Sesquiterpene coumarins, chromones, and acetophenone derivatives with selective cytotoxicities from the roots of ferula caspica m. bieb. (apiaceae)

Kuran, Fadıl Kaan; Altıparmak Ülbegi, Gülsüm; Arcan, Gülşah Gamze; Eruçar, Fatma Memnune; Karavuş, Şule Nur; Tan, Nur; Miski, Mahmut

Sesquiterpene coumarins, chromones, and acetophenone derivatives with selective cytotoxicities from the roots of ferula caspica m. bieb. (apiaceae)

dc.contributor.author	Kuran, Fadıl Kaan
dc.contributor.author	Altıparmak Ülbegi, Gülsüm
dc.contributor.author	Arcan, Gülşah Gamze
dc.contributor.author	Eruçar, Fatma Memnune
dc.contributor.author	Karavuş, Şule Nur
dc.contributor.author	Tan, Nur
dc.contributor.author	Miski, Mahmut
dc.date.accessioned	2025-10-20T13:19:55Z
dc.date.available	2025-10-20T13:19:55Z
dc.date.issued	2024
dc.department	İstanbul Medipol Üniversitesi, Eczacılık Fakültesi, Eczacılık Meslek Bilimleri Bölümü, Farmakognozi Ana Bilim Dalı
dc.description.abstract	In search of selective cytotoxic compounds from Ferula species as potential leads for the treatment of various cancer diseases, a bioactivity-guided isolation study was performed on the roots of Ferula caspica M. Bieb. COLO 205 (colon), K-562 (leukemia), and MCF-7 (breast) cancer cell lines were used to monitor the cytotoxic activity of column fractions and determine the IC50 value of the active compounds. In addition to the seven known (5–11) compounds, four previously unknown compounds: kayserin A (1), kayserin B (2), 8′-epi-kayserin B angelate (3), and 3-epi-ferulin D (4) were isolated from the dichloromethane extract of the roots of F. caspica. Structure elucidation of the isolated compounds was carried out by extensive spectroscopic analyses such as 1D- and 2D-NMR spectroscopy, High-Resolution Mass Spectroscopy (HRMS), IR spectroscopy, and UV spectroscopy. Although all of the isolated compounds showed various degrees of cytotoxic activity on COLO 205, K-562, and MCF-7 cancer cell lines, the most potent compounds were identified in the following order: 1-Hydroxy-1-(1′-farnesyl)-4,6-dihydroxyacetophenone (HFDHAP, 11), 3-epi-ferulin D (3EFD, 4), and 7-desmethylferulin D (7DMFD, 6). The cytotoxic activities of all three compounds were more potent than that of the reference compound cisplatin (Cis) against all tested cancer cell lines. Still, only HFDHAP (11) was more potent than the reference compound doxorubicin (Dox) against the MCF-7 cancer cell line. The mechanism of action of these three compounds was investigated on the COLO 205 cell line. The results indicated that compounds 4, 6, and 11 trigger caspase-3/8/9 activation and suppress the anti-apoptotic protein, Bcl-xL. Molecular docking studies confirmed the interactions of the three cytotoxic molecules with the active site of the Bcl-xL protein.
dc.description.sponsorship	Türkiye Bilimsel ve Teknolojik Araştırma Kurumu (TÜBİTAK) ; Scientific Research Projects Coordination Unit of Istanbul University, Turkiye
dc.identifier.citation	Kuran, F. K., Altıparmak Ülbegi, G., Arcan, G. G., Eruçar, F. M., Karavuş, Ş. N., Tan, N. ... Miski, M. (2024). Sesquiterpene coumarins, chromones, and acetophenone derivatives with selective cytotoxicities from the roots of ferula caspica m. bieb. (apiaceae). Pharmaceuticals, 17(10). http://dx.doi.org/10.3390/ph17101254
dc.identifier.doi	10.3390/ph17101254
dc.identifier.issn	1424-8247
dc.identifier.issue	10
dc.identifier.pmid	39458896
dc.identifier.scopus	2-s2.0-85207677074
dc.identifier.scopusquality	Q1
dc.identifier.uri	http://dx.doi.org/10.3390/ph17101254
dc.identifier.uri	https://hdl.handle.net/20.500.12511/13125
dc.identifier.volume	17
dc.identifier.wos	WOS:001343182200001
dc.identifier.wosquality	Q1
dc.indekslendigikaynak	Web of Science
dc.indekslendigikaynak	Scopus
dc.indekslendigikaynak	PubMed
dc.institutionauthor	Karavuş, Şule Nur
dc.institutionauthorid	0000-0001-9265-8042
dc.language.iso	en
dc.relation.ec	info:eu-repo/grantAgreement/EC/FP7/35861
dc.relation.ispartof	Pharmaceuticals
dc.relation.publicationcategory	Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.relation.tubitak	info:eu-repo/grantAgreement/TUBITAK/SOBAG/117S419
dc.rights	info:eu-repo/semantics/openAccess
dc.rights	Attribution 4.0 International
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/
dc.subject	Bcl-Xl
dc.subject	Caspase-3/8/9
dc.subject	COLO 205
dc.subject	Cytotoxicity
dc.subject	Ferula Caspica
dc.subject	K-562
dc.subject	MCF-7
dc.subject	Molecular Docking
dc.subject	Sesquiterpenes
dc.title	Sesquiterpene coumarins, chromones, and acetophenone derivatives with selective cytotoxicities from the roots of ferula caspica m. bieb. (apiaceae)
dc.type	Article