Synthesis, characterization and evaluation of the antioxidant and antibacterial activities of new polycyclic fused pyrimido-pyridazines and pyridazino-purines

A series of fused pyrimido[4,5-d]pyridazin-2(1H)-one, pyrimido[3’,4’:3,2]pyrimido[5,4-d]pyridazin-10-one, pyridazino[4’,5’:5,6]pyrimido[2,1-i]purine and pyridazino[4’,5’:4,5]pyrimido[2,3-b]purin-4(5H)-one were designed and prepared by condensation of hydrazine with pyrimidinone dicarboxylic acid esters in methanol as a solvent. The in vitro antioxidant potential of the target compounds and their precursors was demonstrated by applying free radical scavenging assays using 1,1-diphenyl-1-picrylhydrazyl (DPPH•) and 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS+•) methods. The synthesized compounds 6b and 7b showed the highest antioxidant activity against DPPH with IC50 of 6.55 and 7.93 μg/mL, respectively, compared to ascorbic acid (IC50 = 5.42 μg/ mL). In addition, compounds 5a and 6b showed a greater ABTS radical scavenging effect than BHT (IC50=75.39 μg/mL). The antibacterial activity of the synthesized compounds was evaluated and compared with Gentamicin. Four bacterial strains were considered: Staphylococcus aureus ATCC-6538, Salmonella typhimurium ATCC-14028 (Gram-positive: G+), Pseudomonas aeruginosa ATCC-9027 and Escherichia coli ATCC-8737 (Gram-negative: G-). Compound 4a showed good activity against Pseudomonas aeruginosa, Staphylococcus aureus and Salmonella typhimurium with inhibition zones of 23, 22 and 21 mm, respectively, compared to gentamicin (23, 25 and 22 mm). These results encourage exploration of new biological evaluations and applications of these compounds.