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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. [ABSTRACT FROM AUTHOR]

A series of new coumarin-containing compounds 3a-l and 4a-c was designed and synthesized based on the chalcone-type 4-amino-5-cinnamoylthiazole scaffold 2 , and screened for their in vitro anticancer and antioxidant activities. Representatively, the 2-thiomorpholinothiazole derivative 3k with IC 50 values of 7.5–16.9 μg/ml demonstrated good cytotoxic effects against tested cell lines MCF-7, HepG2 and SW480. Further investigation by flow cytometric analysis confirmed that this compound induces apoptotic cell death in MCF-7 cells and cause G1-phase arrest in the cell cycle. Moreover, most of compounds had intrinsic potential for radical scavenging activity and ferric-reducing power as investigated by DPPH and FRAP assays. [ABSTRACT FROM AUTHOR]

In this paper, we described the synthesis and cytotoxic activities of two new series of thieno[2,3- d ]pyrimidine and thieno[3,2- d ] pyrimidine derivatives. Most of the synthesized compounds had significant antiproliferative activities against PC3, MDA-MB-231, A549, and HeLa cell lines in comparison to the reference drug, erlotinib. Compounds N -(4-((3,5-dichlorophenyl)amino)thieno[2,3- d ]pyrimidin-6-yl)cinnamamide 8e and (E)- N -(4-((3,4-dichlorophenyl)amino)thieno[2,3- d ]pyrimidin-6-yl)-3-(4-methoxyphenyl)acrylamide 8g with IC 50 values of 4 nM and 33 nM, respectively, against HeLa cell line were chosen for further studies. The apoptosis induced activity and cell cycle arrest were determined and the results provided evidence that these compounds induced cell death via apoptosis and arrested cell growth in sub-G1 phase. In addition, western blot analysis manifested the promising result of suppressing the EGFR signaling pathway (p-EGFR/p-ERK1/2). The docking studies appreciated the considerable potency of compound 8e based on hydrogen and covalent binding interactions. Eventually, in silico pharmacokinetic prediction indicated the acceptable bioavailability of all final compounds. Image 1 • Two series of thienopyrimidine-based compounds were designed and synthesized. • 8e was the most potent compound with nanomolar IC 50 value on HeLa cell line. • 8e was 720 times more selective on lung cancer cell than normal lung cell. • Western blot analysis of 8e revealed EGFR and ERK1/2 phosphorylation inhibition. [ABSTRACT FROM AUTHOR]