Synthesis, X-ray Structure, Hirshfeld, DFT Conformational, Cytotoxic, and Anti-Toxoplasma Studies of New Indole-Hydrazone Derivatives.

The hydrazones -, were synthesized from the reaction of indole-3-carbaldehyde and nicotinic acid hydrazide, isonicotinic acid hydrazide, and benzoic acid hydrazide, respectively. Their structures were confirmed using FTIR, HNMR, and CNMR spectroscopic techniques. Exclusively, hydrazones and were confirmed using single crystal X-ray crystallography to exist in the form. With the aid of DFT calculations, the most stable configuration of the hydrazones - in gas phase and in nonpolar solvents (CCl and cyclohexane) is the form. Interestingly, the DFT calculations indicated the extrastability of the in polar aprotic (DMSO) and polar protic (ethanol) solvents. Hirshfeld topology analysis revealed the importance of the N…H, O…H, H…C, and π…π intermolecular interactions in the molecular packing of the studied systems. Distribution of the atomic charges for the hydrazones - was presented. The hydrazones - showed a polar character where has the highest polarity of 5.7234 Debye compared to the (4.0533 Debye) and (5.3099 Debye). Regarding the anti-toxoplasma activity, all the detected results verified that had a powerful activity against chronic toxoplasma infection. Compound showed a considerable significant reduction percent of cyst burden in brain homogenates of toxoplasma infected mice representing 49%.