Design, Synthesis, Cytotoxic Evaluation, and Molecular Docking of New Alkyl Triphenylphosphonium Curcumin Derivatives

被引:2
|
作者
Dang, Phu Hoang [1 ,3 ,4 ]
Tran, Tu Hoai [1 ,3 ,4 ]
Le, Tho Huu [1 ,3 ,4 ]
Nguyen, Thu-Ha Thi [2 ,3 ]
Vong, Long Binh [2 ,3 ]
Nguyen, Mai Thanh Thi [1 ,3 ,4 ]
Nguyen, Nhan Trung [1 ,3 ,4 ]
机构
[1] Univ Sci, Fac Chem, 227 Nguyen Van Cu St,Ward 4,Dist 5, Ho Chi Minh City, Vietnam
[2] Int Univ, Sch Biomed Engn, Sch Biomed Engn, Quarter 6, Ho Chi Minh City, Vietnam
[3] Vietnam Natl Univ Ho Chi Minh City, Ho Chi Minh City, Vietnam
[4] Univ Sci, Res Lab Drug Discovery & Dev, 227 Nguyen Van Cu St,Ward 4,Dist 5, Ho Chi Minh City, Vietnam
来源
CHEMISTRYSELECT | 2024年 / 9卷 / 10期
关键词
alkyl triphenylphosphonium; curcumin; estrogen receptor alpha; mitochondria-targeted; molecular docking; ESTROGEN-RECEPTOR; ER-ALPHA; MITOCHONDRIA; BIOAVAILABILITY; RECOGNITION; DELIVERY; AGONIST;
D O I
10.1002/slct.202400176
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Despite the previous anticancer effects of curcumin against various cancer cell lines, in vitro, pre-clinical, and clinical studies have faced constraints, particularly at high doses. Therefore, the mitochondria-targeted approach represents a promising trend in cancer drug development. This study successfully synthesized three new alkyl triphenylphosphonium ester curcumin derivatives (1-3) with good yield. They demonstrated cytotoxicity against MCF-7 cells with IC50 values of 49.72, 62.57, and 91.73 mu M, respectively. These values indicated higher potency than free curcumin (IC50>100 mu M). Molecular docking studies of curcumin and three derivatives 1-3 with two estrogen receptor alpha (ER alpha) ligand binding domains, 3ERT (antagonist recognition and antiproliferative function), and 1GWR (agonist recognition and pro-proliferative function), were carried out. These domains are important targets in hormone-dependent anticancer strategies. The favourable docking scores and key residue interactions suggested that these derivatives could be the potential antagonists. Three synthesized alkyl-TPP+ curcumin ester derivatives (1-3) demonstrated more potent cytotoxic efficacy than curcumin, particularly against the human MCF-7 breast cancer cell line. In addition, molecular docking studies suggested their potential as antagonists of ER alpha. The in silico ADMET data of three derivatives (1-3) showed compliance with the Lipinski rule and demonstrated their absorption, distribution, metabolism, and excretion properties.
引用
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页数:6
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