Nitroisatin dithiocarbazate: Synthesis, structural characterization, DFT, and docking studies

Abstract

The reaction between 5-nitroisatin with S-benzyl dithiocarbazate affords a new isatindithio carbazate so-called NO₂Isadtc (Benzyl 2-(5-nitro-2-oxoindolin-3-ylidene)hydrazinecarbodi thioate) which was characterized by means of ¹H NMR, FT-IR, UV-visible and single crystal X-ray diffraction - Crystal data for C₁₆H₁₂N₄O₃S₂ (M =372.42 g/mol): triclinic space group P-1, (n°. 02), a = 6.640 Å, b = 8.256 Å, c = 15.908 Å, V = 849.6 ų, Z = 2, T = 293 K, μ(MoK_α) = 0.337 mm^-1, D_calc = 1.456 g/cm³, 27515 reflections measured (2.499° ≤ 2Θ ≤ 26.524°), 3518 unique (R_int = 0.0533, R_sigma =0.0222) which were used in all calculations. The final R₁ was 0.0367 (I > 2σ(I)) and wR₂ was 0.1045 (all data). Computational methods were applied to NO₂Isadtc and its nonsubstituted parent compound Isadtc for structure optimization, electronic distribution, and infrared calculations using B3LYP functional with 6-31G(d,p) basis set in ethanol as a polarizable continuum model. Furthermore, docking studies using human thioredoxin reductase 1 (TrxR) as enzyme target also were performed using NO₂Isadtc and the optimized structure of Isadtc. The results demonstrated that both NO₂Isadtc and Isadtc may act as inhibitors of TrxR, having different interactions detected, highlighting the contact between the NO₂ group and the S111 at the helix which is found for NO₂Isadtc.