Synthesis and Evaluation of N-(3-Trifluoroacetyl-indol-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 trifl...
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doaj-4b33b6e8d9cb4dd78634efd8406739ec2020-11-25T00:57:52ZengMDPI AGMolecules1420-30492017-07-01227109910.3390/molecules22071099molecules22071099Synthesis and Evaluation of N-(3-Trifluoroacetyl-indol-7-yl) Acetamides for Potential In Vitro Antiplasmodial PropertiesMalose J. Mphahlele0Mmakwena M. Mmonwa1Yee Siew Choong2Department of Chemistry, College of Science, Engineering and Technology, University of South Africa, Private Bag X06, Florida 1710, South AfricaDepartment of Chemistry, College of Science, Engineering and Technology, University of South Africa, Private Bag X06, Florida 1710, South AfricaInstitute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 11800 Minden, Penang, MalaysiaA 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.https://www.mdpi.com/1420-3049/22/7/1099N-(2,5-diaryl-1H-indol-7-yl)acetamidesN-(3-trifluoroacetylindol-7-yl)acetamidesantiplasmodial activitycytotoxicitymolecular docking |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Malose J. Mphahlele Mmakwena M. Mmonwa Yee Siew Choong |
spellingShingle |
Malose J. Mphahlele Mmakwena M. Mmonwa Yee Siew Choong Synthesis and Evaluation of N-(3-Trifluoroacetyl-indol-7-yl) Acetamides for Potential In Vitro Antiplasmodial Properties Molecules N-(2,5-diaryl-1H-indol-7-yl)acetamides N-(3-trifluoroacetylindol-7-yl)acetamides antiplasmodial activity cytotoxicity molecular docking |
author_facet |
Malose J. Mphahlele Mmakwena M. Mmonwa Yee Siew Choong |
author_sort |
Malose J. Mphahlele |
title |
Synthesis and Evaluation of N-(3-Trifluoroacetyl-indol-7-yl) Acetamides for Potential In Vitro Antiplasmodial Properties |
title_short |
Synthesis and Evaluation of N-(3-Trifluoroacetyl-indol-7-yl) Acetamides for Potential In Vitro Antiplasmodial Properties |
title_full |
Synthesis and Evaluation of N-(3-Trifluoroacetyl-indol-7-yl) Acetamides for Potential In Vitro Antiplasmodial Properties |
title_fullStr |
Synthesis and Evaluation of N-(3-Trifluoroacetyl-indol-7-yl) Acetamides for Potential In Vitro Antiplasmodial Properties |
title_full_unstemmed |
Synthesis and Evaluation of N-(3-Trifluoroacetyl-indol-7-yl) Acetamides for Potential In Vitro Antiplasmodial Properties |
title_sort |
synthesis and evaluation of n-(3-trifluoroacetyl-indol-7-yl) acetamides for potential in vitro antiplasmodial properties |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2017-07-01 |
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. |
topic |
N-(2,5-diaryl-1H-indol-7-yl)acetamides N-(3-trifluoroacetylindol-7-yl)acetamides antiplasmodial activity cytotoxicity molecular docking |
url |
https://www.mdpi.com/1420-3049/22/7/1099 |
work_keys_str_mv |
AT malosejmphahlele synthesisandevaluationofn3trifluoroacetylindol7ylacetamidesforpotentialinvitroantiplasmodialproperties AT mmakwenammmonwa synthesisandevaluationofn3trifluoroacetylindol7ylacetamidesforpotentialinvitroantiplasmodialproperties AT yeesiewchoong synthesisandevaluationofn3trifluoroacetylindol7ylacetamidesforpotentialinvitroantiplasmodialproperties |
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1725222490007928832 |