Green Synthesis of a Novel Phytoalexin Derivative: In Silico Profiling, Apoptotic Induction, and Antiproliferative Activity against MCF-7 cells - From Vineyards to Potent Anticancer Drug Molecule.
Anticancer Agents Med Chem
; 24(1): 66-76, 2024.
Article
em En
| MEDLINE
| ID: mdl-37936468
ABSTRACT
BACKGROUND:
Resveratrol's structural similarity to commercialized anti-breast cancer medications such as Tamoxifen underlines its potential as a promising option for developing successful anti-breast cancer drugs. However, the pharmacokinetic issues associated with resveratrol, such as its low bioavailability, have piqued the attention of researchers in developing novel derivatives.METHODS:
A novel phytoalexin derivative, RsvD1, was successfully synthesized using resveratrol extracted from green grape peels as a precursor to investigate its anti-breast cancer efficacy on Estrogen receptor (ER) positive and negative breast cancer cells.RESULTS:
The comparative analysis revealed that RsvD1 exhibited remarkable radical scavenging ability (IC50 = 2.21 µg/mL), surpassing the control, Trolox (IC50 = 6.3 µg/mL). Furthermore, RsvD1 demonstrated enhanced and selective antiproliferative activity against ER-positive MCF-7 cells (IC50 = 20.09 µg/mL) compared to resveratrol, the parent molecule (IC50 = 30.90 µg/mL). Further investigations unveiled that RsvD1 induced apoptosis and DNA damage in MCF-7 cells, leading to cell cycle arrest at the G0/G1 phase after 24 hours of incubation. RTqPCR gene expression analysis indicated that RsvD1 down-regulated the CAXII (ER-dependent) genes. In silico predictions demonstrated that RsvD1 possesses promising potential as a drug candidate due to its drug-like characteristics and favourable ADMET profile. Moreover, molecular docking studies provided insights into the theoretical binding mode between RsvD1 and ERα protein.CONCLUSION:
The study highlights the therapeutic potential of the synthesized resveratrol derivative, RsvD1, positioning it as a promising scaffold for developing novel analogues with improved therapeutic properties and selectivity, specifically targeting ER+ breast cancer cells. Moreover, the compound's non-cytotoxic yet antiproliferative properties, coupled with its capability to induce programmed cell death and cell cycle arrest, enhance its potential as a highly effective drug candidate. As a result, this paves a promising path for the development of innovative and selective inhibitors targeting ER+ breast cancer with enhanced efficacy.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Antineoplásicos
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article