Synthesis and Characterization of Novel n-9 Fatty Acid Conjugates Possessing Antineoplastic Properties

• Published in: Lipids 2012-10, Vol.47 (10), p.973-986
• Main Authors: Khan, Azmat A., Husain, Ahmad, Jabeen, Mumtaz, Mustafa, Jamal, Owais, Mohammad
• Format: Article
• Language: English
• Subjects: Antineoplastic; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Biomedical and Life Sciences; Cancer cell line; Caspase‐3; Cell Adhesion; Cell Line, Tumor; Cell Movement; Cell Survival; Cytochrome c; Cytotoxicity; Dose-Response Relationship, Drug; Ester conjugates; Esters; Fatty acids; Fatty Acids, Unsaturated - chemical synthesis; Fatty Acids, Unsaturated - chemistry; Humans; Life Sciences; Lipidology; Medical Biochemistry; Medicinal Chemistry; Melanoma; Microbial Genetics and Genomics; Neurochemistry; Nutrition; Oleic Acid - chemical synthesis; Oleic Acid - chemistry; Original Article; Propofol - chemistry; Propofol - pharmacology; Ricinoleic Acids - chemical synthesis; Ricinoleic Acids - chemistry
• ISSN: 0024-4201; 1558-9307
• DOI: 10.1007/s11745-012-3707-9

The present study enumerates the synthesis, spectroscopic characterization, and evaluation of anticancer potential of esters of two n-9 fatty acids viz., oleic acid (OLA) and ricinoleic acid (RCA) with 2,4- or 2,6-diisopropylphenol. The synthesis strategy involved esterification of the hydroxyl group of diisopropylphenol (propofol) to the terminal carboxyl group of n-9 fatty acid. The synthesized propofol-n-9 conjugates having greater lipophilic character were tested initially for cytotoxicity in-vitro. The conjugates showed specific growth inhibition of cancer cell lines whereas no effect was observed in normal cells. In general, pronounced growth inhibition was found against the human skin malignant melanoma cell line (SK-MEL-1). The anticancer potential was also determined by testing the effect of these conjugates on cell migration, cell adhesion and induction of apoptosis in SK-MEL-1 cancer cells. Propofol-OLA conjugates significantly induced apoptosis in contrast to propofol-RCA conjugates which showed only weak signals for cytochrome c . Conclusively, the synthesized novel ester conjugates showed considerable moderation of anti-tumor activity. This preliminary study places in-house synthesized conjugates into the new class of anticancer agents that possess selectivity toward cancer cells over normal cells.