| Literature DB >> 35690595 |
Rasoul Motahari1, Mohammad Amin Boshagh2, Setareh Moghimi3, Fariba Peytam3, Zaman Hasanvand1, Tayebeh Oghabi Bakhshaiesh2, Roham Foroumadi4, Hamidreza Bijanzadeh5, Loghman Firoozpour1, Ali Khalaj1, Rezvan Esmaeili6, Alireza Foroumadi7,8.
Abstract
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 μg/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.Entities:
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Year: 2022 PMID： 35690595 PMCID： PMC9188586 DOI： 10.1038/s41598-022-13515-4
Source DB: PubMed Journal: Sci Rep ISSN： 2045-2322 Impact factor: 4.996