Discovery of a Highly Potent and Novel Gambogic Acid Derivative as an Anticancer Drug Candidate.
Anticancer Agents Med Chem
; 21(9): 1110-1119, 2021.
Article
em En
| MEDLINE
| ID: mdl-32268871
ABSTRACT
BACKGROUND AND PURPOSE:
Gambogic Acid (GA), a promising anti-cancer agent isolated from the resin of Garcinia species in Southeast Asia, exhibits high potency in inhibiting a wide variety of cancer cells' growth. Moreover, the fact that it is amenable to chemical modification makes GA an attractive molecule for the development of anti-cancer agents.METHODS:
Gambogic acid-3-(4-pyrimidinyloxy) propyl ester (compound 4) was derived from the reaction between 4-hydroxypropoxy pyrimidine and GA. Its structure was elucidated by comprehensive analysis of ESIMS, HRESIMS, 1 D NMR data. Anti-tumor activities of compound 4 and GA in vitro against HepG-2, A549 and MCF-7 cells were investigated by MTT assay. FITC/PI dye was used to test apoptosis. The binding affinity difference of compound 4 and GA binding to IKKß was studied by using Discovery Studio 2016.RESULTS:
Compound 4 was successfully synthesized and showed strong inhibitory effects on HepG-2, A549 and MCF-7 cells lines with an IC50 value of 1.49±0.11, 1.37±0.06 and 0.64±0.16µM, respectively. Molecular docking study demonstrated that four more hydrogen bonds were established between IKKß and compound 4, compared with GA.CONCLUSION:
Our results suggested that compound 4 showed significant effects in inducing apoptosis. Further molecular docking study indicated that the introduction of pyrimidine could improve GA's binding affinity to IKKß. Compound 4 may serve as a potential lead compound for the development of new anti-cancer drugs.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Xantonas
/
Descoberta de Drogas
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article