Synthesis, characterization and in vitro anti-Trypanosoma cruzi and anti-Mycobacterium tuberculosis evaluations of cyrhetrenyl and ferrocenyl thiosemicarbazones

•Ferrocenyl and unreported cyrhetrenyl thiosemicarbazones have been prepared.•Crystal structure of cyrhetrenyl thiosemicarbazone.•Ferrocenyl derivatives are better trypanocidal than their cyrhetrenyl analogues.•Cyrhetrenyl and ferrocenyl thiosemicarbazones are moderated antitubercular agents.

To study the electronic influence of the organometallic moieties in thiosemicarbazones, two short libraries of cyrhetrenyl thiosemicarbazone and ferrocenyl thiosemicarbazone hybrids were synthesized and tested for their antichagasic and antitubercular activities. The unreported cyrhetrenyl thiosemicarbazone derivatives of the form [(η5-C5H4)–C(R1) = NNHC(S)NHR2]Re(CO)3 (R1 = H, CH3; R2 = H, CH3, CH2CH3, C6H5) were prepared from cyrhetrenylcarbaldehyde (1a) or acetylcyrhetrene (1b) and the corresponding thiosemicarbazide. The 1H and 13C NMR spectra indicate that these compounds have the anti-(E) conformation in solution, and the X-ray crystal structure of formylcyrhetrene 4-methyl-thiosemicarbazone (2b) confirms that this complex also adopts the anti-(E) form in the solid state. The new cyrhetrenyl thiosemicarbazones and their ferrocene analogues were screened in vitro against Trypanosoma cruzi and Mycobacterium tuberculosis. The anti-T. cruzi evaluation showed that the ferrocenyl derivatives were more efficient trypanocidal agents compared to their cyrhetrenyl counterparts. The incorporation of any organometallic fragment into thiosemicarbazone scaffold showed moderate antituberculosis activity against mc27000 strain.

Graphical abstractCyrhetrenyl thiosemicarbazones were synthesized and characterized by spectroscopy and X-ray crystallography and their properties compared to their ferrocenyl analogues. Compounds were evaluated against Trypanosoma cruzi and Mycobacterium tuberculosis strains. Ferrocenyl thiosemicarbazones were more efficient trypanocidal agents compared to their cyrhetrenyl counterparts. Both series of organometallic thiosemicarbazones showed moderate antitubercular activity.Figure optionsDownload full-size imageDownload as PowerPoint slide