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黄酮类和嘧啶类化合物的抗分枝杆菌活性。

Anti-Mycobacterial Activity of Flavonoid and Pyrimidine Compounds.

机构信息

Department of Surgery, Ray Rajotte Surgical-Medical Research Institute, Alberta Diabetes, and Transplant Institutes, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 0X0, Canada.

ImMed Biotechnologies, Edmonton, AB T6R 2E8, Canada.

出版信息

Molecules. 2022 Oct 9;27(19):6714. doi: 10.3390/molecules27196714.

Abstract

We evaluated the anti-mycobacterial effect of a flavonoid 5,7-dihydroxy-2-(4-hydroxyphenyl) 4-chromen-4-one () and two pyrimidines, 4-hydroxy-2-dimethylamino-5-nitroso-6-aminopyrimidine () and 2-chloro-5--nonylpyrimidine () in vitro against (, H37Ra) and , using a Microplate Alamar Blue Assay (MABA). The effects of the compounds - in combination with first- and second-line anti-TB drugs isoniazid, rifampicin, cycloserine, and clarithromycin on the growth of and were also evaluated in in vitro assays. As a single agent, compounds and exhibited modest activity while compound was the most effective against and . When compounds - were evaluated at lower than 50% of their inhibitory concentrations in a two-drug combination with isoniazid or rifampicin, they showed additive to synergistic interactions. This inhibitory effect was improved when each of the three compounds was tested together in a three-drug combination with two of the first-line anti-TB drugs. Compounds - also demonstrated strong synergistic interaction in combination with cycloserine and clarithromycin in inhibiting the growth of and , respectively. This study demonstrated that compounds - have potential to be developed as effective anti-TB agents with combined use.

摘要

我们评估了一种黄酮类化合物 5,7-二羟基-2-(4-羟基苯基)-4-色烯-4-酮()和两种嘧啶类化合物 4-羟基-2-二甲基氨基-5-亚硝基-6-氨基嘧啶()和 2-氯-5--壬基嘧啶()对结核分枝杆菌(,H37Ra)和结核分枝杆菌的体外抗微生物作用,采用微量板 Alamar Blue 测定法(MABA)。还评估了化合物 - 与一线和二线抗结核药物异烟肼、利福平、环丝氨酸和克拉霉素联合对 和 生长的影响。作为单一药物,化合物 和 表现出适度的活性,而化合物 对 和 最有效。当化合物 - 在低于其与异烟肼或利福平联合使用时的抑制浓度的 50%以下进行评估时,它们显示出相加到协同相互作用。当这三种化合物中的每一种与两种一线抗结核药物联合在三药组合中进行测试时,这种抑制作用得到了改善。化合物 - 与环丝氨酸和克拉霉素联合使用时,对 和 的生长也表现出很强的协同相互作用。这项研究表明,化合物 - 具有联合使用开发为有效抗结核药物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f77/9572476/5d1c2b0b64b1/molecules-27-06714-g001.jpg

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