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Cytotoxic naphthoquinones from Arnebia densiflora (Nordm.) Ledeb and determining new apoptosis inducers
Authors:Merve Yuzbasioglu Baran  Zuhal Guvenalp  Iclal Saracoglu  Cavit Kazaz  Bekir Salih  L Omur Demirezer
Institution:1. Department of Pharmacognosy, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey;2. Department of Pharmacognosy, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey;3. Department of Chemistry, Faculty of Sciences, Ataturk University, Erzurum, Turkey;4. Department of Chemistry, Faculty of Science, Hacettepe University, Ankara, Turkey
Abstract:Abstract

In this study, phytochemical composition of Arnebia densiflora (AD) was determined and cytotoxic effects of the n-hexane extract and compounds isolated from this species on various cell lines were investigated. By means of serial chromatographic studies, 6 naphthoquinone derivatives were yielded, which are isovalerylalkannin, α-methyl-n-butyl alkannin, acetylalkannin, β-acetoxy isovalerylalkannin, alkannin and a new compound: 4-hydroxy 4-methyl valeryl alkannin. Structures of the isolated compounds were elucidated using UV, IR, 1D-2D NMR, MS and CD methods. Cytotoxic effects of the extract and isolated alkannins were investigated on L929, HeLa, HEp-2 cells. AD and the isolated compounds demonstrated moderate to strong cytotoxic effects (IC50 range: 4.92-172.35?µg/ml). The results of DNA fragmentation and caspase-3 activity studies on HeLa cells exhibited that AD and the naphthoquinones isolated from it caused cytotoxicity through induction of apoptosis.

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Keywords:Alkannin  cytotoxicity  caspase  apoptosis  Arnebia densiflora  Boraginaceae
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