β-11-Keto-boswellic acid derived amides: synthesis and cytotoxicity

Abstract

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