Publication: Synthesis and molecular docking of N,N′-disubstituted thiourea derivatives as novel aromatase inhibitors
1
Issued Date
2018-09-01
Resource Type
ISSN
10902120
00452068
00452068
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2-s2.0-85046814081
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Mahidol University
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SCOPUS
Bibliographic Citation
Bioorganic Chemistry. Vol.79, (2018), 171-178
Suggested Citation
Ratchanok Pingaew, Veda Prachayasittikul, Nuttapat Anuwongcharoen, Supaluk Prachayasittikul, Somsak Ruchirawat, Virapong Prachayasittikul Synthesis and molecular docking of N,N′-disubstituted thiourea derivatives as novel aromatase inhibitors. Bioorganic Chemistry. Vol.79, (2018), 171-178. doi:10.1016/j.bioorg.2018.05.002 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/45069
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Title
Synthesis and molecular docking of N,N′-disubstituted thiourea derivatives as novel aromatase inhibitors
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.