Pérez-Villanueva Jaime, Yépez-Mulia Lilián, Rodríguez-Villar Karen, Cortés-Benítez Francisco, Palacios-Espinosa Juan Francisco, Soria-Arteche Olivia
Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de La Salud, Universidad Autónoma Metropolitana-Xochimilco (UAM-X), Ciudad de México, 04960, Mexico.
Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, UMAE Hospital de Pediatría, Centro Médico Siglo XXI, Instituto Mexicano Del Seguro Social, Ciudad de México, 06720, Mexico.
Eur J Med Chem. 2021 Feb 5;211:113110. doi: 10.1016/j.ejmech.2020.113110. Epub 2020 Dec 17.
A ligand-based virtual screening study to search for giardicidal compounds on a 6551 ChEMBL drugs database was carried out using molecular similarity. Three fingerprints implemented in MayaChemTools with different design and validated by ROC curves, were used. Twelve compounds were retrieved from this screening, from which, four representative compounds were selected to carry out biological assays. Whereas two compounds were commercially available, the additional two compounds were synthesized during the development of this work. The biological assays revealed that the compounds possess in vitro activity against five strains of Giardia intestinalis, each with different susceptibility/resistance rates to metronidazole, albendazole and nitazoxanide. Particularly, tenatoprazole showed the best effect against the WB and IMSS strains. Furthermore, fabomotizole, tenatoprazole and ipriflavone showed a higher activity against resistant strains than the reference drugs: metronidazole, albendazole and nitazoxanide.
利用分子相似性，在一个包含6551种ChEMBL药物的数据库上开展了一项基于配体的虚拟筛选研究，以寻找杀贾第虫化合物。使用了在MayaChemTools中实现的具有不同设计并经ROC曲线验证的三种指纹图谱。通过此次筛选检索出12种化合物，从中选择了4种代表性化合物进行生物学测定。其中两种化合物有商业供应，另外两种化合物是在本研究开展过程中合成的。生物学测定表明，这些化合物对五株肠道贾第虫均具有体外活性，每株对甲硝唑、阿苯达唑和硝唑尼特的敏感/耐药率不同。特别是，雷贝拉唑对WB和IMSS菌株显示出最佳效果。此外，法莫替唑、雷贝拉唑和依普黄酮对耐药菌株的活性高于参考药物甲硝唑、阿苯达唑和硝唑尼特。
