## 2 Materials and Methods  
### Chemistry  
All reactions were monitored by analytical thin layer chromatography using Merck pre-coated silica gel plates with F254 indicator. Melting points were determined using a Thermoscientific 9200 capillary melting point apparatus (Philadelphia, PA, USA). 1H and 13C NMR spectra were recorded on a Varian Mercury 400 Digital FT-NMR (400 MHz) instrument with tetramethylsilate as an internal standard in DMSO-d6 solutions. Chemical shifts (8) are reported in parts per million (ppm) and coupling constants (J) in Hertz with multiplicities, described as s = singlet, d = doublet, t = triplet, q = quartet, and m = multiplet. Mass spectrometry was conducted using a Micromass ZQ LC-MS spectrometer (ESI-mode) connected with Waters Alliance HPLC. The purities of the compounds were evaluated by Prominence series of a high-pressure liquid chromatography (HPLC) system with photodiode array detector (DAD). The chromatographic conditions were as follows: column, Raptor ARC-18 (100 \(\times\) 4.6 mm, 2.7 \(\upmu\)m); mobile phase, 0.1% formic acid/methanol mixture (35:65, _v/v_); flow rate, 0.8 mL/min; oven temperature, 25 \({}^{\circ}\)C, injection volume, 10 \(\upmu\)L. Column eluate was monitored at 254 nm. Working solutions of target compounds were prepared at different concentrations. Compound **3a** was registered in ScienceFinder with CAS number 889795-07-7 and was synthesized here with this method. The chemical structures of the compounds were established by using 1H- and 13C-NMR, and mass analysis spectroscopic methods, and their purities were determined with HPLC (Supplementary Materials Tables S1-S76). NOE spectra were recorded to identify the isomers obtained, and the compounds were E isomers (Figure 1). Synthesis of N\({}^{\prime}\)-(4-3/-2/-non-substituted benzylidene)-4-(hydroxy)benzoylhydrazzides_**(2a-t)**. _p_-Hydroxybenzoic acid hydrazide (compound 1) (3 mmol) was dissolved in ethanol (15 mL) and heated in a water bath under reflux with 4-/3-/2-/-non-substituted benzaldehyde (3 mmol) until the reaction was complete, as described previously [22]. It was stirred for approximately 20 h at room temperature, and the solid obtained was recrystallized from methanol. Synthesis of N\({}^{\prime}\)-(4-3/-2/-non-substituted benzylidene)-4-[(4-methylphenyl)sulfonyl) benzohydrazides_**(3a-t)**. _p_-Hydroxybenzoic acid 4-[(4-/3-/-2-/-non-substituted phenyl)methylene] hydrazide-hydrazzone (compound **2a-t**) (7 mmol) was mixed in dichloromethane solvent (10 mL) with K\({}_{2}\)CO\({}_{3}\) (10 mmol) and _p_-toluenesulfonyl chloride (7 mmol) in an ice bath, as described previously [23]. The progress of the final product formation was monitored by thin-layer chromatography (TLC; chloroform-methanol = 90:10). The solid obtained was purified by recrystallization from methanol-water. N\({}^{\prime}\)-(Phenylmethylidene)-4-[(4-methylphenyl)sulfonyl)benzoylhydrazzide_**(3a)**. Yield 65.0%. mp 199.8-200.5 \({}^{\circ}\)C. HPLC tR: 5.844 min, purity: 98.44%. 1H NMR (DMSO-d6, 400 MHz) \(\delta\): 2.40 (s, 3H, C1-CH3), 7.19-7.21 (d, 2H, J = 9.2 Hz, H\({}^{2}\)/, H\({}^{6}\)), 7.44-7.47 (t, 3H, J = 6.0 Hz, H3\({}^{\prime\prime}\), H4\({}^{\prime\prime}\), H5\({}^{\prime\prime}\)), 7.47-7.49 (d, 2H, J = 8.4 Hz, H2, H6), 7.72-7.74 (d, 2H, J = 8.0 Hz, H2\({}^{\prime\prime}\), H6\({}^{\prime\prime}\)), 7.76-7.79 (d, 2H, J = 8.4 Hz, H3, H5), 7.90-7.93 (d, 2H, J = 8.4 Hz, H3\({}^{\prime}\), H5\({}^{\prime}\)), 8.42 (s, 1H, N=CH), 11.90 (s, 1H, CONH). \({}^{13}\)C NMR (DMSO-d6, 100 MHz) \(\delta\): 21.18 (C1-CH3), 122.14 (C2\({}^{\prime}\), C6\({}^{\prime}\)), 127.14 (C2\({}^{\prime\prime}\), C6\({}^{\prime\prime}\)), 128.27 (C4\({}^{\prime}\)), 128.84 (C3\({}^{\prime}\), C5\({}^{\prime\prime}\)), 129.67 (C3, C5), 130.18 (C4\({}^{\prime\prime}\)), 130.33 (C2, C6), 131.19 (C4), 132.46 (C3\({}^{\prime}\), C5\({}^{\prime}\)), 134.19 (C1\({}^{\prime\prime}\)), 146.03 (C1), 148.11 (N=CH), 151.21 (C1\({}^{\prime}\)), 162.01 (C=O). MS (ESI) _m_/_z_ calcd. for C21H18N2O4S [M]+ 394.09, found 393.92.