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Chalcone Mannich base derivatives: synthesis, antimalarial activities against , and molecular docking analysis
Development and discovery of new antimalarial drugs are needed to overcome the multi-resistance of Plasmodium parasites to commercially available drugs. Modifying the substitutions on the amine groups has been shown to increase antimalarial activities and decrease cross-resistance with chloroquine....
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Published in: | RSC advances 2023-12, Vol.13 (51), p.3635-3647 |
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Main Authors: | , , , , , , , , , |
Format: | Article |
Language: | |
Online Access: | Get full text |
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Summary: | Development and discovery of new antimalarial drugs are needed to overcome the multi-resistance of
Plasmodium
parasites to commercially available drugs. Modifying the substitutions on the amine groups has been shown to increase antimalarial activities and decrease cross-resistance with chloroquine. In this study, we have synthesized several chalcone derivatives
via
the substitution of aminoalkyl groups into the aromatic chalcone ring using the Mannich-type reaction. The chalcone derivatives were evaluated for their antimalarial properties against
Plasmodium knowlesi
A1H1 and
P. falciparum
3D7, as well as their molecular docking on
Plasmodium falciparum
dihydrofolate reductases-thymidylate synthase (PfDHFR-TS). Data from
in vitro
evaluation showed that chalcone Mannich-type base derivatives
2a
,
2e
, and
2h
displayed potential antimalarial activities against
P. knowlesi
with EC
50
of 2.64, 2.98, and 0.10 μM, respectively, and
P. falciparum
3D7 with EC
50
of 0.08, 2.69, and 0.15 μM, respectively. The synthesized compounds
2a
,
2e
, and
2h
exerted high selectivity index (SI > 10) values on the A1H1 and 3D7 strains. The molecular docking analysis on PfDHFR-TS supported the
in vitro
assay of
2a
,
2e
, and
2h
by displaying CDOCKER energy of −48.224, −43.292, and −45.851 kcal mol
−1
. Therefore, the evidence obtained here supports that PfDHFR-TS is a putative molecular target for the synthesized compound.
Research on the antimalarial effect of aminoalkyl chalcone derivatives against
Plasmodium falciparum
and
Plasmodium knowlesi
has bolstered efforts in drug discovery to combat cases of drug resistance. |
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ISSN: | 2046-2069 |
DOI: | 10.1039/d3ra05361j |