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A tormentic acid-homopiperazine-rhodamine B conjugate of single-digit nanomolar cytotoxicity and high selectivity for several human tumor cell lines
oleh: Oliver Kraft, Sophie Hoenke, René Csuk
Format: | Article |
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Diterbitkan: | Elsevier 2022-08-01 |
Deskripsi
Tormentic acid and euscaphic acid were isolated from plant material and transformed into amides holding an extra rhodamine B moiety; these compounds were screened for their cytotoxic activity employing a panel of human tumor cell lines and non-malignant fibroblasts. Prerequisites for both high cytotoxicity and tumor cell selectivity seem to be the combination of an amide (from a secondary amine but not from a primary), the use of homopiperazine rather than piperazine as a spacer together with rhodamine B (as a cationic center) and – most important-a triterpene holding a (2α, 3β) configuration of the substituents in ring A of the triterpenoid skeleton. All these features are found in tormentic acid derived compound 15; it acts as a mitocan; it is approximately 190 times more cytotoxic for ovarian carcinoma cells than for non-malignant fibroblasts, and 15 displayed an EC50 as low as 1 nM for several human cancer cell lines.