Novel C3-Methylene-Bridged Indole Derivatives with and without Substituents at N1: The Influence of Substituents on Their Hemolytic, Cytoprotective, and Antimicrobial Activity
Type
Journal article
Language
English
Date issued
2024
Author
Babijczuk, Karolina
Berdzik, Natalia
Nowak, Damian
Warżajtis, Beata
Rychlewska, Urszula
Mrówczyńska, Lucyna
Jasiewicz, Beata
Faculty
Wydział Rolnictwa, Ogrodnictwa i Biotechnologii
PBN discipline
agriculture and horticulture
Journal
International Journal of Molecular Sciences
ISSN
1422-0067
Web address
Volume
25
Number
10
Pages from-to
art. 5364
Abstract (EN)
Alkaloids are natural compounds useful as scaffolds for discovering new bioactive molecules. This study utilized alkaloid gramine to synthesize two groups of C3-substituted indole derivatives, which were either functionalized at N1 or not. The compounds were characterized by spectroscopic methods. The protective effects of the new compounds against in vitro oxidative hemolysis induced by standard oxidant 2,2′-azobis(2-amidinopropane dihydro chloride (AAPH) on human erythrocytes as a cell model were investigated. Additionally, the compounds were screened for antimicrobial activity. The results indicated that most of the indole derivatives devoid of the N1 substitution exhibited strong cytoprotective properties. The docking studies supported the affinities of selected indole-based ligands as potential antioxidants. Furthermore, the derivatives obtained exhibited potent fungicidal properties. The structures of the eight derivatives possessing indole moiety bridged to the imidazole-, benzimidazole-, thiazole-, benzothiazole-, and 5-methylbenzothiazoline-2-thiones were determined by X-ray diffraction. The C=S bond lengths in the thioamide fragment pointed to the involvement of zwitterionic structures of varying contribution. The predominance of zwitterionic mesomers may explain the lack of cytoprotective properties, while steric effects, which limit multiple the hydrogen-bond acceptor properties of a thione sulfur, seem to be responsible for the high hemolytic activity.
License
CC-BY - Attribution
Open access date
May 14, 2024