Thienopyrimidine‐based agents bearing diphenylurea: Design, synthesis, and evaluation of antiproliferative and antiangiogenic activity. Issue 3 (21st November 2022)

• Record Type: Journal Article
• Authors: Mohammadian, Esmaeil; Oghabi Bakhshaiesh, Tayebeh; Jouyban, Abolghasem; Nazeri, Elahe; Hasanvand, Zaman; Moghimi, Setareh; Motahari, Rasoul; Firoozpour, Loghman; Bijanzadeh, Hamidreza; Alizadeh Sani, Mahmood; Hosseinzadeh, Elaheh; Esmaeili, Rezvan; Foroumadi, Alireza
• Is Part Of: Archiv der Pharmazie. Volume 356:Issue 3(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-11-21
• Subjects: angiogenesis -- apoptotic effects -- CAM assay -- diaryl urea -- VEGFR‐2; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.202200349
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract: An important role has been considered for the vascular endothelial growth factor receptor 2 (VEGFR‐2) in the angiogenesis process, so that its inhibition is an important scientific way for cancer treatment. In this work, new thienopyrimidine derivatives were synthesized and evaluated. Compared with sorafenib, the majority of the target compounds had antiproliferative activity against the PC3, HepG2, MCF7, SW480, and HUVEC cell lines, especially 9h with IC50 values of 4.5–15.1 μM, confirming the noticeable cytotoxic effects on the listed cell lines (PC3, HepG2, SW480, and HUVEC). Analyses by flow cytometry on SW480 and HUVEC cells revealed that 9n, 9k, 9h, and 9q led to apoptotic cell death. The result of the chick chorioallantoic membrane assay showed that 9h effectively reduced the number of corresponding blood vessels. Finally, the inhibitory effect on VEGFR‐2 phosphorylation was considered as the outcome of Western blot analysis of compound 9h . Abstract : New thienopyrimidine derivatives were synthesized and evaluated as inhibitors of vascular endothelial growth factor receptor 2 (VEGFR‐2). Most of the target compounds had antiproliferative activity against PC3, HepG2, MCF7, SW480, and HUVEC cells (9h : IC50 = 4.5–15.1 μM). In the chick chorioallantoic membrane assay, 9h effectively reduced the number of corresponding blood vessels.