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Title: Synthesis and molecular docking of N,N′-disubstituted thiourea derivatives as novel aromatase inhibitors
Authors: Ratchanok Pingaew
Veda Prachayasittikul
Nuttapat Anuwongcharoen
Supaluk Prachayasittikul
Somsak Ruchirawat
Virapong Prachayasittikul
South Carolina Commission on Higher Education
Chulabhorn Research Institute
Mahidol University
Srinakharinwirot University
Chulabhorn Graduate Institute
Keywords: Biochemistry, Genetics and Molecular Biology;Chemistry;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Sep-2018
Citation: Bioorganic Chemistry. Vol.79, (2018), 171-178
Abstract: © 2018 Elsevier Inc. A three series of thioureas, monothiourea type I (4a–g), 1,4-bisthiourea type II (5a–h) and 1,3-bisthiourea type III (6a–h) were synthesized. Their aromatase inhibitory activities have been evaluated. Interestingly, eight thiourea derivatives (4e, 5f–h, 6d, 6f–h) exhibited the aromatase inhibitory activities with IC50 range of 0.6–10.2 μM. The meta-bisthiourea bearing 4-NO2 group (6f) and 3,5-diCF3 groups (6h) were shown to be the most potent compounds with sub-micromolar IC50 values of 0.8 and 0.6 μM, respectively. Molecular docking also revealed that one of the thiourea moieties of these two compounds could mimic steroidal backbone of the natural androstenedione (ASD) via hydrophobic interactions with enzyme residues (Val370, Leu477, Thr310, and Phe221 for 6f, Val370, Leu477, Ser478, and Ile133 for 6h). This is the first time that the bisthioureas have been reported for their potential to be developed as aromatase inhibitors, in which the 4-NO2 and 3,5-diCF3 analogs have been highlighted as promising candidates.
ISSN: 10902120
Appears in Collections:Scopus 2018

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