Aim: The study aims to prepare a class of oleanolic-based compounds.
Background: Conventional drugs used to treat infectious diseases suffer from limitations
such as drug toxicity and drug resistance. The resistance of microbes to antimicrobial
agents is a significant challenge in treating microbial infections. Combining two or more
drugs with different modes of action to treat microbial infections results in a delay in developing
drug resistance by the microbes. However, it is challenging to select the appropriate
drugs for combination therapy due to the differences in stability and pharmacokinetic
profile of the drugs. Therefore, developing hybrid compounds using the existing
drugs is a promising approach to design effective antimicrobial agents.
Objectives: To prepare oleanolic-based hybrid compounds followed by characterization,
in vitro antibacterial and cytotoxicity evaluation.
Methods: Oleanolic acid-4-aminoquinoline-based hybrid compounds were synthesized
via esterification and amidation. The compounds were characterized using
FTIR, NMR, and UHPLC-HRMS. Oleanolic acid (OA) was isolated from the
flower buds of Syzygium aromaticum (L.) Merr. & L.M.Perry, a species from
Kingdom Plantae, order Mytales in the Myrtaceae family. Antibacterial activity
was determined against selected strains of bacteria using the microdilution assay
and cytotoxicity activity was assessed using the sulforhodamine B assay against
selected cancer cell lines.
Results: The synthesized hybrid compounds exhibited antibacterial activity against the
Gram-positive bacteria Enterococcus faecalis (ATCC13047), Bacillus subtilis (ATCC19659),
Staphylococcus aureus as well as Gram-negative bacteria, Klebsiella oxytoca
(ATCC8724), Escherischia coli (ATCC25922), and Proteus vulgaris (ATCC6380) with
minimum inhibitory concentrations of 1.25 mg/mL compared to oleanolic acid (2.5
mg/mL). Compounds 13 and 14 displayed cytotoxicity in vitro against the cancer cell
lines (MCF-7 and DU 145) compared to the oleanolic acid (IC50 ˃ 200 μM).
Conclusion: Modification of C28 of OA enhanced its biological activity.