Rhodacyanine dyes and several analogous delocalized lipophilic
cations (DLCs) were synthesized and evaluated as novel
antitumor agents.
Rhodacyanine dye consists of two heteroaromatic rings such as
thiazoles at both termini of the conjugate systems and
4-oxothiazolidine (
rhodanine) in the middle of it. Compounds with such a unique double-conjugate structure were found to inhibit the growth of several tumor cell lines, such as colon
carcinoma CX-1, and to exhibit relatively low toxicity against normal kidney cell line
CV-1 (e.g., IC50(CX-1) = 50 nM, IC50(CV-1) = 17.3 microM; selectivity index = 346 for compound 5). These compounds were also found to be efficacious in the
tumor-bearing nude mice model (e.g., against human
melanoma LOX; T/C (%) = 168 for compound 5). Structural modifications on
rhodacyanine, including deletion of a heteroaromatic ring involved in the
merocyanine conjugate system and replacement of
rhodanine with a structurally related moiety such as 4-oxoimidazolidine or 4-oxo-1,3-dithiolane, resulted in a loss of the selectivity and/or the activity. Our current structure-activity studies imply that the double-conjugate system with a
rhodanine moiety is essential for the selective activity of
rhodacyanine dyes, and we find this class of compounds as unique
antitumor agents candidates.