Insights into the In-vivo Antiplasmodial Activity of Trisdimethylamino Pyrimidine Derivative in Plasmodium berghei: Infected Mouse Model
Chibuike Ernest Ikwuka
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka - 410001, Enugu State, Nigeria.
Chukwuebuka Moses Asogwa
Department of Pharmaceutical Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka – 410001, Enugu State, Nigeria.
Ozioma Jennifer Ikwuka
Department of Pure and Industrial Chemistry, Faculty of Physical Sciences, Chukwuemeka Odumegwu Ojukwu University (Formerly Anambra State University), Uli, Anambra State, Nigeria.
Jude Ebuka Ogbonna
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka - 410001, Enugu State, Nigeria.
Chinwe Mercy Onah
Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka – 410001, Enugu State, Nigeria.
Christian Chukwuagozie Ohama
Department of Pharmacognosy and Environmental Medicines, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka – 410001, Enugu State, Nigeria.
Charles Okeke Nnadi *
Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka – 410001, Enugu State, Nigeria.
*Author to whom correspondence should be addressed.
Abstract
Aims: To evaluate the antiplasmodial activity of a trisdimethylamino pyrimidine derivative synthesized by indirect methylation of p-nitrophenylacetic acid via a substituted amine or amide derivative against Plasmodium berghei NK65 strain in an in vivo Plasmodium berghei-Infected mouse model.
Methodology: Plasmodium berghei-parasitized suppressive model in Albino mice was adopted for the antiplasmodial activity evaluation. The schizontocidal activity of the compound was evaluated by a 4-day suppressive test. All the treatments (test sample, standard control and blank) were administered intraperitoneally to the mice. Parameters such as rectal temperature, packed cell volume, survival time and parasitemia were measured.
Results: The 10, 20 and 40 mg/kg doses of 2, 4, 6-trisdimethylamino-5-(4´-nitrophenyl) pyrimidine elicited a statistically significant reduction (p < 0.01) in parasitemia level in treated mice. The 40 mg/kg dose caused 97.19% suppression of parasitemia and a mean survival time of 22 days compared with 97.64% and 24 days respectively in the standard control group (artemether-lumefantrine combination, 5 mg/kg). All the treatments restored the packed cell volume to the baseline (~39.8%). A dose-dependent decrease in the rectal temperature was observed in all the treatment groups. However, only the 10 and 20 mg/kg doses of 2, 4, 6-trisdimethylamino-5-(4´-nitrophenyl) pyrimidine caused a significant decrease (p < 0.01) compared with the control.
Conclusion: The strong suppression of Plasmodium berghei in the mice treated with 2, 4, 6-trisdimethylamino-5-(4´-nitrophenyl) pyrimidine has further provided insights into the potential of the compound as a lead in the discovery of antimalarial agents.
Keywords: Antimalaria, infected mouse model, Plasmodium berghei, pyrimidine derivative, vilsmeier-haack reaction