Hydrazones and N-acylhydrazones

Due to its synthetic and biological versatility, hydrazone and N-acylhydrazone groups are attractive functional groups for the development of new drugs. Numerous biological activities associated with hydrazones have been reported in the literature, such as antidepressive, anticonvulsive, antiinflammatory, antimicrobial and antimycobacterial.

 

Our research group synthesized and evaluated various hydrazones and N-acylhydrazones containing different heteroaromatic nuclei such as isoniazid and pyrazinamide derivatives (two drugs of first choice in the treatment of tuberculosis), pyridines, pyrimidines, quinolines, quinoxalines, coumarins, thiophenic, furanic and thiadiazolic nuclei.

In addition to these nuclei, amino acid derivatives were also synthesized and evaluated. These derivatives showed promising anticancer activities and it is worth noting that these classes were also tested for tuberculosis, malaria and leishimania. Activities varied depending on the nucleus, position and the substituents employed on the aromatic and heteroaromatic rings.

 

 

Tests commonly used in the pharmacological evaluation of synthesized substances

In vitro cytotoxicity in cells

MTT Method

MTT cytotoxicity analysis has been used in the US National Cancer Institute (NCI) screening program, with the ability to analyze the viability and metabolic state of the cell and is a fast, sensitive and inexpensive method .

The methodology employed is based on the conversion of yellow-colored 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyl) tetrazolium bromide (MTT) salt after solubilization in water into formazan crystals of Color blue purple. The conversion of MTT occurs only in viable and metabolically active cells, in a blue / black crystal of formazan, through the action of mitochondrial dehydrogenase enzymes, which allows the indirect quantification of the percentage of live cells. The insoluble product formed can be dissolved by some solvents and its quantification is performed from absorbance using a spectrophotometer. Thus, the cytotoxic study by the MTT method allows easy definition of cytotoxicity, but not the mechanism of action of the substances tested.

The most tested tumor lines with our synthetic products are OVCAR-8 (human ovary), HL-60 (human promyelocytic leukemia), HCT-116 (human colon), SF-295 (human glioblastoma), K-562 (myeloid leukemia Chronic), PC-3 (Prostate Adenocarcinoma), MCF7 (Breast Adenocarcinoma) and HEPG2 (hepatocellular carcinoma).