Anticancer Activity of 3-O-Acylated Betulinic Acid Derivatives Obtained by Enzymatic Synthesis

• Published in: Bioscience, biotechnology, and biochemistry Vol. 74; no. 5; pp. 1025 - 1029
• Main Authors: AHMAD, Faujan Bin H., GHAFFARI MOGHADDAM, Mansour, BASRI, Mahiran, ABDUL RAHMAN, Mohd Basyaruddin
• Format: Journal Article
• Language: English
• Published: Tokyo Japan Society for Bioscience, Biotechnology, and Agrochemistry 2010; Japan Society for Bioscience Biotechnology and Agrochemistry; Oxford University Press
• Subjects: 3-O-acyl-betulinic acid; Acylation; anticancer agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; betulinic acid; Biocatalysis; Bioconversions. Hemisynthesis; Biological and medical sciences; Biotechnology; Candida - enzymology; Candida antarctica; Cell Line, Tumor; enzymatic synthesis; Fundamental and applied biological sciences. Psychology; Humans; Inhibitory Concentration 50; Lipase - metabolism; Methods. Procedures. Technologies; Novozym 435; Solvents - chemistry; Triterpenes - chemical synthesis; Triterpenes - chemistry; Triterpenes - metabolism; Triterpenes - pharmacology; Antineoplastic agent; Enzymatic synthesis; 3-O-acyl-betulinic acid; Novozym 435; betulinic acid; anticancer agents
• ISSN: 0916-8451; 1347-6947
• DOI: 10.1271/bbb.90917

An easy and efficient strategy to prepare betulinic acid esters with various anhydrides was used by the enzymatic synthesis method. It involves lipase-catalyzed acylation of betulinic acid with anhydrides as acylating agents in organic solvent. Lipase from Candida antarctica immobilized on an acrylic resin (Novozym 435) was employed as a biocatalyst. Several 3-O-acyl-betulinic acid derivatives were successfully obtained by this procedure. The anticancer activity of betulinic acid and its 3-O-acylated derivatives were then evaluated in vitro against human lung carcinoma (A549) and human ovarian (CAOV3) cancer cell lines. 3-O-glutaryl-betulinic acid, 3-O-acetyl-betulinic acid, and 3-O-succinyl-betulinic acid showed IC 50 <10 μg/ml against A549 cancer cell line tested and showed better cytotoxicity than betulinic acid. In an ovarian cancer cell line, all betulinic acid derivatives prepared showed weaker cytotoxicity than betulinic acid.