Abstract:
A chemical library of N, N'-Disubstituted thioureas have been derived from substituted aromatic
carboxylic acids and two types of combinatorial strategies have been employed for the
construction of chemical library. For high throughput screening of components of the chemical
library, solution-phase pool syntheses have been exercised, where each pool consists of four
components. All the members of chemical library have also been synthesized by using a parallel
mode of solution-phase combinatorial synthesis for the purpose of lead screening/identification,
testing, characterization and for assembling of Cu(I), Cu(II) & Pd(II) metal complexes. Copper(I)
(1A-19A, 1B-19B, 1C-19C& 1F) and palladium(II) [(1E-14E)] complexes of N, N'-disubstituted
thioureas have only been synthesized with some selected thioureas from sub-library-1 and Cu(II)
complexes (1D-6D) with isoureas (1-6), prepared from the thioureas derived from benzoic acid.
All the thioureas (1a-40a, 1b-40b, 1c-40c, 1d-40d, 1e-40e, 1f-40f & 1g-40g) and complexes
have been characterized by elemental analyses, FT-IR, 1 H &
13
C NMR spectroscopy, mass
spectrometry and single crystal XRD. The stability of the Cu(I) complexes in the test medium has
been confirmed by cyclic voltammetric studies. The products of pool syntheses (pools 1-40) have
been characterized by mass spectrometry and GC-MS (gas chromatograph coupled with mass
spectrometer) techniques. In all the Cu(I) and Pd(II) complexes, neutral N, N′-disubstituted
thiourea ligands have been coordinated to the metal atom through the sulphur atom in a terminal
mode except (1F), where the deprotonation of NH group of the thiourea ligand has facilitated the
bonding of copper atom through N and S. The isoureas (1-6) show bidentate behavior in Cu(II)
complexes having square planar geometry (1D-6D).
The thioureas have also been examined for their fungicidal properties and these show
significant activity against various fungi strains and low phytotoxicity for the representative
monocot plant species. The complexes have been screened for their in vitro cytotoxicity in human
cell lines carcinomas A498 (renal), EVSA-T (breast), H226 (lung), IGROV (ovarian), M19
(melanoma-skin), MCF-7 (breast) and WIDR (colon). They show a moderate cytotoxicity against
these seven human cancer cell lines in comparison to that of the less active standard
chemotherapeutic drugs. Biological screening of the synthesized thioureas and their metal
complexes for various targets is in progress.