Design of oleanolic acid-based hybrid compounds as potential pharmaceutical scaffolds

dc.contributor.authorKhwaza, Vuyolwethu
dc.contributor.authorOyedeji, Opeoluwa Oyehan
dc.contributor.authorAderibigbe, Blessing Atim
dc.contributor.authorMorifi, Eric
dc.contributor.authorFonkui, Youmbi Thierry
dc.contributor.authorNdinteh, Derek Tantoh
dc.contributor.authorNell, Margo Judith
dc.contributor.authorSteenkamp, Vanessa
dc.date.accessioned2023-02-10T12:43:06Z
dc.date.available2023-02-10T12:43:06Z
dc.date.issued2022-01
dc.description.abstractBACKGROUND : 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.en_US
dc.description.departmentPharmacologyen_US
dc.description.librarianhj2023en_US
dc.description.sponsorshipThe South African Medical Research Council (Self-Initiated Research), National Research Foundation South African and Govan Mbeki Research and Development Centre (GMRDC), University of Fort Hare.en_US
dc.description.urihttps://benthamscience.com/journals/letters-in-drug-design-and-discoveryen_US
dc.identifier.citationKhwaza, V., Oyedeji, O.O., Aderibigbe, B.A. et al. 2022, 'Design of oleanolic acid-based hybrid compounds as potential pharmaceutical scaffolds', Letters in Drug Design and Discovery, vol. 19, no. 1, pp. 10-19, doi : 10.2174/1570180818666210604112451.en_US
dc.identifier.issn1570-1808 (print)
dc.identifier.issn1875-628X (online)
dc.identifier.other10.2174/1570180818666210604112451
dc.identifier.urihttps://repository.up.ac.za/handle/2263/89414
dc.language.isoenen_US
dc.publisherBentham Science Publishersen_US
dc.rights© 2021 Bentham Science Publishersen_US
dc.subject4-aminosalicylic aciden_US
dc.subjectOleanolic aciden_US
dc.subjectAntibacterialen_US
dc.subjectAnticanceren_US
dc.subjectCurcuminen_US
dc.subjectHybrid compoundsen_US
dc.titleDesign of oleanolic acid-based hybrid compounds as potential pharmaceutical scaffoldsen_US
dc.typePostprint Articleen_US

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