Synthesis and Evaluation of N-(3-Trifluoroacetylindol- 7-yl) Acetamides for Potential In Vitro Antiplasmodial Properties

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 tr...

Full description

Bibliographic Details
Main Authors: Malose J., Mphahlele, Mmakwena M., Mmonwa, Yee, Siew Choong
Format: Article
Language:English
Published: MDPI 2017
Subjects:
Online Access:http://eprints.usm.my/37238/1/%28Synthesis_and_Evaluation%29_molecules-22-01099.pdf
_version_ 1825833621303328768
author Malose J., Mphahlele
Mmakwena M., Mmonwa
Yee, Siew Choong
author_facet Malose J., Mphahlele
Mmakwena M., Mmonwa
Yee, Siew Choong
author_sort Malose J., Mphahlele
collection USM
description 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.
first_indexed 2024-03-06T15:10:34Z
format Article
id usm.eprints-37238
institution Universiti Sains Malaysia
language English
last_indexed 2024-03-06T15:10:34Z
publishDate 2017
publisher MDPI
record_format dspace
spelling usm.eprints-372382017-10-26T02:39:58Z http://eprints.usm.my/37238/ Synthesis and Evaluation of N-(3-Trifluoroacetylindol- 7-yl) Acetamides for Potential In Vitro Antiplasmodial Properties Malose J., Mphahlele Mmakwena M., Mmonwa Yee, Siew Choong R735-854 Medical education. Medical schools. Research 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. MDPI 2017 Article PeerReviewed application/pdf en http://eprints.usm.my/37238/1/%28Synthesis_and_Evaluation%29_molecules-22-01099.pdf 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 http://www.mdpi.com/1420-3049/22/7/1099
spellingShingle R735-854 Medical education. Medical schools. Research
Malose J., Mphahlele
Mmakwena M., Mmonwa
Yee, Siew Choong
Synthesis and Evaluation of N-(3-Trifluoroacetylindol- 7-yl) Acetamides for Potential In Vitro Antiplasmodial Properties
title Synthesis and Evaluation of N-(3-Trifluoroacetylindol- 7-yl) Acetamides for Potential In Vitro Antiplasmodial Properties
title_full Synthesis and Evaluation of N-(3-Trifluoroacetylindol- 7-yl) Acetamides for Potential In Vitro Antiplasmodial Properties
title_fullStr Synthesis and Evaluation of N-(3-Trifluoroacetylindol- 7-yl) Acetamides for Potential In Vitro Antiplasmodial Properties
title_full_unstemmed Synthesis and Evaluation of N-(3-Trifluoroacetylindol- 7-yl) Acetamides for Potential In Vitro Antiplasmodial Properties
title_short Synthesis and Evaluation of N-(3-Trifluoroacetylindol- 7-yl) Acetamides for Potential In Vitro Antiplasmodial Properties
title_sort synthesis and evaluation of n 3 trifluoroacetylindol 7 yl acetamides for potential in vitro antiplasmodial properties
topic R735-854 Medical education. Medical schools. Research
url http://eprints.usm.my/37238/1/%28Synthesis_and_Evaluation%29_molecules-22-01099.pdf
work_keys_str_mv AT malosejmphahlele synthesisandevaluationofn3trifluoroacetylindol7ylacetamidesforpotentialinvitroantiplasmodialproperties
AT mmakwenammmonwa synthesisandevaluationofn3trifluoroacetylindol7ylacetamidesforpotentialinvitroantiplasmodialproperties
AT yeesiewchoong synthesisandevaluationofn3trifluoroacetylindol7ylacetamidesforpotentialinvitroantiplasmodialproperties