149487-05-8Relevant articles and documents
Design, synthesis, and computational validation of novel compounds selectively targeting HER2-expressing breast cancer
Elseginy, Samia A.,Hamdy, Rania,Menon, Varsha,Almehdi, Ahmed M.,El-Awady, Raafat,Soliman, Sameh S.M.
, (2020/11/09)
Human epidermal growth factor receptor (HER) is a family of multidomain proteins that plays important role in the regulation of several biological functions. HER2 is a member of HER that is highly presented in breast cancer cells. Here, we designed and synthesized a series of diaryl urea/thiourea compounds. The compounds were tested on HER2+ breast cancer cells including MCF-7 and SkBr3, compared to HER2- breast cancer cells including MDA-MB-231 and BT-549. Only compounds 12–14 at 10 μM showed selective anti-proliferative activity against MCF-7 and SkBr3 by 65–79%. Compounds 12–14 showed >80% inhibition of the intracellular kinase domain of HER2. The results obtained indicated that compounds 12–14 are selectively targeting HER2+ cells. The IC50 of compound 13 against MCF-7 and SkBR3 were 1.3 ± 0.009 and 0.73 ± 0.03 μM, respectively. Molecular docking and MD simulations (50 ns) were carried out, and their binding free energies were calculated. Compounds 12–14 formed strong hydrogen bond and pi–pi stacking interactions with the key residues Thr862 and Phe864. 3DQSAR model confirmed the role of 3-bromo substituent of pyridine ring and 4-chloro substituent of phenyl ring in the activity of the compounds. In conclusion, novel compounds, particularly 13 were developed selectively against HER2-expressing/overexpressing breast cancer cells including MCF7 and SkBr3.
Phenethylthiazolethiourea (PETT) compounds, a new class of HIV-1 reverse transcriptase inhibitors. 1. Synthesis and basic structure-activity relationship studies of PETT analogs
Bell,Cantrell,Hogberg,Jaskunas,Johansson,Jordan,Kinnick,Lind,Morin Jr.,Noreen,Oberg,Palkowitz,Parrish,Pranc,Sahlberg,Ternansky,Vasileff,Vrang,West,et al.
, p. 4929 - 4936 (2007/10/03)
A novel series of potent specific HIV-1 inhibitory compounds is described. The lead compound in the series, N-(2-phenethyl)-N'-(2-thiazolyl)thiourea (1), inhibits HIV-1 RT using rCdG as the template with an IC50 of 0.9 μM. In MT-4 cells, compound 1 inhibits HIV-1 with an ED50 of 1.3 μM. The 50% cytotoxic dose in cell culture is >380 μM. The chemical structure-activity relationship (SAR) was developed by notionally dividing the lead compound in four quadrants. The SAR strategy had two phases. The first phase involved optimization of antiviral activity through independent variation of quadrants 1-4. The second phase involved the preparation of hybrid structures combining the best of these substituents. Further SAR studies and pharmacokinetic considerations led to the identification of N-(2-pyridyl)-N'-(5-bromo-2- pyridyl)-thiourea (62; LY300046 · HCl) as a candidate for clinical evaluation. LY300046 · HCl inhibits HIV-1 RT with an IC50 of 15 nM and in cell culture has an ED50 of 20 nM.
