Synthesis, characterization and biological evaluation of bile acid-aromatic/heteroaromatic amides linked via amino acids as anti-cancer agents

• Series of bile acid aryl/heteroaryl amides linked via α-amino acid were synthesized.
• Cytotoxic behavior against HT29, MDAMB231, U87MG were tested.
• Three conjugates showed good in vitro activity (GI50 = 1.35, 1.41, 4.52 μM) against MDAMB231.
• Another three conjugates showed good in vitro activity (GI50 = 2.49, 2.46, 1.62 μM) against U87MG.
• Greater than 65% of the synthesized compounds were found to be safer on human normal cell line (HEK293T).

A series of bile acid (Cholic acid and Deoxycholic acid) aryl/heteroaryl amides linked via α-amino acid were synthesized and tested against 3 human cancer cell-lines (HT29, MDAMB231, U87MG) and 1 human normal cell line (HEK293T). Some of the conjugates showed promising results to be new anticancer agents with good in vitro results. More specifically, Cholic acid derivatives 6a (1.35 μM), 6c (1.41 μM) and 6m (4.52 μM) possessing phenyl, benzothiazole and 4-methylphenyl groups showed fairly good activity against the breast cancer cell line with respect to Cisplatin (7.21 μM) and comparable with respect to Doxorubicin (1 μM), while 6e (2.49 μM), 6i (2.46 μM) and 6m (1.62 μM) showed better activity against glioblastoma cancer cell line with respect to both Cisplatin (2.60 μM) and Doxorubicin (3.78 μM) drugs used as standards. Greater than 65% of the compounds were found to be safer on human normal cell line.

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