New functionalized 6‐thienylpyrimidine‐5‐carbonitriles as antiproliferative agents against human breast cancer cells

Abstract

6-Thienylpyrimidine-5-carbonitrile derivatives were synthesized and screened for their in vitro antiproliferative activities against two human breast cancer cell lines in comparison to 5-fluorouracil as a reference. Compounds 2, 3a-c, and 6b evolved as the most active congeners against both cell lines, while others showed selectivity for only one cell line. Compound 2 exerted its effect through inhibition of the epidermal growth factor receptor (EGFR), while 6b showed less aromatase inhibitory activity than letrozole. The rest of the tested compounds did not show significant inhibition, and it can be assumed that they exert their antiproliferative activity through different target mechanisms. In addition, caspase-9 protein activation assays, cell cycle analysis using flow cytometry, and annexin V-fluorescein isothiocyanate-propidium iodide (FITC/PI) dual staining assays were performed for the most active compounds. All the tested compounds were found to be potent pyrimidine derivatives able to initiate apoptosis in MCF-7 and MDA-MB-231 cells.

Synthesis, and reverse screening of 6‐(3,4,5‐trimethoxyphenyl)pyrimidine‐5‐carbonitrile derivatives as anticancer agents: Part‐II

“…Based on the reported literature [13] and our efforts devoted to the design and synthesis of cyanopyrimidine containing anticancer compounds, we have previously reported dihydropyrimidine-pyridazinone hybrids (1) with significant effect on breast cancer [14]. From the preliminary results obtained, we further designed cyanopyrimidine derivatives in which pyridazinone ring was replaced with methylene-bearing sulfur moiety in the form of isobutyl, isopropyl, and benzimidazole motif in addition to the " NH" or " N" placed at position ortho to the cyano group (2) based on the literature support [15,16].…”