Title:Design of Oleanolic Acid-based Hybrid Compounds as Potential Pharmaceutical
Scaffolds
Volume: 19
Issue: 1
Author(s): Vuyolwethu Khwaza, Opeoluwa Oyehan Oyedeji, Blessing Atim Aderibigbe*, Eric Morifi, Youmbi Thierry Fonkui, Derek Tantoh Ndinteh, Margo Nell and Vanessa Steenkamp
Affiliation:
- Department of Chemistry, Faculty of Science and Agriculture, University of Fort Hare, Alice Campus, Alice, Eastern
Cape, South Africa
Keywords:
Oleanolic acid, anticancer, antibacterial, hybrid compound, 4-aminosalicylic acid, curcumin.
Abstract:
Background: Infectious diseases, as well as cancer, are the leading causes of death
worldwide. Drug resistance usually results in their treatment requiring a combination of two or more
drugs.
Objective: Oleanolic-based hybrid compounds were prepared via esterification and characterized
using FTIR, NMR and LC-MS. In vitro antibacterial and in vitro cytotoxicity studies were performed.
Methods: Oleanolic acid was hybridized with selected known pharmaceutical scaffolds via the carboxylic
acid functionality in order to develop therapeutics with increased biological activity. Antibacterial
activity was determined using the micro-dilution assay against selected Gram-positive and
Gram-negative bacteria and cytotoxicity using the sulforhodamine B assay.
Results: Compound 8 displayed potent antibacterial effect against five strains of bacteria, such as
Bacillus subtilis, Staphylococcus aureus, Proteus vulgaris, Klebsiella oxytoca, and Escherichia coli,
with MIC values of 1.25, 0.078, 0.078, 1.25, 1.25 mg/mL when compared to the control, oleanolic
acid (MIC = 2.5 mg/mL). Furthermore, in vitro cytotoxicity, as determined using the SRB assay,
against selected cancer cells revealed that compound 7 was the most cytotoxic on MDA, DU145, and
MCF-7 cell lines with IC50 values of 69.87 ± 1.04, 73.2 ± 1.08, and 85.27 ± 1.02 μg/mL, respectively,
compared to oleanolic acid with an IC50 > 200 μg/mL.
Conclusion: Hybridization of oleanolic acid was successful, and further development of these potential
antibacterial compounds with reduced cytotoxicity is therefore warranted.