New Quinolinyl Chalcones with Potential Antiplasmodial Activity: Synthesis and In Vivo Studies On Plasmodium Berghi

Document Type : Original research articles

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Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sceinces, Ahmadu Bello University, Zaria, Nigeria

Abstract

Malaria remains a devastating parasitic disease of the tropics, with reported decreased sensitivity to all the available drugs. Spurred by the previous literature and computational studies against four plasmodium proteases, three quinolinyl chalcone derivatives; 3-(2-chloro-6-methoxyquinolin-3-yl)-1-(2, 4-dimethoxyphenyl) prop-2-en-1-one (P3), 3-(2-chloroquinolin-3-yl)-1-(2, 4-dimethoxyphenyl) prop-2-en-1-one (P4) and 3-(2-chloro-6-methoxyquinolin-3-yl)-1-(2, 3, 4-trimethoxyphenyl) prop-2-en-1-one (P5) were synthesized and evaluated for their in vivo antiplasmodial activity. The synthesis was achieved through the Claisen–Schmidt condensation reaction of polymethoxylated acetophenones and substituted 3-quinolinyl carbaldehydes. The structures of these compounds were resolved using Fourier transform infrared (FT-IR), Proton, Carbon-13 and, two-dimensional nuclear magnetic resonance (NMR) spectroscopy in addition to, mass spectrometry (MS). In vivo antiplasmodial activity in mice infected with Plasmodium berghei parasite, was evaluated using a curative model. One-way analysis of variance (ANOVA) and Bonferroni post-hoc test was used to determine the statistical significance compared to the control.
Findings revealed that P5 showed significant (p < 0.001) dose-dependent chemo suppressive activity of 59.09, 70.36 and 77.6% at doses of 25, 50 and 100 mg kg-1 respectively, in comparison to 10 mg kg-1 quinine (88.5%) and 25 mg kg-1 chloroquine (85.5%). Thus, P5 displayed the highest chemo suppressive activity, followed by P3 when compared to P4, indicating the importance of the 6”-OCH3 substitution on the quinolinyl ring for antiplasmodial activity. The activity of P5 at 100 mg kg-1 is close to that of 25 mg kg-1 chloroquine, therefore P5 is a potential antimalarial compound with a novel target. P3 and P5 are new compounds not reported in any chemical literature.

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