[:pb]Synthesis, potent anti-TB activity against M. tuberculosis ATTC 27294, crystal structures and complex formation of selected 2-arylidenehydrazinylbenzothiazole derivatives[:]

[:pb]Authors: Pinheiro, A. C.; De Souza, M. V. N.; Lourenço, M. C. S.; Da Costa, C. F.; Baddeley, T. C.; Low, J. N.; Wardell, S. M. S. V. ; Wardell, J. L.
Source: Journal of Molecular Structure, v. 1178, p. 655-668, 2019
Publisher: Science Direct

Abstract

The synthesis, anti-TB activity, crystal structures and ligand ability of a number of 2-arylidene-benzylidenehydrazinylbenzothiazole derivatives, 1, have been investigated. The compounds 1 were obtained from 2-hydrazinobenzothiazole and substituted benzaldehydes in refluxing methanol in yields, after recrystallisation, of 55–75%. The crystal structure determination of compounds, 1e (aryl = 4-MeOC₆H₄), 1h (aryl = pyridin-2-yl), 1f (aryl = 2-HO-5-MeC₆H₃) revealed amino forms, whereas an imino form was found for 1f (aryl = 2-HO-4-MeOC₆H₃). Despite the different tautomeric forms of 1e and 1h, the two compounds have similar cell dimensions and furthermore their intermolecular interactions combine to form similar sub-structures. Pairs of NH⋯N hydrogen bonds and π···dπ stacking interactions produce dimers in all compound. The compounds with the best anti-mycobacterial activity were found to be 1c (aryl = 2-O₂NC₆H₄), 1d, (aryl = 2-HOC₆H₄), 1e and 1h, all having superior activities to that of the standard drug, ethambutol. Moreover two of these compounds have the capacity to act as tridentate ligands, namely 1d [a potential ONN chelator] and 1h [a potential NNN chelator]. Compound 1d (HL) acts as a tridentate O,N,N-donor to Cu^(II) in forming the dimeric octahedral complex{[(L) (H₂O)Cu][ O₃SCF₃]}₂, 3, from Cu^{(II) (}O₃SCF₃)₂ in moist MeOH. The monomeric square-pyramidal [(L) (H₂O)Cu][ O₃SCF₃], with an axial OS(O₂)CF₃ ligand and equatorial H₂O ligand, dimerizes through extensive π···π interactions involving two complete planar L-Cu fragments. The dimers are linked into a three dimensional array by OH⋯O and NH⋯O hydrogen bonds and by further π···π interactions. Complex 3, while still very active, has only about 40% of the activity of its ligand against M. tuberculosis ATTC 27294.

Keywords: 2-Arylidenehydrazinylbenzothiazole derivatives: crystal structure determinations, anti-TB activity,

Document Type: Research Article

DOI: 10.1016/j.molstruc.2018.10.030

Publication date: 15 de fevereiro de 2019[:]