Design, Synthesis, Biological Evaluation, 2D-QSAR Modeling, and Molecular Docking Studies of Novel 1H-3-Indolyl Derivatives as Significant Antioxidants.
Int J Mol Sci
; 22(19)2021 Sep 27.
Article
em En
| MEDLINE
| ID: mdl-34638734
ABSTRACT
Novel candidates of 3-(4-(thiophen-2-yl)-pyridin/pyran/pyrimidin/pyrazol-2-yl)-1H-indole derivatives (2-12) were designed by pairing the pyridine/pyrane/pyrimidine/pyrazole heterocycles with indole and thiophene to investigate their potential activities as (2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) inhibitors. The purpose of these derivatives' modification is to create high-efficiency antioxidants, especially against ABTS, as a result of the efficiency of this set of key heterocycles in the inhibition of ROS. Herein, 2D QSAR modeling was performed to recommend the most promising members for further in vitro investigations. Furthermore, the pharmacological assay for antioxidant activity evaluation of the yielded indole-based heterocycles was tested against ABTS (2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid); by utilizing ascorbic acid as the standard. Candidate 10 showed higher antioxidant activity (IC50 = 28.23 µg/mL) than ascorbic acid itself which achieved (IC50 = 30.03 µg/mL). Moreover, molecular docking studies were performed for the newly designed and synthesized drug candidates to propose their mechanism of action as promising cytochrome c peroxidase inhibitors compared to ascorbic acid as a reference standard. Our findings could be promising in the medicinal chemistry scope for further optimization of the newly designed and synthesized compounds regarding the introduced structure-activity relationship study (SAR) in order to get a superior antioxidant lead compound in the near future.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Simulação de Acoplamento Molecular
/
Indóis
/
Antioxidantes
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Egito