TY - JOUR
T1 - Design of Oleanolic Acid-based Hybrid Compounds as Potential Pharmaceutical Scaffolds
AU - Khwaza, Vuyolwethu
AU - Oyedeji, Opeoluwa Oyehan
AU - Aderibigbe, Blessing Atim
AU - Morifi, Eric
AU - Fonkui, Youmbi Thierry
AU - Ndinteh, Derek Tantoh
AU - Nell, Margo
AU - Steenkamp, Vanessa
N1 - Publisher Copyright:
© 2022 Bentham Science Publishers.
PY - 2022/1
Y1 - 2022/1
N2 - 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. Anti-bacterial 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.
AB - 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. Anti-bacterial 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.
KW - 4-aminosalicylic acid
KW - Antibacterial
KW - Anticancer
KW - Curcumin
KW - Hybrid compound
KW - Oleanolic acid
UR - http://www.scopus.com/inward/record.url?scp=85126101402&partnerID=8YFLogxK
U2 - 10.2174/1570180818666210604112451
DO - 10.2174/1570180818666210604112451
M3 - Article
AN - SCOPUS:85126101402
SN - 1570-1808
VL - 19
SP - 10
EP - 19
JO - Letters in Drug Design and Discovery
JF - Letters in Drug Design and Discovery
IS - 1
ER -
