Hydrazones derived from natural aldehydes: in vitro cytotoxic evaluation and in silico pharmacokinetic predictions

Abstract

Introduction: Recent research has reported the cytotoxic potential of hydrazones against various strains of cancer cells. Aim: To evaluate the anticancer activity in vitro and the pharmacokinetic profile of six synthesized hydrazonic compounds, identified as vanillin 1-phthalazinylhydrazone (VAN-1); 2,4-dinitrophenylhydrazone vanillin (VAN-2); phenylhydrazone cinnamaldehyde (CIN-1); isonicotinoyl hydrazone cinnamaldehyde (CIN-2); cinnamaldehyde 1 phthalazinylhydrazone (CIN-3); and 2,4 dinitrophenylhydrazone cinnamaldehyde (CIN-4). Thecytotoxic activity was evaluated against four strains of cancer cells. Methodology: Thepharmacokinetic parameters of absorption, distribution, metabolism, excretion, and toxicity (ADME/T) of the hydrazones were evaluated using the PreADMET program. Results: Hydrazones derived from cinnamaldehyde (CIN-1 and CIN-2) showed high cytotoxic activity against leukemic (HL-60) and glioblastomas (SF-295) cell lines. The pharmacokinetic profile of the hydrazones showed that, in general, the hydrazones presented satisfactory characteristics of ADME/T. In addition, it was observed that CIN-2 presented the most promising in silico profile, showing high intestinal absorption, desirable distribution profile related to plasma protein binding, adequate renal excretion, and low toxicity. The ADME/T profile of the CIN-1 compound highlighted its potential as a promising antineoplastic agent with action of the CNS, more specifically against glioblastomas.

Hydrazone Molecular Switches with Paramagnetic Center as 19F Magnetic Resonance Imaging Relaxation Enhancement Agents for pH Imaging

“…Additionally, Gd­(III) complexes with similar structures are widely used in medical diagnostics and are considered safe at small doses . The aromatic hydrazones with a similar structure were found to be weakly mutagenic but not carcinogenic, exhibiting good renal excretion and low toxicity toward healthy tissues and cells . This suggests the potential usefulness of the proposed probes in vivo , which we will study further.…”