Bioisosteric replacements are often tried goaling to affect the lipophilicity, polarity, and aqueous solubility of the substances, as a way to obtain therapeutically improved medicines. Also, hydrazonyl compounds are described with a wide range of pharmacological activities, having also recognized activities in antimycobacterial field. In this study, twenty-seven pyrimidinyl and pyrazinyl derivatives have been synthesized and evaluated for their antimycobacterial activity against M. tuberculosis ATTC 27294. The componds were obtained by the reaction of 2-hydrazinylpyridine, 4-hydrazinylpyridine, or 2-hydrazinylpyrazine with appropriated aromatic or heteroaromatic aldehydes. Antimycobacterial activity of the compounds was determined according to MTT assay. The most active compound, a 2-hydroxyl-5-nitrophenyl-4-pyridinylhydrazone derivative, showed good biodisponibility and nonmutagenic or tumorigenic profiles in preliminaries in silico studies, and exceptional in vitro activity, being compared with the reference drug ethambutol. This study supports that pyrimidinyl and pyrazinyl derivatives may be used for the development of new tuberculostatic agents.

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吡啶基和吡嗪基yl衍生物的合成和抗分枝杆菌作用

经常尝试生物等位替代物，以影响该物质的亲脂性，极性和水溶性，以此作为获得治疗上改善的药物的途径。此外，描述了具有广泛药理活性的肼基化合物，其在抗分枝杆菌领域也具有公认的活性。在这项研究中，已合成了27个嘧啶基和吡嗪基衍生物，并评估了它们对结核分枝杆菌的抗分枝杆菌活性。ATTC 27294.该化合物是通过2-羟基苯并吡啶，4-羟基苯并吡啶或2-羟基苯并吡嗪与适当的芳族或杂芳族醛反应而获得的。根据MTT测定法测定化合物的抗分枝杆菌活性。与参考药物乙胺丁醇相比，最活跃的化合物2-羟基5-硝基苯基-4-吡啶基hydr衍生物在计算机模拟研究的初步研究中显示出良好的生物适应性和非诱变或致瘤性，并具有出色的体外活性。这项研究支持嘧啶基和吡嗪基衍生物可用于开发新型抗结核药。