2. Academic Validation
  3. Synthesis, molecular docking, and QSAR study of bis-sulfonamide derivatives as potential aromatase inhibitors

Synthesis, molecular docking, and QSAR study of bis-sulfonamide derivatives as potential aromatase inhibitors

  • Bioorg Med Chem. 2019 Oct 1;27(19):115040. doi: 10.1016/j.bmc.2019.08.001.
Ronnakorn Leechaisit 1,  Ratchanok Pingaew 2,  Veda Prachayasittikul 3,  Apilak Worachartcheewan 4,  Supaluk Prachayasittikul 5,  Somsak Ruchirawat 6,  Virapong Prachayasittikul 7
Affiliations

Affiliations

  • 1 Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand.
  • 2 Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand. Electronic address: ratchanok@swu.ac.th.
  • 3 Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand. Electronic address: veda.pra@mahidol.ac.th.
  • 4 Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand; Department of Community Medical Technology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand; Department of Clinical Chemistry, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
  • 5 Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
  • 6 Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, and Program in Chemical Biology, Chulabhorn Graduate Institute, Bangkok 10210,Thailand; Center of Excellence on Environmental Health and Toxicology, Commission on Higher Education (CHE), Ministry of Education, Thailand.
  • 7 Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
PMID: 31416738 DOI: 10.1016/j.bmc.2019.08.001
Abstract

A library of bis-sulfonamides (9-26) were synthesized and tested for their aromatase inhibitory activities. Interestingly, all bis-sulfonamide derivatives inhibited the aromatase with IC50 range of 0.05-11.6 μM except for compound 23. The analogs 15 and 16 bearing hydrophobic chloro and bromo groups exhibited the potent aromatase inhibitory activity in sub-micromolar IC50 values (i.e., 50 and 60 nM, respectively) with high safety index. Molecular docking revealed that the chloro and bromo benzenesulfonamides (15 and 16) may play role in the hydrophobic interaction with Leu477 of the aromatase to mimic steroidal backbone of the natural substrate, androstenedione. QSAR study also revealed that the most potent activity of compounds was governed by van der Waals volume (GATS6v) and mass (Mor03m) descriptors. Finally, the two compounds (15 and 16) were highlighted as promising compounds to be further developed as novel aromatase inhibitors.

Keywords

Aromatase inhibitor; Bis-sulfonamide; Molecular docking; QSAR; Sulfonamide; Xylylenediamine.

Figures