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Synthesis, biological evaluation, and computational investigation of ethyl 2,4,6-trisubstituted-1,4-dihydropyrimidine-5-carboxylates as potential larvicidal agents against Anopheles arabiensis
- Source :
- Journal of Biomolecular Structure and Dynamics; May 2024, Vol. 42 Issue: 8 p4016-4028, 13p
- Publication Year :
- 2024
-
Abstract
- AbstractMalaria is one of the most known vector-borne diseases caused by female Anophelesmosquito bites. According to WHO, about 247 million cases of malaria and 619,000 deaths were estimated worldwide in 2021, of which 95% of the cases and 96% of deaths occurred in the African region. Sadly, about 80% of all malaria deaths were of children under five years old. Despite the availability of different insecticides used to control this disease, the emergence of drug-resistant mosquitoes threatens public health. This, in turn, highlighted the need for new larvicidal agents that are effective at different larval life stages. This study aimed to identify novel larvicidal agents. To this end, a series of ethyl 2,4,6-trisubstituted-1,4-dihydropyrimidine-5-carboxylates 8a-iwas synthesized using a three-step chemical synthetic approach viaa Biginelli reaction employed as a key step. All title compounds were screened against Anopheles arabiensisto determine their larvicidal activities. Among them, two derivatives, ethyl 2-((4-bromophenyl)amino)-4-(4-fluorophenyl)-6-methyl-1,4-dihydropyrimidine-5-carboxylate 8band ethyl 2-((4-bromo-2-cyanophenyl)amino)-4-(4-fluorophenyl)-6-methyl-1,4-dihydropyrimidine-5-carboxylate 8f, showed the highest larvicidal activity, with mortality of 94% and 91%, respectively, and emerged as potential larvicidal agents. In addition, computational studies, including molecular docking and molecular dynamics simulations, were carried out to investigate their mechanism of action. The computational results showed that acetylcholinesterase appears to be a plausible molecular target for their larvicidal property.Communicated by Ramaswamy H. Sarma
Details
- Language :
- English
- ISSN :
- 07391102 and 15380254
- Volume :
- 42
- Issue :
- 8
- Database :
- Supplemental Index
- Journal :
- Journal of Biomolecular Structure and Dynamics
- Publication Type :
- Periodical
- Accession number :
- ejs66166141
- Full Text :
- https://doi.org/10.1080/07391102.2023.2217929