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

Overview

Journal Recent Adv Antiinfect Drug Discov

Specialties Infectious Diseases
Pharmacology

Date 2024 Feb 6

PMID 38317466

Authors

Vuyolwethu Khwaza

Samson Olaitan Oselusi

Eric Morifi

Mutshinyalo Nwamadi

Kamogelo S Hlope

Derek Tantoh Ndinteh

Thabe Moses Matsebatlela

Opeoluwa Oyehan Oyedeji

Blessing Atim Aderibigbe

Affiliations

Soon will be listed here.

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 H/C NMR, UHPLC-HRMS and FTIR spectroscopy. The 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 IC 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.

References

Xu B, Chu F, Zhang Y, Wang X, Li Q, Liu W . A Series of New Ligustrazine-Triterpenes Derivatives as Anti-Tumor Agents: Design, Synthesis, and Biological Evaluation. Int J Mol Sci. 2015; 16(9):21035-55. PMC: 4613240. DOI: 10.3390/ijms160921035. View

Khwaza V, Oyedeji O, Aderibigbe B . Ursolic Acid-Based Derivatives as Potential Anti-Cancer Agents: An Update. Int J Mol Sci. 2020; 21(16). PMC: 7460570. DOI: 10.3390/ijms21165920. View

Xiao S, Wang Q, Si L, Shi Y, Wang H, Yu F . Synthesis and anti-HCV entry activity studies of β-cyclodextrin-pentacyclic triterpene conjugates. ChemMedChem. 2014; 9(5):1060-70. DOI: 10.1002/cmdc.201300545. View

Sathya S, Sudhagar S, SarathKumar B, Lakshmi B . EGFR inhibition by pentacyclic triterpenes exhibit cell cycle and growth arrest in breast cancer cells. Life Sci. 2013; 95(1):53-62. DOI: 10.1016/j.lfs.2013.11.019. View

Shanmugam M, Dai X, Kumar A, Tan B, Sethi G, Bishayee A . Ursolic acid in cancer prevention and treatment: molecular targets, pharmacokinetics and clinical studies. Biochem Pharmacol. 2013; 85(11):1579-87. DOI: 10.1016/j.bcp.2013.03.006. View

Kazmi I, Rahman M, Afzal M, Gupta G, Saleem S, Afzal O . Anti-diabetic potential of ursolic acid stearoyl glucoside: a new triterpenic gycosidic ester from Lantana camara. Fitoterapia. 2011; 83(1):142-6. DOI: 10.1016/j.fitote.2011.10.004. View

Zhao J, Zheng H, Sui Z, Jing F, Quan X, Zhao W . Ursolic acid exhibits anti-inflammatory effects through blocking TLR4-MyD88 pathway mediated by autophagy. Cytokine. 2019; 123:154726. DOI: 10.1016/j.cyto.2019.05.013. View

Tohme M, Gimenez M, Peralta A, Colombo M, Delgui L . Ursolic acid: A novel antiviral compound inhibiting rotavirus infection in vitro. Int J Antimicrob Agents. 2019; 54(5):601-609. DOI: 10.1016/j.ijantimicag.2019.07.015. View

Ramachandran S, Prasad N . Effect of ursolic acid, a triterpenoid antioxidant, on ultraviolet-B radiation-induced cytotoxicity, lipid peroxidation and DNA damage in human lymphocytes. Chem Biol Interact. 2008; 176(2-3):99-107. DOI: 10.1016/j.cbi.2008.08.010. View

10.

Liu M, Yang S, Jin L, Hu D, Xue W, Song B . Synthesis and cytotoxicity of novel ursolic acid derivatives containing an acyl piperazine moiety. Eur J Med Chem. 2012; 58:128-35. DOI: 10.1016/j.ejmech.2012.08.048. View

11.

Rashid S, Dar B, Majeed R, Hamid A, Bhat B . Synthesis and biological evaluation of ursolic acid-triazolyl derivatives as potential anti-cancer agents. Eur J Med Chem. 2013; 66:238-45. DOI: 10.1016/j.ejmech.2013.05.029. View

12.

Gazivoda Kraljevic T, Harej A, Sedic M, Kraljevic Pavelic S, Stepanic V, Drenjancevic D . Synthesis, in vitro anticancer and antibacterial activities and in silico studies of new 4-substituted 1,2,3-triazole-coumarin hybrids. Eur J Med Chem. 2016; 124:794-808. DOI: 10.1016/j.ejmech.2016.08.062. View

13.

Yusuf K, Sampath V, Umar S . Bacterial Infections and Cancer: Exploring This Association And Its Implications for Cancer Patients. Int J Mol Sci. 2023; 24(4). PMC: 9958598. DOI: 10.3390/ijms24043110. View

14.

Gatadi S, Gour J, Nanduri S . Natural product derived promising anti-MRSA drug leads: A review. Bioorg Med Chem. 2019; 27(17):3760-3774. DOI: 10.1016/j.bmc.2019.07.023. View

15.

Rea F, Corrao G, Merlino L, Mancia G . Early cardiovascular protection by initial two-drug fixed-dose combination treatment vs. monotherapy in hypertension. Eur Heart J. 2018; 39(40):3654-3661. DOI: 10.1093/eurheartj/ehy420. View

16.

Wang P, Wang J, Guo T, Li Y . Synthesis and cytotoxic activity of the N-acetylglucosamine-bearing triterpenoid saponins. Carbohydr Res. 2010; 345(5):607-20. DOI: 10.1016/j.carres.2010.01.002. View

17.

Jin I, Ko Y, Kim Y, Han S . Solubilization of oleanolic acid and ursolic acid by cosolvency. Arch Pharm Res. 1997; 20(3):269-74. DOI: 10.1007/BF02976156. View

18.

Anusionwu C, Aderibigbe B, Adeyemi S, Ubanako P, Oselusi S, Choonara Y . Novel ferrocenylbisphosphonate hybrid compounds: Synthesis, characterization and potent activity against cancer cell lines. Bioorg Med Chem. 2022; 58:116652. DOI: 10.1016/j.bmc.2022.116652. View

19.

Bai K, Yu Z, Chen F, Li F, Li W, Guo Y . Synthesis and evaluation of ursolic acid derivatives as potent cytotoxic agents. Bioorg Med Chem Lett. 2012; 22(7):2488-93. DOI: 10.1016/j.bmcl.2012.02.009. View

20.

Pushpakom S, Iorio F, Eyers P, Jane Escott K, Hopper S, Wells A . Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov. 2018; 18(1):41-58. DOI: 10.1038/nrd.2018.168. View