Hemijska Industrija (Jan 2009)

Synthesis and cytotoxic activity of a series of bile acid derivatives

  • Kuhajda Ksenija N.,
  • Cvjetićanin Stanko M.,
  • Đurendić Evgenija A.,
  • Sakač Marija N.,
  • Penov-Gaši Katarina M.,
  • Kojić Vesna V.,
  • Bogdanović Gordana M.

DOI
https://doi.org/10.2298/HEMIND0904313K
Journal volume & issue
Vol. 63, no. 4
pp. 313 – 318

Abstract

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The new conjugates of selected bile acids (hyocholic (2), deoxycholic (3), hyodeoxycholic (4) and 12-ketocholic (5) acids) with ethyl 11-aminoundecanoate 7, 8, 11, and 13 were synthesized. The conjugation reaction was carried out in ethyl acetate in the presence of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) and triethylamine. Under the same experimental conditions, the conjugation reaction involving ethyl 6-aminohexanoate resulted in formation of a conjugate 9 only in the case of deoxycholic acid (3) in addition to the unexpected ethyl ester 10. In the case of the other bile acids (cholic (1), hyodeoxycholic (4) and 12-ketocholic (5) acids) only an unexpected ester formation took place giving esters 6, 12, and 14. Cytotoxic activity against four tumor cell lines (human breast adenocarcinoma ER-, MDA-MB-231; breast adenocarcinoma ER+, MCF-7; cervix epiteloid carcinoma, HeLa S-3; and prostate cancer, PC-3) was evaluated. Conjugate 8 showed strong activity against HeLa S-3 and conjugate 11 for PC-3. Ethyl ester of 12-ketocholic acid 14 showed very strong antiproliferative activity against MCF-7 and HeLa S-3.

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