The coupling of acetylated piperazinylamide spacered triterpenoic oleanolic acid and ursolic acid with meta or para substituted carboxylated malachite green analogs gave conjugates 10, 11, 15, and 16 that were cytotoxic for several human tumor cell lines. Especially, an oleanolic acid-derived compound 10 was cytotoxic for MCF-7 human breast carcinoma cells (EC 50 = 0.7 μM). These derivatives represent first examples of triterpenoic acid derivatives holding a cationic scaffold derived from malachite green.
Graphical Abstract
Oxidation of 2,3-dehydro-11-keto--boswellic acid gave derivatives holding extra hydroxyl groups at positions C-1, C-2 or C-1 and C-9, respectively. The synthesis of 2,3-dehydro-1,9-dihydroxy-11-keto--boswellic acid represents the first partial-synthetic access to this class of compounds. The synthetic strategy can be expanded easily, and a corresponding analogue derived from glycyrrhetinic acid was accessed by the same synthetic scheme in good overall yield. Boswellic and glycyrrhetinic acid 1,9-endoperoxides are intermediates for the synthesis of the 1,9-dihydroxylated compounds. These 1,9-endo-peroxides were highly cytotoxic for several human tumor cell lines but only diminished cytotoxicity was observed in SRB assays for the 1,9-dihydroxylated compounds.
The aim of this study was to prepare 11-keto-β-boswellic acid derivatives modified at C-24 and to evaluate their in vitro cytotoxicity. Acetyl-11-keto-β-boswellic acid (AKBA) was isolated from frankincense and transformed into 11-keto-β-boswellic acid (KBA). Both compounds served as starting materials for the synthesis of several amides or hydrazides. The derivatives were fully characterized, and their cytotoxicity was evaluated in vitro using sulforhodamine B (SRB) assays employing two human tumor cell lines (A2780 and MCF7) as well as nonmalignant mouse fibroblasts (NIH 3T3). Nearly all of the compounds were more cytotoxic than their parent compounds. The highest cytotoxicity was observed for (3 α, 4 β) 3-acetyloxy-N-(3- aminopropyl)-11-oxo-urs-12-en-24-amide (15) and (3 α, 4 β) 3-acetyloxy-N-[4-(3-aminopropyl)piperazin-1-yl]- propyl-11-oxo-urs-12-en-24-amide (16) and the ovarian carcinoma cell line A2780. These compounds showed EC50 = 1.0-1.7 µM while being significantly less toxic for the mouse fibroblasts NIH 3T3 (EC50 = 9.3-16.3µM). Thus, compounds 15 and 16 have good antitumor effects and may serve as starting points for developing potential and selective antitumor agents
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