Synthesis and in vitro evaluation of oleanolic acid derivatives with enhanced neuroprotective and cytotoxic activities
Bildiriler > Tam Metin Bildiri
Yazarlar: G S Okkalı, C G Hızlıateş, B Kaya, A Nalbantsoy, N Sarıkahya
Planta Medica, , , Uluslararası, Tam Metin Bildiri, Wos, cilt 92
Özet
Oleanolic acid, a naturally occurring triterpenoid compound, has garnered significant attention for its potential therapeutic benefits [ 1 ] [ 2 ]. In this study, oleanolic acid, isolated from Scabiosa pseudograminifolia, was used as the starting material for semisynthetic modifications to enhance neuroprotective activity and cytotoxic effects. Three derivatives were synthesized through amidation reactions employing 3-(1 H -tetrazol-5-yl)aniline (S1), 4-(1 H -tetrazol-5-yl)aniline (S2), and 4-bromobenzylamine (S3), with yields of 68% for S1, 72% for S2, and 56% for S3. The neuroprotective potential of these compounds was evaluated using the MTT assay on SH-SY5Y human neuroblastoma cells subjected to hydrogen peroxide-induced oxidative stress at concentrations of 0.5, 1, 5, 10, 50, and 100 μg/mL. At the lowest concentration (0.5 μg/mL; 0.83 μM for S1 and S2, 0.80 μM for S3), S3 exhibited the highest cell viability (133.88±2.47, P<0.0001), followed by S1 (121.70±2.60, P<0.0001) and S2 (112.14±1.65, P<0.001), while oleanolic acid showed 115.35±4.90 (P<0.0001). Similar trends were observed at 5 μg/mL and 50 μg/mL, with S3 consistently providing superior protection. In parallel, cytotoxicity was assessed on HEK-293 cells and various cancer cell lines (PC-3, A549, MDA-MB-231, PANC-1, SH-SY5Y) [ 3 ]. Notably, S2 demonstrated enhanced cytotoxic activity against A549, MDA-MB-231, and PANC-1 cells with IC 50 values of 57.21±4.40 μM, 131.78±6.83 µM, and 81.87±4.65 μM, respectively, compared to higher values for the parent compound. These findings indicate that structural modifications of oleanolic acid can improve both neuroprotective and cytotoxic profiles, warranting further mechanistic and in vivo investigations. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany