Conjugation of N-acylhydrazone and 1,2,4-oxadiazole leads to the identification of active antimalarial agents |
| |
| Affiliation: | 1. Laboratory of Design and Synthesis Applied to Medicinal Chemistry-SintMed®, Centro de Tecnologia e Geociências, Universidade Federal de Pernambuco, CEP 50740-521 Recife, PE, Brazil;2. Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, CEP 40296-710 Salvador, BA, Brazil;3. School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, 30 quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland;4. Centro de Biotecnologia e Terapia Celular, Hospital São Rafael, CEP 41253-190 Salvador, BA, Brazil;1. Departamento de Química, Universidade Estadual de Maringá (UEM), 87020-900, Maringá, PR, Brazil;2. Programa de Pós-Graduação em Ciências Biológicas, Universidade Estadual de Maringá (UEM), 87020-900, Maringá, PR, Brazil;3. Departamento de Farmácia, Universidade Federal do Pampa (UNIPAMPA), 97500-970, Uruguaiana, RS, Brazil;1. Huangshi Central Hospital, Hubei Polytechnic University, Huangshi 435000, People’s Republic of China;2. National Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan 430064, People’s Republic of China;1. Department of Chemistry, College of Sciences, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia;2. Biomolecular Crystallography Laboratory, Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur 613 401, India;3. Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt;4. Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur 613 401, India;5. Department of Pharmaceutical Chemistry, College of Pharmacy, Sattam Bin Abdulaziz University, Alkharj 11942, Saudi Arabia;6. Unidad de Polímeros y Electrónica Orgánica, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Val3-Ecocampus Valsequillo, Independencia O2 Sur 50, San Pedro Zacachimalpa, Pue. Mexico |
| |
| Abstract: | Malaria, caused by several Plasmodium species, is the major life-threatening parasitic infection worldwide. Due to the parasite resistance to quinoline based drugs, the search for antimalarial agents is necessary. Here, we report the structural design, synthesis and antiparasitic evaluation of two novel series of 1,2,4-oxadiazoles in conjugation to N-acylhydrazones, both groups recognized as privileged structures, as well as the studies on the antimalarial activity of 16 previous described analogues. By varying substituents attached to the phenyl ring, it was possible to retain, enhance or increase the antiparasitic activity in comparison to the nonsubstituted derivatives. Replacement of substituted aryl rings by ferrocenyl and cinnamyl moieties attached in the N-acylhydrazone ablated the antiparasitic response, evidencing the structural features associated with the activity. Active compounds exhibited in vitro potency similar to mefloquine, but not all inhibited β-hematin formation. Additionally, the active compounds displayed low cytotoxicity in HepG2 cells and did not cause hemolysis in uninfected erythrocytes. In Plasmodium berghei-infected mice, the compounds reduced parasitemia but exhibited limited efficacy in increasing mice survival when compared to chloroquine, suggesting that pharmacological improvement is still necessary. |
| |
| Keywords: | Malaria Drug design 1,2,4-Oxadiazoles |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
