Zhang, Xiaojie; Guo, Shanchun; Chen, Chengsheng; Perez, German Ruiz; Zhang, Changde; Patanapongpibul, Manee; Subrahmanyam, Nithya; Wang, Rubing; Keith, Joshua; Chen, Guanglin; Dong, Yan; Zhang, Qiang; Zhong, Qiu; Zheng, Shilong; Wang, Guangdi; Chen, Qiao-Hong published the artcile< Asymmetric 1,5-diarylpenta-1,4-dien-3-ones: Antiproliferative activity in prostate epithelial cell models and pharmacokinetic studies>, Quality Control of 112-63-0, the main research area is bisdiethylphosphonato acetone heteroaryl aldehyde diastereoselective Horner Wadsworth Emmons reaction; oxo heteroarylbutenyl phosphonate preparation aldehyde diastereoselective Horner Wadsworth Emmons; diheteroarylpentadienone preparation antitumor activity SAR apoptosis acute toxicity; 1,5-Diheteroarylpenta-1,4-dien-3-one; Cell apoptosis; Cell proliferation; Pharmacokinetic study; Prostate cancer.
To further engineer dienones with optimal combinations of potency and bioavailability, thirty-four asym. 1,5-diarylpenta-1,4-dien-3-ones I [R1 = 1-(sec-butyl)-1H-imidazol-2-yl, pyridin-2-yl, 1-isopropyl-1H-benzo[d]imidazol-2-yl, etc.; R2 = 3,4-dimethoxyphenyl, thiazol-2-yl, 2-(piperidin-1-yl)thiazol-5-yl, etc.] were designed and synthesized for the evaluation of their in vitro anti-proliferative activity in three human prostate cancer cell lines and one non-neoplastic prostate epithelial cell line. All these asym. dienones I were sufficiently more potent than curcumin and their corresponding sym. counterparts. The optimal dienone I [R1 = 1-isopropyl-1H-benzo[d]imidazol-2-yl; R2 = pyridin-2-yl], with IC50 values in the range of 0.03-0.12 μM, was 636-, 219-, and 454-fold more potent than curcumin in three prostate cancer cell models. Dienones I [R1 = 1-(sec-butyl)-1H-imidazol-2-yl (II), 1-ethyl-1H-benzo[d]imidazol-2-yl; R2 = 2-methyl-4-(trifluoromethyl)thiazol-5-yl] emerged as the most promising asym. dienones that warrant further preclin. studies. The two lead compounds demonstrated substantially improved potency in cell models and superior bioavailability in rats, while exhibiting no acute toxicity in the animals at the dose of 10 mg/kg. Dienones II and I [R1 = 1-propyl-1H-benzo[d]imidazole-2-yl, R2 = 1-propyl-1H-imidazole-2-yl (III)] could induce PC-3 cell cycle regulation at the G0/G1 phase. However, dienone II induced PC-3 cell death in a different way from III even though they share the same scaffold, indicating that terminal heteroaromatic rings were critical to the action of mechanism for each specific dienone.
European Journal of Medicinal Chemistry published new progress about Acute toxicity. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Quality Control of 112-63-0.
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