Synthesis of Ursolic Acid-based Hybrids: In Vitro Antibacterial, Cytotoxicity Studies, In Silico Physicochemical and Pharmacokinetic Properties

Vuyolwethu Khwaza; S O Oselusi; Eric Morifi; M Nwamadi; Kamogelo S Hlope; D T Ndinteh; Thabe M Matsebatlela; Opeoluwa O Oyedeji; Blessing A Aderibigbe

doi:10.2174/0127724344272444231114103144

Synthesis of Ursolic Acid-based Hybrids: In Vitro Antibacterial, Cytotoxicity Studies, In Silico Physicochemical and Pharmacokinetic Properties

Recent Adv Antiinfect Drug Discov. 2024 Jan 2. doi: 10.2174/0127724344272444231114103144. Online ahead of print.

Authors

Vuyolwethu Khwaza¹, S O Oselusi², Eric Morifi³, M Nwamadi⁴, Kamogelo S Hlope⁵, D T Ndinteh⁶, Thabe M Matsebatlela⁵, Opeoluwa O Oyedeji¹, Blessing A Aderibigbe¹

Affiliations

¹ Department of Chemistry, University of Fort Hare, Alice Campus, Alice, Eastern Cape, South Africa.
² School of Pharmacy, University of the Western Cape, Bellville, Cape Town 7535, South Africa.
³ School of Chemistry, Mass Spectrometry Division, University of Witwatersrand, Johannesburg, South Africa.
⁴ Department of Chemistry, University of Johannesburg, Auckland Park Campus, Johannesburg, South Africa.
⁵ Department of Biochemistry, Microbiology and Biotechnology, Faculty of Science and Agriculture, University of Limpopo, South Africa.
⁶ Department of Applied Chemistry, University of Johannesburg, Doornfontein Campus, Johannesburg, South Africa.

PMID: 38317466
DOI: 10.2174/0127724344272444231114103144

Abstract

Background: There is a critical need for the discovery of novel and effective antibacterial or anticancer molecules.

Objectives: Amine-linked ursolic acid-based hybrid compounds were prepared in good yields in the range of 60-68%.

Methods: Their molecular structures were successfully confirmed using different spectroscopic methods including 1H/13C NMR, UHPLC-HRMS and FTIR spectroscopy. The in vitro cytotoxicity of some of these hybrid molecules against three human tumour cells, such as MDA-MB23, MCF7, and HeLa was evaluated using the MTT colorimetric method.

Result: Their antibacterial efficacy was evaluated against eleven bacterial pathogens using a serial dilution assay. Majority of the bacterial strains were inhibited significantly by compounds 17 and 24, with the lowest MIC values in the range of 15.3-31.25 μg/mL. Compound 16 exhibited higher cytotoxicity against HeLa cells than ursolic acid, with an IC50 value of 43.64 g/mL.

Conclusion: The in vitro antibacterial activity and cytotoxicity of these hybrid compounds demonstrated that ursolic acid-based hybrid molecules are promising compounds. Further research into ursolic acid-based hybrid compounds is required.

Keywords: Synthesis; antibacterial; anticancer; cytotoxicity; hybrid molecules; ursolic acid.