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6-1,2-恶嗪-6-酮的设计、合成及抗菌活性研究

Design, synthesis, and exploration of antibacterial activity of 6-1,2-oxazin-6-ones.

作者信息

Alcántar-Zavala Eleazar, Delgado-Vargas Francisco, Marín-González Fabricio, Angulo Gabriela López, Aguirre-Madrigal Hugo Enrique, Ochoa-Terán Adrián, Rodríguez-Vega Gibrán, Aguirre-Hernández Gerardo, Montes-Avila Julio

机构信息

Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Sinaloa Culiacán 80010 Sinaloa Mexico.

Programa de Posgrado en Ciencias Biomédicas, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Sinaloa Culiacán 80010 Sinaloa Mexico

出版信息

RSC Adv. 2024 Jul 29;14(33):23828-23839. doi: 10.1039/d4ra04220d. eCollection 2024 Jul 26.

DOI:10.1039/d4ra04220d
PMID:39077316
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11285021/
Abstract

This study reports the design of 30 6-1,2-oxazin-6-ones against DHFR and PTC antimicrobial targets. Docking compounds 1, 3, 4, 6, and 8 with both enzymes was favorable, outperforming Trimethoprim with DHFR. Therefore, 12 6-1,2-oxazin-6-ones, including the most promising compounds, were synthesized through an aminolysis reaction of β-cyanoketones with hydroxylamine hydrochloride, obtaining moderate to high yields (55-88%). Subsequently, antibacterial studies were conducted against five bacteria: four Gram-positive MRSA (ATCC 43300 and three clinical isolates) and one Gram-negative ( ATCC 25922). Compounds 1, 2, 3, 4, 6, and 8 inhibited bacterial growth with MIC values ranging from 3.125 to 200 μg mL. Compound 1 showed better activity against Gram-positive bacteria than Linezolid. Toxicity assays indicated no adverse effects of the active oxazinones and . This study demonstrated the antibacterial potential of the selected 6-1,2-oxazin-6-ones against resistant human pathogenic bacteria.

摘要

本研究报告了针对二氢叶酸还原酶（DHFR）和肽基转移酶中心（PTC）抗菌靶点设计的30种6-1,2-恶嗪-6-酮。化合物1、3、4、6和8与这两种酶的对接效果良好，优于甲氧苄啶与DHFR的对接效果。因此，通过β-氰基酮与盐酸羟胺的氨解反应合成了12种6-1,2-恶嗪-6-酮，包括最有前景的化合物，产率适中至较高（55-88%）。随后，对五种细菌进行了抗菌研究：四种革兰氏阳性耐甲氧西林金黄色葡萄球菌（ATCC 43300和三株临床分离株）和一种革兰氏阴性菌（ATCC 25922）。化合物1、2、3、4、6和8抑制细菌生长，最低抑菌浓度（MIC）值范围为3.125至200μg/mL。化合物1对革兰氏阳性菌的活性优于利奈唑胺。毒性试验表明活性恶嗪酮没有不良反应。本研究证明了所选6-1,2-恶嗪-6-酮对耐药人类病原菌的抗菌潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d04/11285021/b41d2afb2494/d4ra04220d-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d04/11285021/5a4c10c779e1/d4ra04220d-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d04/11285021/7e6f7a0f22e2/d4ra04220d-s1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d04/11285021/371838e0c828/d4ra04220d-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d04/11285021/aa718d17a02a/d4ra04220d-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d04/11285021/51ebaebd755f/d4ra04220d-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d04/11285021/b41d2afb2494/d4ra04220d-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d04/11285021/5a4c10c779e1/d4ra04220d-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d04/11285021/7e6f7a0f22e2/d4ra04220d-s1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d04/11285021/371838e0c828/d4ra04220d-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d04/11285021/aa718d17a02a/d4ra04220d-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d04/11285021/51ebaebd755f/d4ra04220d-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d04/11285021/b41d2afb2494/d4ra04220d-f5.jpg

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