Design, Synthesis and Antimalarial Evaluation of New Trimethoxy Benzaldehyde Chalcones
doi.org/10.26538/tjnpr/v3i7.2
Keywords:
Malaria,, Protease,, Chalcones, Synthesis,, Schmidt-Claisen condensationAbstract
Proteases are validated drug target for inhibition of Plasmodium falciparum, the most virulent malaria parasite. This study guided by previous reports, designed trimethoxy benzaldehyde chalcone derivatives as potential protease inhibitors and antimalarial agents. They were synthesized by Schmidt-Claisen condensation reaction. The structures of these compounds were established using Fourier transform infrared (FT-IR), Proton, Carbon-13, as well as two- dimensional nuclear magnetic resonance (NMR) spectroscopy, and Mass Spectrometry (MS). The synthesized compounds were screened for in-vivo antimalarial activity in mice infected with Plasmodium berghei parasite, using curative model. (E)-1-(2,4-dimethoxyphenyl)-3-(2,3,4- trimethoxy-phenyl) prop-2-en-1-one (P2) displayed a significant activity, with activity comparable to that of quinine (10 mgkg-1) and chloroquine (25 mg kg-1) at a dose of 100 mgkg-1 in the curative test. However, (E)-1,3-bis(2,3,4-trimethoxyphenyl) prop-2-en-1-one (P1) and (E)-1-(2,4-dichlorophenyl)-3-(2,3,4-trimethoxyphenyl) prop-2-en-1-one (P13) did not show any significant activity (p < 0.05). Compound P2 was found to be devoid of electron deficient ring A (benzaldehyde ring). This suggests that, electron density on the rings are not determinants for antimalarial activity of the chalcone as proposed earlier and, present compound P2 as a candidate for further optimization and evaluation for prophylactic and suppressive activities.
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