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

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.