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

Abstract

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.

Biophysical Interactions of Novel Oleic Acid Conjugate and its Anticancer Potential in HeLa Cells

“…The IC 50 value of 4.6 μM clearly marks the potent nature of 2,6P-OLA on HeLa cells. The cytotoxic effect of conjugate on HeLa cells is in agreement with its previously reported results on other cancer cell lines [1]. The structural modifications of propofol and oleic acid impart extra edge on the final product, thereby placing it in a class of anticancer agents depicting selectivity and specificity.…”

“…Briefly, 5×10 5 cells/ well in exponential growth were seeded into 96-well plates and were treated with increasing concentration of 2,6P-OLA from 0 to 15 μM [1]. After 94 h, MTT reagent (5 mg/ml PBS) was added to each well at the ratio of 1:10 (v/v).…”

“…2,6-Diisopropylphenol-Oleic acid (2,6P-OLA); is a novel oleic acid conjugate that possess potent antineoplastic properties. Because of its inhibitory and apoptotic action on cancer cells, in vitro [1], it has a potential of being characterised as a member of a new class of fatty acid based anticancer agents [2][3][4][5][6][7]. 2,6P-OLA as of now, has not been exploited for its interaction abilities with various biological targets.…”

Transdifferentiation of MALME-3M and MCF-7 Cells toward Adipocyte-like Cells is Dependent on Clathrin-mediated Endocytosis

“…Our results also indicate that certain albumin complex associated poly-and monounsaturated fatty acids induce terminal differentiation and arrest cancer progression (Ruiz-Vela et al 2011). Concomitanlty to our studies, Khan et al have also described the specific growth inhibition of esters of oleic acid and ricinoleic acid against the human skin malignant melanoma cell line (SK-MEL-1) (Khan et al 2012). Despite the important findings that we describe here, many key questions remain unanswered in the identification of novel genes and proteins that mediate the terminal transdifferentiation of human cancer cells.…”

Study on Synthesis, Characterization and Antiproliferative Activity of Novel Diisopropylphenyl Esters of Selected Fatty Acids

“…It is interesting to observe that there was a clear difference in activity among isomers of 2,4-and 2,6-diisopropylphenyl esters derived from same fatty acid on the cell lines tested except on Mia-Pa-Ca where the difference in activity was less between two isomers. Earlier reports on the propofol-fatty acid conjugates also showed similar observations on cancer cell lines where the fatty acids used were normal long chain fatty acids 6,19 .…”