Laboratório de Síntese de Moléculas Medicinais (LaSMMed), Departamento de Química, Centro de Ciências Exatas, Universidade Estadual de Londrina, Londrina, Brazil.
Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Mini Rev Med Chem. 2023;23(14):1414-1434. doi: 10.2174/1389557523666230127125058.
Leishmaniases are infectious diseases caused by flagellated protozoan parasites belonging to the genus that infect cells of the mononuclear phagocytic system. These parasites are transmitted to humans by biting an infected female sandfly belonging to the genera in the Old World and in the New World. Despite representing a major public health problem, the therapeutic options are old and have several disadvantages. Given this scenario, developing vaccines or drugs for oral administration is necessary. Therefore, integrating computational and experimental strategies into the studies on molecular targets essential for the survival and virulence of the parasite is fundamental in researching and developing new treatments for leishmaniasis. In the effort to develop new vaccines and drugs, molecular docking methods are widely used as they explore the adopted conformations of small molecules within the binding sites of macromolecular targets and estimate the free energy of target-ligand binding. Privileged structures have been widely used as an effective model in medicinal chemistry for drug discovery. Chalcones are a common simple scaffold found in many compounds of natural and synthetic origin, where studies demonstrate the great pharmacological potential in treating leishmaniasis. This review is based on scientific articles published in the last ten years on molecular docking of chalcone derivatives for essential molecular targets of . Thus, this review emphasizes how versatile chalcone derivatives can be used in developing new inhibitors of important molecular targets involved in the survival, growth, cell differentiation, and infectivity of the parasites that cause leishmaniasis.
利什曼病是一种由鞭毛原生动物寄生虫引起的传染病，属于 属，感染单核吞噬细胞系统的细胞。这些寄生虫通过叮咬旧世界的感染雌性沙蝇（属于 属）和新世界的 属传播给人类。尽管利什曼病是一个重大的公共卫生问题，但治疗选择还是很陈旧，存在许多缺点。鉴于这种情况，开发用于口服的疫苗或药物是必要的。因此，将计算和实验策略整合到对寄生虫生存和毒力至关重要的分子靶标研究中，对于研究和开发利什曼病的新治疗方法至关重要。在开发新疫苗和药物的努力中，分子对接方法被广泛应用，因为它们可以探索小分子在大分子靶标结合位点中的采用构象，并估计靶标-配体结合的自由能。优势结构已被广泛用作药物化学中用于药物发现的有效模型。查耳酮是许多天然和合成来源的化合物中常见的简单支架，研究表明其在治疗利什曼病方面具有巨大的药理学潜力。这篇综述基于过去十年中关于查尔酮衍生物对 属的重要分子靶标的分子对接的科学文章。因此，本综述强调了查尔酮衍生物在开发新的抑制剂方面的多功能性，这些抑制剂涉及参与寄生虫生存、生长、细胞分化和感染的重要分子靶标，这些寄生虫会导致利什曼病。
