Affiliations 

  • 1 Natural Product Division, Forest Research Institute Malaysia, 52109 Kepong, Malaysia. norhayatiab@frim.gov.my
  • 2 Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia. noelfthomas@um.edu.my
  • 3 Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia. yasodha@um.edu.my
  • 4 Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia. vannajan@um.edu.my
  • 5 Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia. joeyliew5382@um.edu.my
  • 6 BioProcess and Molecular Engineering Research Unit (BPMERU), Department of Biotechnology Engineering, Faculty of Engineering, International Islamic University Malaysia, 53100 Kuala Lumpur, Malaysia. ibrahiman@iium.edu.my
  • 7 Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia. khalijah@um.edu.my
Int J Mol Sci, 2016 Feb 14;17(2):143.
PMID: 26907251 DOI: 10.3390/ijms17020143

Abstract

The mammalian hyaluronidase degrades hyaluronic acid by the cleavage of the β-1,4-glycosidic bond furnishing a tetrasaccharide molecule as the main product which is a highly angiogenic and potent inducer of inflammatory cytokines. Ursolic acid 1, isolated from Prismatomeris tetrandra, was identified as having the potential to develop inhibitors of hyaluronidase. A series of ursolic acid analogues were either synthesized via structure modification of ursolic acid 1 or commercially obtained. The evaluation of the inhibitory activity of these compounds on the hyaluronidase enzyme was conducted. Several structural, topological and quantum chemical descriptors for these compounds were calculated using semi empirical quantum chemical methods. A quantitative structure activity relationship study (QSAR) was performed to correlate these descriptors with the hyaluronidase inhibitory activity. The statistical characteristics provided by the best multi linear model (BML) (R² = 0.9717, R²cv = 0.9506) indicated satisfactory stability and predictive ability of the developed model. The in silico molecular docking study which was used to determine the binding interactions revealed that the ursolic acid analog 22 had a strong affinity towards human hyaluronidase.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.