Volume 16, Issue 1: 2026 - Article 210

Abstract
Malaria remains a major global health challenge, which is compounded by the emergence of resistance to existing drugs such as chloroquine. To address this, the search for novel derivatives with improved therapeutic profile is ongoing. The present study designed, synthesized and characterized five novel chloroquine derivatives, and evaluated them for anti-malarial and anti-oxidant activities.  The synthesis began with the preparation of N1-(7-chloro-4-quinolyl)-1,2-diaminoethane via the reaction of 4,7-dichloroquinoline with ethylenediamine, affording an excellent yield. Subsequent condensation of this intermediate with various aromatic aldehydes produced the target imine derivatives in good yields. Structural elucidation was performed using ¹H NMR, ¹³C NMR, and mass spectrometry. In vitro anti-malarial activity was assessed in DMSO using chloroquine diphosphate as the positive control. Three of the compounds, N1-(7-chloro-4-quinolyl)-1,2-diaminoethane (Compound A), (E)-N-(2-(benzylideneamino)ethyl)-7-chloroquinolin-4-amine (Compound E), and N-(2-((7-chloroquinolin-4-yl)amino)ethyl)-4-nitrobenzamide (Compound C) displayed remarkable inhibitory effects, with IC₅₀ values of 0.015, 1.50, and 1.83 mg/ml, respectively, outperforming the standard chloroquine diphosphate (IC₅₀ = 2.50 mg/ml). Anti-oxidant activity was evaluated through free radical scavenging assays using DPPH. Compounds C and D, ((E)-2-(((2-((7-chloroquinolin-4-yl)amino)ethyl)imino) methyl)benzoic acid) showed potent anti-oxidant activity, with IC₅₀ values of 0.57 and 0.64 mg/ml, respectively, surpassing the standard ascorbic acid (IC₅₀ = 1.53 mg/ml). It was concluded that the synthesized chloroquine derivatives, particularly Compounds A, C, D and E, demonstrated in vitro anti-malarial and/or anti-oxidant activities compared to established standards. These findings suggest that structural modification of chloroquine can yield promising lead candidates for further development of treatment drugs for malaria and oxidative stress-related conditions.


Keywords: Chloroquine derivatives; Synthesis; In vitro evaluation; Anti-malarial; Anti-oxidant activity.

How to cite this article:
Attah SI, Ezugwu JC, Onoabedje EA, Ezema BE, Madubuchi FC, Eze CC, Okonkwo IV, Ibeanu FN and Onyejekwe BO (2025). Synthesis of chloroquine derivatives and their in vitro screening for anti-malarial and anti-oxidant activity. Journal of Veterinary and Applied Sciences, 16(1): 1269 – 1278.


*Correspondence: E-mail:     solomom.attah@unn.edu.ng     Phone: +23408063660524

Synthesis of chloroquine derivatives and their in vitro screening for anti-malarial and anti-oxidant activity
Solomon I. Attah ¹ *, Joy C. Ezugwu ¹, Efeturi A. Onoabedje ¹, Benjamin E. Ezema ¹, Festus C. Madubuchi ¹, Cosmas C. Eze ², Ifeoma V. Okonkwo ³, Fidelia N. Ibeanu ² and Benedict O. Onyejekwe <sup>4

1</sup> Department of Pure and Industrial Chemistry, Faculty of Physical Sciences, University of Nigeria, Nsukka, Enugu State, Nigeria.
² School of General Studies, Natural Science Unit, University of Nigeria, Nsukka, Enugu State, Nigeria
³ Department of Science Laboratory Technology, Faculty of  Physical Sciences, University of Nigeria, Nsukka, Enugu State, Nigeria.
⁴ Department of Veterinary Physiology and Biochemistry, Faculty of Veterinary Medicine, University of Nigeria, Nsukka, Enugu State, Nigeria.

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