Chemistry and Biological Activities of Naphthoquinones from Alkanna cappadocica Boiss.& Bal
Makaleler > Tam Makale · 2009
Yazarlar: C Sevimli-Gür, Kemal Sami KORKMAZ, İH Akgün, İ Deliloğlu-Gürhan, E Bedir
Planta Medica, Uluslararası, Wos, 2009, cilt 75
Özet
In a continuing program to discover new anticancer agents from plants, especially naphthoquinones from Alkanna genus, Alkanna cappadocica Boiss.&Bal was investigated [1]. Bioassay-guided fractionation of dichloromethane: methanol (1:1) extract of the roots led to the isolation of four new and four known naphthoquinones. Known compounds deoxyalkannin ( 1 ), β,β-dimethylacrylalkannin ( 2 ), acetylalkannin ( 3 ) and alkannin ( 4 ) [2,3], and new compounds, 5-methoxydeoxyalkannin ( 5 ), 8-methoxydeoxyalkannin ( 6 ), 5-methoxyacetylalkannin ( 7 ), 5-methoxy-β,β-dimethylacrylalkannin ( 8 ) were fully characterized by spectroscopic analyses (LC-ESI-MS, 1D- and 2D-NMR). Cytotoxicity of the isolated compounds was evaluated versus four human cancer cell lines HT-29, MDA-MB-231, PC-3, LNCaP, together with a normal cell line 3T3 by using MTT assay. Compounds 1, 2, 4, 7 and 8 showed remarkable cytotoxic activity against HT-29, MDA-MB-231 and PC-3 cell lines, comparable or stronger than the other compounds and positive control CPT-11 (CAMPTOSTAR®, irinotecan) with IC 50 values in between 0.1µM and 1µM. In order to confirm mechanism of action through DNA topoisomerase I inhibition which is a common feature for naphthoquinones, the compounds were incubated with topoisomerase I (topo I) and supercoiled DNA. These studies revealed that β,β-dimethylacrylalkannin ( 2 ) and acetylalkannin ( 3 ) have great potential as topo I inhibitors compared to other compounds and CPT-11, with 2–3µM inhibition value. Acknowledgement: This study was supported by Turkish Scientific and Technological Research Council of Turkey (Project No: SBAG-3134) . References: [1] Davis, P.H. (1978) „Flora of Turkey and East Aegean Islands“ Vol.3, University Press: Edinburgh. [2] Papageorgiou, V.P. et al. (1999) Angew. Chem. Int. Ed. 38:270–300. [3] Kourounakis, A.P. et al. (2002) Arch. Pharm. 335:262–266.