Synthesis, anti-inflammatory and neuroprotective activity of pyrazole and pyrazolo[3,4-d]pyridazine bearing 3,4,5- trimethoxyphenyl
Abdel-Aziz, Mashooq A. Bhat ● Atallah F. Ahmed ● Zhi-Hong Wen ● Mohamed A. Al-Omar, Hatem A. . 2017
A new series of 3,4,5-trimethoxyphenyl bearing
pyrazole (4a–g) and pyrazolo[3,4-d]pyridazine (5a–g)
scaffolds were synthesized in good yield. The newly synthesized
compounds were characterized on the basis of
elemental and spectroscopic analyses. Their inhibitory
activity against the pro-inflammatory inducible nitric oxide
synthase and cyclooxygenase-2 proteins expression in
lipopolysaccharide-stimulated murine RAW 264.7 macrophages
were assessed and showed various potencies. All
pyrazolo[3,4-d]pyridazine compounds (5a–g) strongly
down regulated lipopolysaccharide inducible nitric oxide
synthase expression to the range of 20.3 ± 0.6–51.3 ± 3.5%
relative to the bioactive pyrazole derivatives 4b, 4c, 4e and
4g. With the exception of inactive compounds 4c and 4d, all
other synthesized compounds inhibited cyclooxygenase-2
expression below 100% in the lipopolysaccharide-stimulated
cells, which being declined maximally to 42.8 ± 1.4% by one of the pyrazolo[3,4-d]pyridazine compounds (5d).
Moreover, the neuroprotective activity of the less cytotoxic
compounds 4b, (4e–g) and (5a–g) were evaluated against 6-
hydroxydopamine (6-OHDA)-induced neuroblastoma SHSY5Y
cell death and exhibited significant (p < 0.05) cell
protection. The pyrazolo[3,4-d]pyridazine compound (5e)
exhibited more than 100% of relative neuroprotection
(110.7 ± 4.3%) with an additional advantage of having the
highest cell viability index (107.2 ± 2.9%).
A thalidomide analog, (4‐(1,3‐dioxo‐1,3‐dihydro‐2H‐isoindol‐2‐yl)‐N′‐[(4‐ethoxyphenyl)
methylidene] benzohydrazide), has been identified as a promising broad‐spectrum anti‐inflammatory…
A new series of 3,4,5-trimethoxyphenyl bearing
pyrazole (4a–g) and pyrazolo[3,4-d]pyridazine (5a–g)
scaffolds were synthesized in good yield. The newly synthesized
…