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. 2023 May 14;16(5):746.
doi: 10.3390/ph16050746.

The Effect of Oleanolic Acid and Its Four New Semisynthetic Derivatives on Human MeWo and A375 Melanoma Cell Lines

Barbara Bednarczyk-Cwynar  1 , Anna Leśków  2 , Izabela Szczuka  3 , Lucjusz Zaprutko  1 , Dorota Diakowska  2
Affiliations

The Effect of Oleanolic Acid and Its Four New Semisynthetic Derivatives on Human MeWo and A375 Melanoma Cell Lines

Barbara Bednarczyk-Cwynar et al. Pharmaceuticals (Basel). .

Abstract

This study aimed to synthesize four new semisynthetic derivatives of natural oleanolic acid (OA) and, based on an analysis of their cytotoxic and anti-proliferative effects against human MeWo and A375 melanoma cell lines, select those with anti-cancer potential. We also screened the treatment time with the concentration of all four derivatives. We synthesized oxime 2 and performed its acylation with carboxylic acids into new derivatives 3a, 3b, 3c and 3d according to the methods previously described. Colorimetric MTT and SRB assays were used to measure the anti-proliferative and cytotoxic activity of OA and its derivatives 3a, 3b, 3c and 3d against melanoma cells. Selected concentrations of OA, the derivatives, and different time periods of incubation were used in the study. The data were analyzed statistically. The present results revealed the possible anti-proliferative and cytotoxic potential of two selected OA derivatives 3a and 3b, on A375 and MeWo melanoma cells, especially at concentrations of 50 μM and 100 μM at 48 h of incubation (p < 0.05). Further studies will be necessary to analyze the proapoptotic and anti-cancer activities of 3a and 3b against skin and other cancer cells. The bromoacetoxyimine derivative (3b) of OA morpholide turned out to be the most effective against the tested cancer cells.

Keywords: cytotoxicity; human melanoma; oleanolic acid derivatives; triterpenes.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The synthesis procedure of anticancer agents. OA (1), oxime (2), acylated oximes of OA morpholide (3a–3d). i: Jones reagent, acetone, rt.; ii: (COCl2), rt.; morpholine, benzene, rt.; iii: NH2OH x HCl, CH3COONa, ethanol, reflux, iv: dioxane, DCC, (Ar)RCOOH, rt.
Figure 2
Figure 2
The results of the MTT assay (the metabolic activity test) on the viability of MeWo cells incubated with triterpenes OA, 3a, 3b, 3c, or 3d for (A) 6 h, (B) 24 h or (C) 48 h. Descriptive data were presented as mean ± SD. Statistically significant differences versus control cells were marked with an asterisk (* p ≤ 0.05). The horizontal bold line represents the viability of control (untreated) cells.
Figure 3
Figure 3
The results of the SRB assay (the cell number test) on the viability of MeWo cells incubated with triterpenes OA, 3a, 3b, 3c, or 3d for (A) 6 h, (B) 24 h or (C) 48 h. Descriptive data were presented as mean ± SD. Statistically significant differences versus control cells were marked with an asterisk (* p ≤ 0.05). The horizontal bold line represents the viability of control (untreated) cells.
Figure 4
Figure 4
The results of the MTT assay (the metabolic activity test) on the viability of A375 cells incubated with triterpenes OA, 3a, 3b, 3c, or 3d for (A) 6 h, (B) 24 h or (C) 48 h. Descriptive data were presented as mean ± SD. Statistically significant differences versus control cells were marked with an asterisk (* p ≤ 0.05). The horizontal bold line represents the viability of control (untreated) cells.
Figure 5
Figure 5
The results of the SRB assay (the cell number test) on the viability of A375 cells incubated with triterpenes OA, 3a, 3b, 3c, or 3d for (A) 6 h, (B) 24 h or (C) 48 h. Descriptive data were presented as mean ± SD. Statistically significant differences versus control cells were marked with an asterisk (* p < 0.05). The horizontal bold line represents the viability of control (untreated) cells.
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