Design, synthesis and evaluation of novel tetrahydropyridothienopyrimidin-ureas as cytotoxic and anti-angiogenic agents

被引：8

作者：

Motahari, Rasoul ^{[1
]}

Boshagh, Mohammad Amin ^{[2
]}

Moghimi, Setareh ^{[3
]}

Peytam, Fariba ^{[3
]}

Hasanvand, Zaman ^{[1
]}

Bakhshaiesh, Tayebeh Oghabi ^{[2
]}

Foroumadi, Roham ^{[4
]}

Bijanzadeh, Hamidreza ^{[5
]}

Firoozpour, Loghman ^{[1
]}

Khalaj, Ali ^{[1
]}

Esmaeili, Rezvan ^{[2
]}

Foroumadi, Alireza ^{[1
,3
]}

机构：

[1] Univ Tehran Med Sci, Fac Pharm, Dept Med Chem, Tehran, Iran

[2] ACECR, Motamed Canc Inst, Genet Dept, Breast Canc Res Ctr, Tehran, Iran

[3] Univ Tehran Med Sci, Drug Design & Dev Res Ctr, Inst Pharmaceut Sci TIPS, Tehran, Iran

[4] Univ Tehran Med Sci, Sch Med, Dept Pharmacol, Tehran, Iran

[5] Tarbiat Modares Univ, Fac Nat Resources & Marine Sci, Dept Environm Sci, Tehran, Iran

来源：

SCIENTIFIC REPORTS | 2022年 / 12卷 / 01期

关键词：

VEGFR-2; INHIBITORS; DERIVATIVES; DISCOVERY; SCAFFOLD; CANCER;

D O I：

10.1038/s41598-022-13515-4

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：

The novel derivatives of tetrahydropyridothienopyrimidine-based compounds have been designed and efficiently synthesized with good yields through seven steps reaction. The anticancer activity of compounds 11a-y has been evaluated against MCF-7, PC-3, HEPG-2, SW-480, and HUVEC cell lines by MTT assay. The target compounds showed IC50 values between 2.81-29.6 mu g/mL and were compared with sorafenib as a reference drug. Among them, compound 11n showed high cytotoxic activity against four out of five examined cell lines and was 14 times more selective against MRC5. The flow cytometric analysis confirmed the induction of apoptotic cell death by this compound against HUVEC and MCF-7 cells. In addition, 11n caused sub-G1 phase arrest in the cell cycle arrest. Besides, this compound induced anti-angiogenesis in CAM assay and increased the level of caspase-3 by 5.2 fold. The western-blot analysis of the most active compound, 11n, revealed the inhibition of VEGFR-2 phosphorylation. Molecular docking study also showed the important interactions for compound 11n.

引用

页数：17

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