Design of Oleanolic Acid-based Hybrid Compounds as Potential Pharmaceutical
Scaffolds

Vuyolwethu       Khwaza; Opeoluwa    Oyehan    Oyedeji; Blessing    Atim    Aderibigbe; Eric       Morifi; Youmbi    Thierry    Fonkui; Derek    Tantoh    Ndinteh; Margo       Nell; Vanessa       Steenkamp

doi:10.2174/1570180818666210604112451

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.

Keywords: Oleanolic acid, anticancer, antibacterial, hybrid compound, 4-aminosalicylic acid, curcumin.

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