Synthesis and in vitro bioactivity study of new hydrazide-hydrazones of 5-bromo-2-iodobenzoic acid

Abstract

In this study 14 novel hydrazide-hydrazones of 5-bromo-2-iodobenzoic acid (3-16) were synthesized on the basis of condensation reaction. The chemical structure of obtained derivatives was established on the basis of spectral data (¹H NMR and ¹³C NMR) and the lipophilicity of synthesized molecules was determined with the use of RP-HPTLC chromatography. Synthesized hydrazide-hydrazones (3-16) were subjected to in vitro cytotoxicity assay and antimicrobial activity analysis against a panel of bacteria and fungi. Among newly synthesized derivatives (3-16), compound 5 was characterized by high, selective and the most diverse cytotoxicity to the cancer cell lines. Molecules 7 and 9 which were substituted with a nitro group in the phenyl ring also exhibited very significant inhibitory effect in the tumor cells and they were very selective. Similarly, compound 13 showed high antiproliferative activity against both cancer cell lines (769-P, HepG2) with satisfactory selectivity. In turn, molecule 8 was characterized by lower inhibitory effect in tumor cells but high selectivity. Derivative 16 proved to be toxic mainly to 769-P cells plausibly by the inhibition of COX-2 mediated signalling pathway. In summary, the introduction of chloro substituent or nitro group to the molecule proved to be most advantageous, providing high cytotoxicity and selectivity to tumor cells. However, the presence of indole scaffold appeared to be responsible for COX-2 inhibitory effect. Some of synthesized hydrazide-hydrazones possessed also moderate antimicrobial activity against a panel of microorganisms.

Keywords: 769-P cell line; Antimicrobial activity; Antiproliferative activity; COX-2; HepG2 cell line; Hydrazide-hydrazone; MBC; MIC; MTT assay; Vero cell line.