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

Biomed Pharmacother. 2018 Jul:103:1337-1347. doi: 10.1016/j.biopha.2018.04.163. Epub 2018 May 7.

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.

Keywords: 1,3-Thiazolidin-4-one; Analgesic activity; Antimicrobial activity; Antiproliferative activity; Hydrazide-hydrazone.

MeSH terms

  • Analgesics / pharmacology
  • Animals
  • Anti-Infective Agents / pharmacology
  • Behavior, Animal
  • Cell Death / drug effects
  • Cell Line
  • Humans
  • Hydrazones / chemical synthesis*
  • Hydrazones / chemistry
  • Hydrazones / pharmacology*
  • Inhibitory Concentration 50
  • Mice
  • Microbial Sensitivity Tests
  • Thiazolidines / chemical synthesis*
  • Thiazolidines / chemistry
  • Thiazolidines / pharmacology*

Substances

  • Analgesics
  • Anti-Infective Agents
  • Hydrazones
  • Thiazolidines