Betulinic Acid Fatty Esters and Their Liposomal Formulations: Targeting Cytotoxicity Against Ovarian, Colorectal, and Lung Cancer Cells
1 Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, 300041 Timișoara, Romania
2 Research Center for Experimental Pharmacology and Drug Design (X-Pharm Design), “Victor Babes” University of Medicine and Pharmacy, 300041 Timișoara, Romania
3 email:
* Author to whom correspondence should be addressed.
Received: 14 Jul 2025 / Accepted: 1 Jan 1970 / Published: 29 Jul 2025
Abstract
Despite its notable anticancer potential, betulinic acid (BA) exhibits limited bioavailability that hampers its therapeutic efficacy. To address this issue, betulinic acid fatty esters were previously synthesized by employing stearic (St-BA), palmitic (Pal-BA), and butyric acids (But-BA), and further incorporated into surface-modified liposomal formulations (St-BA-Lip, Pal-BA-Lip, But-BA-Lip). The BA derivatives, as well as their liposomal formulations, were assessed against three human cancer cell lines: colorectal adenocarcinoma Caco-2 cells, ovarian teratocarcinoma PA-1, and alveolar epithelial adenocarcinoma A549 cells. All compounds exhibited cytotoxic effects in a time- and dose-dependent manner, more potently than the positive control, 5-fluorouracil (5-FU). But-BA-Lip exhibited the best anticancer effects against all tested cancer cell lines, recording lower IC50 values than the parent compound (BA) and 5-FU (15.55 μM against Caco-2 cells, 48.16 μM against PA-1 cells, and 25.3 μM against A549 cells). In silico molecular docking studies revealed that Pal-BA showed superior binding affinity to AKT/PKB than the parent compound, BA, while But-BA showed enhanced interaction with EGFR1. Both derivatives achieved 93% of the native ligand’s docking score, highlighting their therapeutic potential through structural modifications.
Keywords: anticancer; liposomes; betulinic acid; triterpenes; fatty esters; cytotoxicity assay; molecular docking
OPEN ACCESS
This is an open access article distributed under the Creative Commons Attribution
License which permits unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly cited. (CC BY 4.0).
CITE
Milan, A.; Mioc, M.; Prodea, A.; Șoica, C. Betulinic Acid Fatty Esters and Their Liposomal Formulations: Targeting Cytotoxicity Against Ovarian, Colorectal, and Lung Cancer Cells. jept 2025, 2, 3.
Milan A, Mioc M, Prodea A, Șoica C. Betulinic Acid Fatty Esters and Their Liposomal Formulations: Targeting Cytotoxicity Against Ovarian, Colorectal, and Lung Cancer Cells. Journal of Experimental Pharmacology and Toxicology. 2025; 2(2):3.
Milan, Andreea; Mioc, Marius; Prodea, Alexandra; Șoica, Codruța. 2025. "Betulinic Acid Fatty Esters and Their Liposomal Formulations: Targeting Cytotoxicity Against Ovarian, Colorectal, and Lung Cancer Cells." jept 2, no. 2: 3.
Not implemented
SHARE
