Abstract B016: Evaluation of the anti-breast cancer activity of isolates and semi-synthesized compounds from <i>Alstonia scholaris</i> leaves and <i>Psorospermum guineense</i> twigs

Abstract Breast cancer is the second most common cancer in women after lung cancer and a leading cause of death. Between 2010 and 2015, 6000 Cameroonian women died of cancer, and the breast is the most affected with 2625 new cases recorded. Treatment of breast cancer involves, amongst others, chemotherapy using tamoxifen. The treatment is costly, and resistance of tumor cells to the available antineoplastic drugs has exacerbated the cost. New families of active compounds are needed especially from natural sources in order to decrease the risk of resistance. The families, Hypericaceae and Apocynaceae and most especially the species Psorospermum guineense and Alstonia scholaris are used in traditional medicine to treat different illnesses such as malaria and cancer. These species are rich in secondary metabolities such as quinones, triterpenes and alkaloids but little information is known of the mode of action of these compounds in the treatment of cancer. The general objective of this work was to carry out phytochemical studies of the twigs of Psorospermum guineense and the leaves of Alstonia scholaris, structural modification of some isolated compounds, anti-breast cancer activity and molecular docking studies. By using chromatography, compounds were isolated from the 2 plants and their structures were determined by interpretation of their spectroscopic and spectrometric spectra. Cytotoxicity was determined through cells plated in 96 - well plates. The synthesis was carried out using SeO2. The phytochemical study of the leaves of A. scholaris resulted in the isolation and characterization of 9 compounds, namely: betulin, α-amyrin acetate, mixture of β-sitosterol and stigmasterol, tetratriacontyl-trans-p-coumarate, ursolic acid, β-sitosterol glucoside, picralstonine and scholaricine. Meanwhile, we got 8 compounds from the twigs of P. guineense namely; 3-geranyloxyemodin, 3-β-fridelanol, 3-geranyloxyemodin anthrone, 2- geranylemodin, acetylvismione D, betulinic acid, ursolic acid and emodin. Betulin afforded betulin acrylaldehyde while α-amyrin acetate afforded lupeol acetate acrylaldehyde in an intriguing mechanism with the conversion of ursane to lupane scaffold. Preliminary cytotoxicity assays of the isolated and synthesized compounds was carried out against the triple negative (MDA-MB-231) breast cancer cell and the results indicated that Ursolic acid was the most active amongst the isolated compounds, with an IC50 value of 9.88 μM and 95 % CI of 9.03-10.5 μM. On the other hand, the transformed compound, lupeol acetate acryl aldehyde with the privilege α, β-unsaturated carbonyl scaffold showed an increase in activity against MDA MB 231 breast cancer cell lines with an IC50 of 4.63 ± 0.09 μg/ml. Further studies may lead to the development of new therapeutic agents. Citation Format: Eyong Kenneth Oben, Ghansenyuy Salome Yuwong, Yemback Pierre, Muhammad Ali Shaiq. Evaluation of the anti-breast cancer activity of isolates and semi-synthesized compounds from Alstonia scholaris leaves and Psorospermum guineense twigs [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Mechanisms of Cancer Immunity and Cancer-related Autoimmunity; 2025 Sep 24-27; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(9 Suppl):Abstract nr B016.