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

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. Method: Oleanolic acid was hybridized with selected known pharmaceutical scaffolds via the carboxylic acid functionality 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 to 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, than oleanolic acid with an IC50 ˃200 µg/mL. Conclusion: Hybridization of oleanolic acids was successful, and further development of these potential antibacterial compounds with reduced cytotoxicity is warranted.

Synthesis, Cytotoxicity and Molecular Docking of New Hybrid Compounds by Combination of Curcumin with Oleanolic Acid

“…The cytotoxicity of the studied compounds was assessed on a broad spectrum of mentioned cell lines using the MTT test. The assay was performed as previously described [ 34 ]. Briefly, a total of 5 × 10 3 cells were seeded into each well of 96-well plates in a total medium volume of 100 μL/well.…”

“…we find several pyrimidino-, pyridazino-and curcumin-steroid derivatives; cytotoxic effects versus human breast cancer cells (MCF7) [33] were shown; and potent antibacterial hybrid compounds containing oleanolic acid and curcumin [34].…”

“…We also synthesized and described the linked triterpene-phenolic hybrids and their molecular parameters, and the preliminary anti-inflammatory and antinociceptive activity characterizing these molecules as potential drugs were calculated and predicted [ 32 ]. In the literature, we find several pyrimidino-, pyridazino- and curcumin-steroid derivatives; cytotoxic effects versus human breast cancer cells (MCF7) [ 33 ] were shown; and potent antibacterial hybrid compounds containing oleanolic acid and curcumin [ 34 ].…”