Gini Ana Luísa Rodriguez, Emilio João Emilio, Dos Santos Jean Leandro, Scarim Cauê Benito
Department of Drugs and Medicines, School of Pharmaceutical Sciences, Sao Paulo State University (UNESP), Araraquara, SP, Brazil.
Curr Med Chem. 2025 Mar 10. doi: 10.2174/0109298673360057250219044138.
Mannich bases, synthesized through the reaction of an aldehyde, a primary or secondary amine, and a compound bearing an acidic hydrogen atom, represent a versatile class of scaffolds in medicinal chemistry. This review explores their broad spectrum of biological activities, emphasizing their potential in combating infectious diseases. With demonstrated efficacy against bacteria, fungi, and parasites, Mannich bases stand out as promising candidates for the development of novel therapeutic agents. Their versatility arises from the ability of their electronic, steric, and conformational parameters to modulate receptor interactions, significantly expanding their applicability in drug design. The review provides an in-depth analysis of the structure-activity relationship (SAR) of Mannich bases, highlighting how specific structural modifications enhance their biological activity. Additionally, it examines the lipophilic properties of these compounds, offering key insights into their influence on pharmacokinetics and pharmacodynamics. This understanding is essential for optimizing the development of novel therapeutics, particularly for addressing challenging infectious diseases. By integrating these aspects, this review underscores the pivotal role of Mannich bases in overcoming current challenges in drug resistance and shaping the future of drug discovery and development.
通过醛、伯胺或仲胺与带有酸性氢原子的化合物反应合成的曼尼希碱，是药物化学中一类用途广泛的骨架结构。本综述探讨了它们广泛的生物活性，强调了它们在对抗传染病方面的潜力。曼尼希碱已证明对细菌、真菌和寄生虫有效，是开发新型治疗药物的有前途的候选物。它们的多功能性源于其电子、空间和构象参数调节受体相互作用的能力，显著扩大了它们在药物设计中的适用性。该综述对曼尼希碱的构效关系（SAR）进行了深入分析，突出了特定结构修饰如何增强其生物活性。此外，它还研究了这些化合物的亲脂性，提供了关于它们对药代动力学和药效学影响的关键见解。这种理解对于优化新型治疗药物的开发至关重要，特别是对于应对具有挑战性的传染病。通过整合这些方面，本综述强调了曼尼希碱在克服当前耐药性挑战以及塑造药物发现和开发未来方面的关键作用。
