Synthesis, Characterization, and Anti-Cancer Activity of Some New N'-(2-Oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazones Derivatives

El-Faham, Ayman; Farooq, Muhammad; Khattab, Sherine N.; Abutaha, Nael; Wadaan, Mohammad A.; Ghabbour, Hazem A.; Fun, Hoong-Kun

As a prototype 1 H-NMR of 4g showed multiple peaks at δ 0.86-0.89, 1.27-1.29, 1.40-1.44, 1.56-1.60 ppm, and a broad singlet at δ 2.51 ppm corresponding to the valporic acid moiety (2 CH3, 4 CH2, and CH, respectively). Also, two triplet peaks were observed at δ 3.77 and 4.20 ppm corresponding to the two methylene group (CH2-CH2Br), respectively. The observed peaks in the aromatic region at δ 7.18 (t, 1H, Ar-H), 7.32 (d, 1H, Ar-H), 7.53 (t, 1H, Ar-H), and 7.88 (brs, 1H, ArH) are related to the isatin moiety, while the broad singlet peak at δ 12.28 ppm is related to the NH. The 13 C-NMR of 4g showed peaks at δ 14.5, 20.6, 29.9, 35.3, 39.7, 42.2, and 46.5 ppm, corresponding to the valporic acid moiety and the two methylene groups, in addition to seven peaks related to the aromatic carbons and imino function group. The two peaks at δ 169.8 and 176.0 ppm corresponded to the carbonyl groups of the isatin moiety and the hydrazide group, respectively. It is expected that compound 4g could adopt two different geometrical isomers (Z and E) as shown in Figure 2A . Therefore, it is considered worthwhile to model the compounds using molecular mechanics MM2 calculations. In addition, quantum chemical calculations were carried out with the GAUSSIAN 98 suite of programs. Geometry optimizations were carried out using the DFT level (B3LYP/6-31G **) of theory to assess the relative stability of the Z and E isomeric species. Calculated relative energies of 4g Z and E isomers are −3585.4860873 au and 3585.4635100 au, respectively. Computed energies indicate the stability of the Z isomer over the E one by 0.0225773 au (14. 1675 kcal/mol) ( Figure 2B ). The X-ray single crystal structure determination of compound 4g (CCDC: 996592) confirmed that the structure exists in the Z-conformer rather than the E-conformer ( Figure 3 ). The details of data collection and structure refinement are listed in Table 1 , and the X-ray structures are shown in Figure 3 . Compound 4g crystallized from ethanol in the triclinic space group P-1. All bond lengths and angles are in normal ranges [52] .