Synthesis and biological evaluation of N-aryl-2-phenyl-hydrazinecarbothioamides: Experimental and theoretical analysis on tyrosinase inhibition and interaction with HSA

Synthetic (E)-3-Phenyl-5-(phenylamino)-2-styryl-1,3,4-thiadiazol-3-ium Chloride Derivatives as Promising Chemotherapy Agents on Cell Lines Infected with HTLV-1

“…The intermediates 4a-d were prepared in solvent free conditions using a grinding method with aryl-isothiocyanates and phenyl-hydrazine at room temperature for 2 min. These compounds were obtained in quantitative yields and high purity, and their structures were confirmed by FT-IR spectroscopy and NMR 1 H and 13 C spectrometry, in accordance with previous publications on mesoionic compounds [29,50]. The (E)-3-phenyl-5-(phenylamino)-2-styryl-1,3,4-thiadiazol-3-ium chloride derivatives (5a-d) were prepared by reaction of cinnamaldehyde and the N-aryl-2-phenyl-hydrazinecarbothioamides (4a-d) in equimolar amounts, thionyl chloride (excess of three times), and enough drops of 1,4dioxane to homogenize the reagents.…”

“…The intermediates 4a-d were prepared in solvent free conditions using a grinding method with aryl-isothiocyanates and phenyl-hydrazine at room temperature for 2 min. These compounds were obtained in quantitative yields and high purity, and their structures were confirmed by FT-IR spectroscopy and NMR 1 H and 13 C spectrometry, in accordance with previous publications on mesoionic compounds [29,50]. with HTLV-1 and a Jurkat cell line (lymphocytic leukemia).…”

“…These values are about four orders of magnitude higher than for the water limiting diffusion rate constant (kdiff ~ 7.40 × 10 9 M −1 s −1 , at 298K [63]). This is an indication that the fluorescence quenching mechanism must be static, involving an association in the ground-state between albumin and mesoionic compounds 5a-d [50]. In addition, the values for the Stern-Volmer constant (KSV) at different temperatures are similar ( Table 2), suggesting that 5a-d show similar binding capacity towards HSA.…”

“…The steady-state fluorescence spectra for HSA (1.00 × 10 −5 M) in the absence and presence of successive additions of mesoionic compounds 5a-d (concentration up to 1.32 × 10 −5 M) are shown in Figure S6 in the Supplementary Material. In the presence of these compounds, it is possible to observe the quenching of the fluorescence emission of the protein (λ em = 340 nm), which indicates the existence of a possible interaction between the Trp-214 residue, responsible for the emission of albumin, and 5a-d [50,61]. The addition of any of these mesoionic compounds to the HSA solution did not result in a shift in the maximum fluorescence emission, indicating that the HSA:mesoionic compound interaction does not disturb the microenvironment surrounding the Trp-214 residue [46].…”

“…These two peaks correspond to the π-π * and n-π * transitions, respectively [70]. After adding a solution of the mesoionic compounds 5a-d (1.32 × 10 −5 M) to the HSA solution (1.00 × 10 −5 M), a small decrease in intensity at 208 nm and 222 nm was clearly observed ( Figure S11, Supplementary Material), indicating a slight change in the secondary structure of the HSA [50]. The variation in the secondary structure of albumin is about 5.0% in all cases, which is evidence that the 5a-d interaction can occur with a very slight disturbance in the secondary structure of albumin (Table 4) [71].…”