Charles University, Faculty of Pharmacy in Hradec Králové, Akademika Heyrovského 1203, Hradec Králové, Czech Republic.
University Hospital Hradec Králové, Department of Clinical Microbiology, Sokolská 581, 500 05 Hradec Králové, Czech Republic.
Molecules. 2020 Mar 27;25(7):1518. doi: 10.3390/molecules25071518.
Tuberculosis is an infectious disease caused by (Mtb), each year causing millions of deaths. In this article, we present the synthesis and biological evaluations of new potential antimycobacterial compounds containing a fragment of the first-line antitubercular drug pyrazinamide (PZA), coupled with methyl or ethyl esters of selected amino acids. The antimicrobial activity was evaluated on a variety of (myco)bacterial strains, including Mtb H37Ra, and fungal strains, including and . Emphasis was placed on the comparison of enantiomer activities. None of the synthesized compounds showed any significant activity against fungal strains, and their antibacterial activities were also low, the best minimum inhibitory concentration (MIC) value was 31.25 µM. However, several compounds presented high activity against Mtb. Overall, higher activity was seen in derivatives containing ʟ-amino acids. Similarly, the activity seems tied to the more lipophilic compounds. The most active derivative contained phenylglycine moiety (PC-ᴅ/ʟ-Pgl-Me, MIC < 1.95 µg/mL). All active compounds possessed low cytotoxicity and good selectivity towards Mtb. To the best of our knowledge, this is the first study comparing the activities of the ᴅ- and ʟ-amino acid derivatives of pyrazinamide as potential antimycobacterial compounds.
结核病是一种由结核分枝杆菌（Mtb）引起的传染病，每年导致数百万人死亡。在本文中，我们合成并评估了一些新的潜在抗分枝杆菌化合物，这些化合物含有一线抗结核药物吡嗪酰胺（PZA）的片段，并与选定氨基酸的甲酯或乙酯相连。我们评估了这些化合物对各种（分枝杆菌）细菌株，包括结核分枝杆菌 H37Ra，以及真菌株，包括 和 的抗菌活性。重点比较了对映异构体的活性。所合成的化合物均对真菌株没有显示出任何显著的活性，其抗菌活性也较低，最佳最小抑菌浓度（MIC）值为 31.25 µM。然而，有几种化合物对结核分枝杆菌表现出很高的活性。总体而言，含 L-氨基酸的衍生物表现出更高的活性。同样，活性似乎与更亲脂性的化合物有关。最活跃的衍生物含有苯甘氨酸部分（PC-ᴅ/ʟ-Pgl-Me，MIC < 1.95 µg/mL）。所有活性化合物均具有低细胞毒性和对结核分枝杆菌的良好选择性。据我们所知，这是首次比较吡嗪酰胺的 D-和 L-氨基酸衍生物作为潜在抗分枝杆菌化合物的活性的研究。
