New hydrazide-hydrazones and 1,3-thiazolidin-4-ones with 3-hydroxy-2-naphthoic moiety: Synthesis, in vitro and in vivo studies

Abstract In this research we synthesized, identified and evaluated new hydrazide-hydrazones (1–3) and 1,3-thiazolidin-4-one derivatives (4–6) for in vitro and in vivo activity. New hydrazide-hydrazones (1–3) were obtained by the condensation reaction of 3-hydroxy-2-naphthoic acid hydrazide with appropriate aldehydes. Synthesized hydrazide-hydrazones (1–3) were subjected to cyclization reaction with mercaptoacetic acid which afforded with new 1,3-thiazolidin-4-one derivatives (4–6). Among 1,3-thiazolidin-4-one derivatives tested (4–6), compound 6 exhibited highest and most selective cytotoxicity towards human renal adenocarcinoma cells (769-P) and it did not affect the growth of normal cells (H9c2, GMK). Whereas its hydrazide-hydrazone (compound 3) showed significant antiproliferative activity against both tested human cancer cell lines: renal adenocarcinoma (769-P) and hepatocellular carcinoma (HepG2), however with less selectivity. The in vivo studies focused on the antinociceptive activity of newly synthesized 1,3-thiazolidin-4-one derivatives (4–6). The preliminary screening of novel compounds showed that 1,3-thiazolidin-4-one derivatives (4–6) are safe and not toxic against CNS of mice. Among tested derivatives one compound (6) displayed significant analgesic activity.