The impact of 9-azaglycophymine and phenylguanidine derivatives on the proliferation of various breast cancer cell lines in vitro and in vivo

被引：0

作者：

Morgan, Ibrahim ^{[1
]}

Rennert, Robert ^{[1
]}

Berger, Robert ^{[1
]}

Jelaca, Sanja ^{[2
]}

Maksimovic-Ivanic, Danijela ^{[2
]}

Dunderovic, Dusko ^{[3
]}

Mijatovic, Sanja ^{[2
]}

Kaluderovic, Goran N. ^{[1
,4
]}

Wessjohann, Ludger A. ^{[1
]}

机构：

[1] Leibniz Inst Plant Biochem, Dept Bioorgan Chem, Weinberg 3, D-06120 Halle, Saale, Germany

[2] Univ Belgrade, Inst Biol Res Sinisa Stankovic, Natl Inst Republ Serbia, Dept Immunol, Bulevar Despota Stefana 142, Belgrade 11108, Serbia

[3] Univ Belgrade, Inst Pathol, Fac Med, Dr Subotica 1, Belgrade 11000, Serbia

[4] Univ Appl Sci Merseburg, Dept Engn & Nat Sci, Eberhard Leibnitz Str 2, D-06217 Merseburg, Germany

来源：

SCIENTIFIC REPORTS | 2024年 / 14卷 / 01期

关键词：

Quinazoline; Quinazolinone; Anticancer; Apoptosis; Breast cancer; Structure-activity-relationship; NITROAROMATIC COMPOUNDS; TUMOR NECROSIS; LUNG-CANCER; INHIBITORS; DISCOVERY; THERAPY; DEATH;

D O I：

10.1038/s41598-024-71624-8

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Quinazolinones, particularly 9-azaglycophymines, and closely related derivatives and precursors were tested in vitro against various breast cancer cell lines representing the major types of breast tumors. Among the 49 compounds tested, azaglycophymine derivative 19 with an electron-withdrawing substituent demonstrated the most significant anti-proliferative effects, with IC50 values of around 4 mu M. Extensive cell-based investigations revealed that compound 19 induced caspase-dependent apoptosis in HCC1937 (human TNBC), BT-474 (human HER2+/HR+), and 4T1 (mouse TNBC) cells. In contrast, in MDA-MB-468 (human TNBC) and MCF-7 (human HR+) cells, the cell death was induced via a non-apoptotic pathway. The in vivo efficacy of compound 19 was validated using a syngeneic orthotopic 4T1 model in BALB/c mice, resulting in significant reduction of 4T1 breast tumor growth upon intraperitoneal (i.p.) application of doses of 5 or 20 mg/kg. These findings highlight the potential of compound 19 as a promising scaffold for the development of new therapeutic agents for various types of breast cancer and a first structure-activity insight.

引用

页数：13

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