Molecular docking and adme profiling of xanthorrhizol derivatives as hyaluronidase inhibitors

• Main Authors: Tengku Nazmi, Tengku Kamilah, Aminudin, Nurul Iman, Hamzah, Nurasyikin
• Format: Article
• Language: English
• Published: Malaysian Institute of Chemistry 2022
• Subjects: QD Chemistry
• Online Access: http://irep.iium.edu.my/98684/7/98684_Molecular%20docking%20and%20adme%20profiling.pdf; http://irep.iium.edu.my/98684/; https://ikm.org.my/publications/malaysian-journal-of-chemistry/current-issue.php
• Institution: Universiti Islam Antarabangsa Malaysia

Hyaluronidase (Hyal) enzyme is a potential biological target for the development of anti-inflammatory agents. Xanthorrhizol, a bisabolene sesquiterpenoid isolated from Curcuma xanthorrhiza has been reported to show anti-inflammatory activity against cyclooxygenase (COX), inducible nitric oxide synthase (iNOS), and interleukins (IL). However, the activity of xanthorrhizol as a Hyal inhibitor has not been exploited. In this study, a total of 26 xanthorrhizol derivatives with structural modifications at the R1 - R4 scaffold were chosen. Molecular docking was performed to virtually screen their structure-activity relationships towards Hyal, while ADME prediction was done to predict their pharmacokinetic profiles. All derivatives bound to the active site of Hyal1 with binding energies ranging from -5.7 kcal/mol to -8.5 kcal/mol. Derivatives 24 and 14 with a benzyloxy moiety at position R1 and polar moieties at positions R3 and R4 showed lower binding energies (-8.3, and -7.9 kcal/mol, respectively) compared to apigenin, 28 (-7.9 kcal/mol) and xanthorrhizol, 1 (-6.5 kcal/mol). These derivatives also fulfilled all ADME and drug-likeness properties, indicating they were potential Hyal inhibitors. Through this work, the activity of xanthorrhizol derivatives against Hyal1 may be predicted and screened as a basis for future modifications of xanthorrhizol to create a potential Hyal inhibitor.