Design, Synthesis, and Biological Evaluation of Artemisinin-Piperazine-Phosphoramide Mustard Hybrids as Potential Anticancer Agents.
ChemMedChem
; 17(17): e202200239, 2022 09 05.
Article
em En
| MEDLINE
| ID: mdl-35771689
ABSTRACT
A series of novel artemisinin-piperazine-phosphoramide mustard (PPM) hybrids were designed and synthesized by incorporating phosphoramide mustard (PM) into dihydroartemisinin (DHA) via an efficient, catalyst-free two-step sequential substitution. Artemisinin-PPM hybrids showed better cytotoxic potency against HepG2 cells than both the parent DHA and the reference, vincristine (VCR). Structure-activity relationship (SAR) studies showed that the cytotoxicity was significantly enhanced by the introduction of a thiazole moiety. Hybrid 7 h, the most potent compound with the highest selectivity index IC50 (HEK-293T)/IC50 (HepG2)=16, displayed 7.4-fold stronger potency than VCR against HepG2 cells. In addition, hybrid 7 h was substantially more cytotoxic on all human cancer cells tested than on the corresponding non-cancerous cells. Flow cytometric analysis showed that 7 h significantly blocked the cell cycle in the G0/G1 phase and induced apoptosis in a concentration-dependent manner.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artemisininas
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
ChemMedChem
Ano de publicação:
2022
Tipo de documento:
Article