Electro-organic synthesis of C-5 sulfenylated amino uracils: Optimization and exploring topoisomerase-I based anti-cancer profile.
Bioorg Chem
; 138: 106660, 2023 09.
Article
em En
| MEDLINE
| ID: mdl-37320914
ABSTRACT
Cancer is spreading worldwide and is one of the leading causes of death. The use of existing chemotherapeutic agents is frequently limited due to side effects. As a result, it is critical to investigate new agents for cancer treatment. In this context, we developed an electrochemical method for the synthesis of a series of thiol-linked pyrimidine derivatives (3a-3p) and explored their anti-cancer potential. The biological profile of the synthesized compounds was evaluated against breast (MDAMB-231 and MCF-7) and colorectal (HCT-116) cancer cell lines. 3b and 3d emerged to be the most potent agents, with IC50 values ranging between 0.98 to 2.45 µM. Target delineation studies followed by secondary anticancer parameters were evaluated for most potent compounds, 3b and 3d. The analysis revealed compounds possess DNA intercalation potential and selective inhibition towards human topoisomerase (hTopo1). The analysis was further corroborated by DNA binding studies and in silico-based molecular modeling studies that validated the intercalating binding mode between the compounds and the DNA.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Uracila
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Índia