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Synthesis, antimalarial activities of secondary amine-substituted eugenol compounds against plasmodium falciparum and in silico molecular docking analysis

Multi-resistance cases with antimalarial drugs had been developed in over the years. One of the ways of developing antimalarial drugs is to focus on searching for the potential antifolate inhibitors against Plasmodium sp. from synthetic or natural products. The aims of this research was to synthesis...

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Main Authors: Syahri, Jufrizal, Hilma, Rahmiwati, Nurlaili,, Sari, Meidita Kemala, Frimayanti, Neni, Amatul Hamizah Ali,, Jalifah Latip,
Format: Article
Language:English
Published: Penerbit Universiti Kebangsaan Malaysia 2023
Online Access:http://journalarticle.ukm.my/23358/1/SD%209.pdf
http://journalarticle.ukm.my/23358/
https://www.ukm.my/jsm/english_journals/vol52num12_2023/contentsVol52num12_2023.html
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spelling my-ukm.journal.233582024-04-17T07:18:11Z http://journalarticle.ukm.my/23358/ Synthesis, antimalarial activities of secondary amine-substituted eugenol compounds against plasmodium falciparum and in silico molecular docking analysis Syahri, Jufrizal Hilma, Rahmiwati Nurlaili, Sari, Meidita Kemala Frimayanti, Neni Amatul Hamizah Ali, Jalifah Latip, Multi-resistance cases with antimalarial drugs had been developed in over the years. One of the ways of developing antimalarial drugs is to focus on searching for the potential antifolate inhibitors against Plasmodium sp. from synthetic or natural products. The aims of this research was to synthesis secondary amine-substituted eugenol compounds through the Mannich reaction for antimalarial evaluation using Plasmodium falciparum 3D7. The compounds were also evaluated on Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) as a protein target and the compounds’ drug-likeness properties were determined. Five secondary amine-substituted eugenol compounds (1a-e) were synthesized via substitution of the secondary amine i.e., pyrrolidine, piperidine, methyl piperidine, and morpholine in the eugenol structures. The plasmodium lactate dehydrogenase assay (pLDH) showed that 1a and 1c had good antimalarial effects against P. falciparum 3D7 with the IC50s values of 0.89 µM and 0.62 µM, respectively. The molecular docking analysis showed that 1a and 1c had perfect interaction with PfDHFR-TS (PDB ID: 1J3I) with strong hydrogen bond interactions occurring with PfDHFR-TS protein. The eugenol derivatives 1a and 1c exerted CDOCKER binding energies of -6.1407 and -6.6536 kcal/mol, respectively. Based on this research, it was found that PfDHFR-TS is a plausible protein target for the synthesized secondary amine-substituted eugenol in P. falciparum infection. The substitution of a secondary amine group for eugenol significantly enhanced the antimalarial properties of the compounds. Thus, eugenol derivatives are potential compounds to be pursued to combat folate resistance in malarial infection. Penerbit Universiti Kebangsaan Malaysia 2023 Article PeerReviewed application/pdf en http://journalarticle.ukm.my/23358/1/SD%209.pdf Syahri, Jufrizal and Hilma, Rahmiwati and Nurlaili, and Sari, Meidita Kemala and Frimayanti, Neni and Amatul Hamizah Ali, and Jalifah Latip, (2023) Synthesis, antimalarial activities of secondary amine-substituted eugenol compounds against plasmodium falciparum and in silico molecular docking analysis. Sains Malaysiana, 52 (12). pp. 3463-3474. ISSN 0126-6039 https://www.ukm.my/jsm/english_journals/vol52num12_2023/contentsVol52num12_2023.html
institution Universiti Kebangsaan Malaysia
building Tun Sri Lanang Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Kebangsaan Malaysia
content_source UKM Journal Article Repository
url_provider http://journalarticle.ukm.my/
language English
description Multi-resistance cases with antimalarial drugs had been developed in over the years. One of the ways of developing antimalarial drugs is to focus on searching for the potential antifolate inhibitors against Plasmodium sp. from synthetic or natural products. The aims of this research was to synthesis secondary amine-substituted eugenol compounds through the Mannich reaction for antimalarial evaluation using Plasmodium falciparum 3D7. The compounds were also evaluated on Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) as a protein target and the compounds’ drug-likeness properties were determined. Five secondary amine-substituted eugenol compounds (1a-e) were synthesized via substitution of the secondary amine i.e., pyrrolidine, piperidine, methyl piperidine, and morpholine in the eugenol structures. The plasmodium lactate dehydrogenase assay (pLDH) showed that 1a and 1c had good antimalarial effects against P. falciparum 3D7 with the IC50s values of 0.89 µM and 0.62 µM, respectively. The molecular docking analysis showed that 1a and 1c had perfect interaction with PfDHFR-TS (PDB ID: 1J3I) with strong hydrogen bond interactions occurring with PfDHFR-TS protein. The eugenol derivatives 1a and 1c exerted CDOCKER binding energies of -6.1407 and -6.6536 kcal/mol, respectively. Based on this research, it was found that PfDHFR-TS is a plausible protein target for the synthesized secondary amine-substituted eugenol in P. falciparum infection. The substitution of a secondary amine group for eugenol significantly enhanced the antimalarial properties of the compounds. Thus, eugenol derivatives are potential compounds to be pursued to combat folate resistance in malarial infection.
format Article
author Syahri, Jufrizal
Hilma, Rahmiwati
Nurlaili,
Sari, Meidita Kemala
Frimayanti, Neni
Amatul Hamizah Ali,
Jalifah Latip,
spellingShingle Syahri, Jufrizal
Hilma, Rahmiwati
Nurlaili,
Sari, Meidita Kemala
Frimayanti, Neni
Amatul Hamizah Ali,
Jalifah Latip,
Synthesis, antimalarial activities of secondary amine-substituted eugenol compounds against plasmodium falciparum and in silico molecular docking analysis
author_facet Syahri, Jufrizal
Hilma, Rahmiwati
Nurlaili,
Sari, Meidita Kemala
Frimayanti, Neni
Amatul Hamizah Ali,
Jalifah Latip,
author_sort Syahri, Jufrizal
title Synthesis, antimalarial activities of secondary amine-substituted eugenol compounds against plasmodium falciparum and in silico molecular docking analysis
title_short Synthesis, antimalarial activities of secondary amine-substituted eugenol compounds against plasmodium falciparum and in silico molecular docking analysis
title_full Synthesis, antimalarial activities of secondary amine-substituted eugenol compounds against plasmodium falciparum and in silico molecular docking analysis
title_fullStr Synthesis, antimalarial activities of secondary amine-substituted eugenol compounds against plasmodium falciparum and in silico molecular docking analysis
title_full_unstemmed Synthesis, antimalarial activities of secondary amine-substituted eugenol compounds against plasmodium falciparum and in silico molecular docking analysis
title_sort synthesis, antimalarial activities of secondary amine-substituted eugenol compounds against plasmodium falciparum and in silico molecular docking analysis
publisher Penerbit Universiti Kebangsaan Malaysia
publishDate 2023
url http://journalarticle.ukm.my/23358/1/SD%209.pdf
http://journalarticle.ukm.my/23358/
https://www.ukm.my/jsm/english_journals/vol52num12_2023/contentsVol52num12_2023.html
_version_ 1797908406198075392
score 13.211869

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