ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Cytotoxicity-guided isolation of acacetin derivatives from Cirsium rhizocephalum C.A.Mey. (Asteraceae) and their in silico investigation for androgen receptor inhibition against prostate cancer

Aya Aygün, Feyza Kılınç, Alperen Samet Özmen, Merve Esra Bayram, Almina Nur Kiper, Kübra Uzun, Şengül Dilem Doğan, Miyase Gözde Gündüz, Ahmet Cumaoğlu, and Perihan Gürbüz

Pharmacy Undergraduate Program, Faculty of Pharmacy, Erciyes University, Kayseri, Türkiye

E-mail: perihan.eser@gmail.com

Received: 9 July 2024  Accepted: 1 June 2025

Abstract:

Bioactivity-guided investigation of Cirsium rhizocephalum against the human androgen-sensitive prostate cancer cell line (LnCAP) led to the isolation of six flavonoids: nicotiflorin (CRE_1), rutin (CRE_2), isoquercetin (CRE_4), linarin (CRE_5), acacetin (CRE_6a), 6-methoxy acacetin (CRE_6b), and chlorogenic acid (CRE_3). The chemical structures of the compounds were determined by examining their ¹H NMR spectra, comparing them with existing literature, and by authentication with thin-layer chromatography (TLC) for rutin and chlorogenic acid. To rationalize and support the obtained cytotoxicity data against human androgen-sensitive prostate cancer cells, purified molecules were docked into the binding site of the human androgen receptor (AR), a validated therapeutic target for the treatment of prostate cancer. In line with the biological results, the isolated flavones acacetin and 6-methoxy acacetin, with the strongest cytotoxic activity against prostate cancer cell lines, interacted with AR in a similar way to the native ligand, metribolone. The stability of the binding modes of both compounds within the active pocket of AR was confirmed by applying molecular dynamic simulations and the dynamic 3D pharmacophore (dynophore) method. Furthermore, the molecular descriptors indicating drug-likeness were calculated for all compounds isolated from C. rhizocephalum.

Keywords: Cirsium sp.; Flavonoid; Molecular modeling; Flavone; Cancer

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-025-04162-w

Chemical Papers 79 (9) 5911–5920 (2025)