Guan H; Laboratory for Marine Drugs and Bioproducts, Innovation Center for Marine Drugs Screening and Evaluation, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China.
Xu Z; Key Laboratory of Marine Drugs, Chinese Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycoengineering, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.

Mar Drugs ; 22(6)2024 May 27.

Article en En | MEDLINE | ID: mdl-38921556

ABSTRACT

ABSTRACT

Tuberculosis, a persistent illness caused by Mycobacterium tuberculosis, remains a significant global public health challenge. The widespread use of anti-tuberculosis drugs has resulted in the emergence of drug-resistant strains, which complicates treatment efforts. Addressing this issue is crucial and hinges on the development of new drugs that can effectively target the disease. This involves identifying novel therapeutic targets that can disrupt the bacterium's survival mechanisms in various environments such as granulomas and lesions. Citrate lyase, essential for the survival of Mycobacterium species at lesion sites and in granulomatous conditions, is a potential target for the treatment of tuberculosis. This manuscript aimed to construct an efficient enzyme inhibitor screening platform using ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF MS). This system can accurately identify compounds with enzyme inhibitory activity from a library of marine terpenoids and phenolic compounds. Utilizing the screened herbal enzyme inhibitors as a starting point, we analyzed their chemical structures and skillfully built a library of marine compounds based on these structures. The results showed that all of the tested compounds from the phenolics library inhibited citrate lyase by more than 50%, and a significant portion of terpenoids also demonstrated inhibition, with these active terpenoids comprising over half of the terpenoids tested. The study underscores the potential of marine-derived phenolic and terpenoid compounds as potent inhibitors of citrate lyase, indicating a promising direction for future investigations in treating tuberculosis and associated disorders.

Asunto(s)

Antituberculosos; Inhibidores Enzimáticos; Mycobacterium tuberculosis; Espectrometría de Masas en Tándem; Espectrometría de Masas en Tándem/métodos; Inhibidores Enzimáticos/farmacología; Inhibidores Enzimáticos/química; Antituberculosos/farmacología; Antituberculosos/química; Mycobacterium tuberculosis/efectos de los fármacos; Mycobacterium tuberculosis/enzimología; Cromatografía Líquida de Alta Presión/métodos; ATP Citrato (pro-S)-Liasa/antagonistas & inhibidores; Organismos Acuáticos; Terpenos/farmacología; Terpenos/química; Humanos; Fenoles/farmacología; Fenoles/química; Cromatografía Liquida/métodos

Palabras clave

UHPLC-QTOF MS; citrate lyase inhibitors; phenolic compounds; terpenoids compounds; tuberculosis

Texto completo

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores Enzimáticos / Espectrometría de Masas en Tándem / Mycobacterium tuberculosis / Antituberculosos Límite: Humans Idioma: En Revista: Mar Drugs Asunto de la revista: BIOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza

Texto completo

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Buscar en Google