Synthesis, Molecular Structure, Anti-Plasmodial, Antimicrobial and Anti-Oxidant Screening of (E)-1-(Phthalazin-1-yl)-1-[(Pyridin-2-yl)Ethylidene]Hydralazine and 1-[2-(1-(pyridine-3- yl)ethylidene)hydrazinyl]phthalazine

Abstract

Two new hydralazine hydrochloride-derived Schiff bases: (E)-1-(Phthalazin- 1-yl)-1-[(Pyridin-2-yl)Ethylidene]Hydralazine (PPEH), and 1-[2-(1-(pyridine- 3-yl)ethylidene)hydrazinyl]phthalazine (PEHP), were synthesized and partially characterized by spectroscopic and crystallographic methods including IR and X-ray. The single-crystal X-ray diffraction (SCXRD) analysis of PEHP indicates that the hydralazine moiety of both ligands possesses the exocyclic C=N bond. Both, PPEH and PEHP were tested as antimicrobials and antiparasites. Just PEHP could be considered as slightly antiplasmodial and antibacterial agent. In effect, PPEH showed low antimicrobial activity against one bacterial strain with Minimum Inhibitory Concentration (MIC) value of 250 μg/ml while PEHP showed very interesting activity against 18 out of 19 bacterial strains with MIC of 31.25 - 250 μg/ml compared to the standard drug, amoxicillin. PPEH and PEHP showed higher reducing activity on ferric ions compared to Vitamin C. On the other hand, both hidrazaline synthetized derivatives showed as better reducing agents than Vitamin C on ferric ions, while again, only the PEHP showed slightly high inhibition of lipid peroxidation using Vitamin C as standard. Regarding their catalase activity, both compounds showed concentration dependent effect, but Vitamin C continued showing a higher stimulatory effect on the enzyme activity. Additionally, while PPEH showed less than 80% inhibition in the preliminary antiplasmodial assay and so was not considered for the dose-response studies, PEHP displayed an inhibition percentage of 83.60% and 50% Inhibitory Concentration (IC50) value of 44.13 μg/mL compared to the standard drug, artemisinin and was classified as slightly active.