Saldívar-González Fernanda I, Lenci Elena, Trabocchi Andrea, Medina-Franco José L
School of Chemistry, Department of Pharmacy, Universidad Nacional Autónoma de México Avenida Universidad 3000 Mexico City 04510 Mexico
Department of Chemistry "Ugo Schiff", University of Florence Via della Lastruccia 13 50019 Sesto Fiorentino Italy
RSC Adv. 2019 Aug 28;9(46):27105-27116. doi: 10.1039/c9ra04841c. eCollection 2019 Aug 23.
Lactams are a class of compounds important for drug design, due to their great variety of potential therapeutic applications, spanning cancer, diabetes, and infectious diseases. So far, the biological profile and chemical diversity of lactams have not been characterized in a systematic and detailed manner. In this work, we report the chemoinformatic analysis of beta-, gamma-, delta- and epsilon-lactams present in databases of approved drugs, natural products, and bioactive compounds from the large public database ChEMBL. We identified the main biological targets in which the lactams have been evaluated according to their chemical classification. We also identified the most frequent scaffolds and those that can be prioritized in chemical synthesis, since they are scaffolds with potential biological activity but with few reported analogs. Results of the biological and chemoinformatic analysis of lactams indicate that spiro- and bridged-lactams belong to classes with the lowest number of compounds and unique scaffolds, and some showing activity against specific targets. Information obtained from this analysis allows focusing the design of new chemical structures in less explored spaces and with increased possibilities of success.
内酰胺类是一类对药物设计很重要的化合物，因为它们具有各种各样潜在的治疗应用，涵盖癌症、糖尿病和传染病等领域。到目前为止，内酰胺类的生物学特性和化学多样性尚未得到系统而详细的表征。在这项工作中，我们报告了对来自大型公共数据库ChEMBL的已批准药物、天然产物和生物活性化合物数据库中存在的β-、γ-、δ-和ε-内酰胺进行的化学信息学分析。我们根据内酰胺类的化学分类确定了对其进行评估的主要生物学靶点。我们还确定了最常见的骨架以及那些在化学合成中可以优先考虑的骨架，因为它们是具有潜在生物活性但报道的类似物较少的骨架。内酰胺类的生物学和化学信息学分析结果表明，螺环和桥连内酰胺属于化合物数量最少且具有独特骨架的类别，其中一些对特定靶点具有活性。从该分析中获得的信息有助于在较少探索的领域聚焦新化学结构的设计，并增加成功的可能性。
