Isatin-indoloquinoxaline click adducts with a potential to overcome platinum-based drug-resistance in ovarian cancer.
Bioorg Chem
; 142: 106953, 2024 01.
Article
em En
| MEDLINE
| ID: mdl-37925887
ABSTRACT
Herein, a series of isatin tethered indolo[2,3-b]quinoxaline hybrids was synthesized by considering the pharmacophoric features of known DNA intercalators and topoisomerase II inhibitors. The anti-proliferative properties of the synthesized compounds were evaluated against ovarian cancer cell lines (SKOV-3 and Hey A8). Four of the compounds exhibited promising anti-proliferative activities, with one of them being 10-fold more potent than cisplatin against drug-resistant Hey A8 cells. Further investigations were carried out to determine the DNA intercalating affinities of the most active compounds as potential mechanisms for their anti-proliferative activities. ADMET in silico studies were performed to assess the physicochemical, pharmacokinetics, and toxicity parameters of active compounds. This study, to the best of our knowledge, is the first report on the potential of isatin-indoloquinoxaline hybrids as structural blueprints for the development of new DNA intercalators. Additionally, it explores their potential to circumvent platinum-based resistance in ovarian cancer.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
/
Isatina
/
Antineoplásicos
Limite:
Female
/
Humans
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Índia