Synthesis, characterisation, X-ray diffraction and biological evaluation of new thiourea derivatives against Mycobacterium tuberculosis and cervical cancer

Abstract

In this study, thiourea derivatives were prepared to identify potentially effective compounds against tuberculosis and cervical cancer. The newly synthesized compounds, namely N-(cyclohexyl(methyl)carbomothioyl) benzamide (TU1), N-(cyclohexyl(methyl)carbamothioyl)-2-methylbenzamide (TU2), N-(dicyclohexylcarbamothioyl) benzamide (TU3), N-(dicyclohexylcarbamothioyl)-4-nitrobenzamide (TU4), N-(diphenylcarbamothioyl) benzamide (TU5), and N-(diphenylcarbamothioyl)-4-nitrobenzamide (TU6), were obtained in high purity and yields. The compounds were successfully characterized by infrared spectroscopy (IR), ultraviolet-visible spectroscopy (UV-Vis), nuclear magnetic resonance (NMR), single crystal X-ray diffractometer (SCXRD), mass spectrometry (MS) and the melting points (mp). Crystal structure analyses of TU1, TU2 and TU6 were carried out which showed, that in the solid state, the molecules were linked together by intermolecular hydrogen bonds, specifically NH⋯S and CH⋯O interactions. In-vitro testing against M. tuberculosis (Mtb) revealed compounds TU1 and TU2 to be the most potent with MIC90 values of 28.2 and 11.2 μM, respectively. However, compounds TU4, TU5, and TU6, with MIC90 values of 80.3, 82.8 and 107.7 µM, respectively, exhibit mild antituberculosis activity, whereas TU3 with a MIC90 value of 752.7 µM is considered inactive against the Mtb strain. None of the compounds demonstrated significant selectivity for bacterial cells versus human cells and thus further studies could be dedicated to creating derivatives of TU1 and TU2 that are more selective. In vitro biological screening against HeLa cells revealed two highly toxic compounds, TU2 and TU6, with respective IC50 values of 12.00 ± 1.21 μM (SI = 1.06) and 8.45 ± 1.21 μM (SI = 0.08); and two moderately toxic compounds, TU4 (IC50 = 27.75 ± 1.15 µM; SI = 0.35) and TU5 (IC50 = 23.66 ± 1.24 µM; SI = 0.29).