Synthesis of New Thiosemicarbazone Derivatives Substituted with Heterocycles with Potential Antitumor Activity

Aims: To find new thiosemicarbazone derivatives with antitumor activity and good physico-chemical parameters.

Study Design: A preliminary SAR study with pyrrolidinyl, piperidinyl, and morpholinyl heterocycles as well as hydrogen, alkyl and phenyl groups in the thiosemicarbazone scaffold.

Place and Duration of Study: Department of Pharmaceutical Sciences and Department of Antibiotics, from Federal University of Pernambuco (Brazil), between January 2016 and February 2017.

Methodology: The thiosemicarbazones were synthesized through a condensation reaction between benzaldehyde substituted with heterocycles and several thiosemicarbazides, using a catalytic amount of hydrochloric acid. The new compounds were characterised using classical spectroscopic and spectrometric techniques. The cytotoxicity were evaluated using MTT assay against five cancer cell lines and doxorubicin as reference compound. The LogP was also predicted using the software MarvinSketch 17.4.3 and promising results were found.

Results: We found five new thiosemicarbazone derivatives with excellent cytotoxicity.

Conclusion: Thiosemicarbazone derivatives are promising compounds in medicinal chemistry field and certainly should be considered as scaffold for drug candidates.