New isoleucine derived dipeptides as antiprotozoal agent: Synthesis, in silico and in vivo studies

• Published in: Journal of molecular structure 2021-05, Vol.1231, p.130017, Article 130017
• Main Authors: Ekoh, Ogechi C., Okoro, Uchechukwu C., Ali, Rafat, Ugwu, David I., Okafor, Sunday N., Ezugwu, James A.
• Format: Article
• Language: English
• Subjects: Antimalaria; Antitrypanosomal; Dipeptide; Isoleucine; Molecular docking; Sulphonamide
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2021.130017

•In the tropical regions of the world, protozoan parasites cause severe diseases.•Malaria and human african trypanosomaisis (HAT) stand in forefront.•There are problems of parasite resistance to drugs and current inadequate chemotherapy for these diseases.•Result of this research shows interesting antimalaria and antitrypanosomaisis activities.•Molecular docking result showed good interaction between the compounds and proteins. The increasing emergence of malaria drug-resistant parasites and the deficiency in effective chemotherapy for trypanosomiasis represents a huge challenge in infectious disease treatment in tropical regions. As regards to developing effective antiprotozoal agents, ten new ile-gly dipeptide sulphonamide derivatives were synthesized by condensing compound (10) with (8a-j)using peptide coupling reagents. Compounds11b, 11i and 11j were most potent in clearing Trypanosome brucei in mice with 11b showing comparable activity with diminazene aceturate. In the antimalarial study, 11b was the most active compound, even better than the standard. Molecular docking result suggests good interaction between the reported compounds and the target protein. The results of haematological analysis, liver and kidney function tests showed that the compounds had no adverse effect on the blood and organs. Compound 11b stands out amongst the derivatives haven shown better activity in both the antimalarial and antitrypanosomal assay.