Substituted 3-styryl-2-pyrazoline derivatives as an antimalaria : synthesis, in vitro assay, molecular docking, druglikeness analysis, and ADMET prediction
The synthesis, in vitro antimalarial assay, molecular docking, drug-likeness analysis, and ADMET prediction of substituted 3-styryl-2-pyrazoline derivatives as antimalaria have been conducted. The synthesis of N-phenyl (1a‒3a) and N-acetyl-substituted (1b‒3b) 3-styryl-2-pyrazolines was carried o...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Penerbit Universiti Kebangsaan Malaysia
2022
|
| Online Access: | http://journalarticle.ukm.my/20867/1/9.pdf http://journalarticle.ukm.my/20867/ https://www.ukm.my/jsm/malay_journals/jilid51bil10_2022/KandunganJilid51Bil10_2022.html |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Institution: | Universiti Kebangsaan Malaysia |
| Language: | English |
| Summary: | The synthesis, in vitro antimalarial assay, molecular docking, drug-likeness analysis, and ADMET prediction of
substituted 3-styryl-2-pyrazoline derivatives as antimalaria have been conducted. The synthesis of N-phenyl (1a‒3a)
and N-acetyl-substituted (1b‒3b) 3-styryl-2-pyrazolines was carried out using dibenzalacetone derivatives and
hydrazine hydrate or phenylhydrazine. An in vitro antimalarial assay was conducted against the chloroquine-sensitive
Plasmodium falciparum 3D7 strain, while molecular docking was performed toward the crystal protein of Plasmodium
falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) (PDB ID: 1J3I). Furthermore, the prediction
of drug-like properties was determined by assessing Lipinski’s rules, and the pharmacokinetic parameters were also
studied in-silico, including absorption, distribution, metabolism, excretion, and toxicity (ADMET). The in vitro assay
showed that 3a (IC50 0.101 µM) has excellent antimalarial activity, followed by 2a (0.177 µM), and 1b (0.258 µM).
Molecular docking has supported the in vitro assay by showing the lowest CDOCKER energy for 3a (‒56.316 kcal/
mol), then 2a (‒51.2603 kcal/mol), and 1b (‒48.8774 kcal/mol). The drug-like properties showed that all of the
prepared compounds were acceptable based on Lipinski’s rules and predicted to be potentially orally bioavailable.
The ADMET analysis provided information that 3a and 2a could be proposed as the best lead antimalarial drugs with
further modification to reduce the lipophilicity and toxicity properties. |
|---|