Novel Tetrahydro-[1,2,4]triazolo[3,4-a]isoquinoline Chalcones Suppress Breast Carcinoma through Cell Cycle Arrests and Apoptosis

被引：7

作者：

Darwish, Mahmoud I. M. ^{[1
,2
]}

Moustafa, Ahmed M. ^{[2
,3
]}

Youssef, Asmaa M. ^{[2
,4
]}

Mansour, Mohamed ^{[5
]}

Yousef, Ahmed I. ^{[6
]}

El Omri, Abdelfatteh ^{[7
]}

Shawki, Hossam H. ^{[2
,5
]}

Mohamed, Magda F. ^{[8
]}

Hassaneen, Hamdi M. ^{[8
]}

Abdelhamid, Ismail A. ^{[8
]}

Oishi, Hisashi ^{[2
]}

机构：

[1] Zagazig Univ, Fac Vet Med, Dept Biochem, Zagazig 44511, Egypt

[2] Nagoya City Univ, Dept Comparat & Expt Med, Grad Sch Med Sci, Nagoya 4678601, Japan

[3] Al Azhar Univ, Fac Sci, Zool Dept, Cairo 11884, Egypt

[4] Anim Hlth Res Inst, Agr Res Ctr, Giza 12619, Egypt

[5] Natl Gene Bank Egypt, Giza 12916, Egypt

[6] Beni Suef Univ, Fac Sci, Mol Physiol Div, Bani Suwayf 62511, Egypt

[7] Hamad Med Corp, Dept Surg, Surg Res Sect, Doha, Qatar

[8] Cairo Univ, Fac Sci, Dept Chem, Giza 12613, Egypt

来源：

MOLECULES | 2023年 / 28卷 / 08期

关键词：

breast cancer; chalcones; methoxy group effect; MDA; cell cycle; cytotoxicity; docking; cIAP1; BIOLOGICAL EVALUATION; IN-VITRO; ANTICANCER; DERIVATIVES; SERIES;

D O I：

10.3390/molecules28083338

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Chalcones are interesting anticancer drug candidates which have attracted much interest due to their unique structure and their extensive biological activity. Various functional modifications in chalcones have been reported, along with their pharmacological properties. In the current study, novel chalcone derivatives with the chemical base of tetrahydro-[1,2,4]triazolo[3,4-a]isoquinolin-3-yl)-3-arylprop-2-en-1-one were synthesized, and the structure of their molecules was confirmed through NMR spectroscopy. The antitumor activity of these newly synthesized chalcone derivatives was tested on mouse (Luc-4T1) and human (MDA-MB-231) breast cancer cell lines. The antiproliferative effect was evaluated through SRB screening and the MTT assay after 48 h of treatment at different concentrations. Interestingly, among the tested chalcone derivatives, chalcone analogues with a methoxy group were found to have significant anticancer activity and displayed gradient-dependent inhibition against breast cancer cell proliferation. The anticancer properties of these unique analogues were examined further by cytometric analysis of the cell cycle, quantitative PCR, and the caspases-Glo 3/7 assay. Chalcone methoxy derivatives showed the capability of cell cycle arrest and increased Bax/Bcl2 mRNA ratios as well as caspases 3/7 activity. The molecular docking analysis suggests that these chalcone methoxy derivatives may inhibit anti-apoptotic proteins, particularly cIAP1, BCL2, and EGFRK proteins. In conclusion, our findings confirm that chalcone methoxy derivatives could be considered to be potent drug candidates against breast cancer.

引用

页数：19