Malose J., Mphahlele and Mmakwena M., Mmonwa and Yee, Siew Choong
(2017)
Synthesis and Evaluation of N-(3-Trifluoroacetylindol-
7-yl) Acetamides for Potential In Vitro Antiplasmodial Properties.
Molecules, 22 (7).
pp. 1-18.
ISSN 1420-3049
Abstract
A series of novel N-((2,5-diaryl-3-trifluoroacetyl)-1H-indol-7-yl)acetamides has been prepared
via a successive and one-pot reaction sequence involving initial trifluoroacetic acid-mediated Beckmann
rearrangement of the oximes derived from the 1-(2,5-diaryl-1H-indol-7-yl)ethanones, followed
by trifluoroacetylation of the incipient N-(2,5-diaryl-1H-indol-7-yl)-acetamides with trifluoroacetic
anhydride. The prepared compounds were evaluated for potential in vitro antiplasmodial properties.
Preliminary results from antiplasmodial activity against the chloroquine-sensitive 3D7 strain of
Plasmodium falciparum revealed that a combination of 2-(4-flurophenyl)- and 5-(4-fluorophenyl) or
2-(4-flurophenyl)- and 4-fluorostyryl groups in compounds 3(a,f) and 4(a,g), for example, is required for
biological activity for both series of compounds. Their possible mode of action against the plasmodial
parasite is explained theoretically through molecular docking of the most active compounds against
the parasite lactate dehydrogenase (pLDH). These compounds were docked at the entrance of NAD+
in pLDH presumably hindering entry of lactate to cause the observed inhibition effect of pLDH.
The four compounds were found to exhibit low toxicity against monkey kidney Vero cells at the highest
concentrations tested.
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