Abstract
The main objective of this work was to synthesize novel compounds with a
benzo[de][1,2,4]triazolo[5,1-a]isoquinoline scaffold by employing (dioxo-
benzo[de]isoquinolin-2-yl) thiourea as a building block. Molecular docking was
conducted in the COX-2 active site to predict the plausible binding mode and
rationalize the structure–activity relationship of the synthesized compounds.
The structures of the synthesized compounds were confirmed by HREI-MS, and NMR
spectra along with X-ray diffraction were collected for products 1 and 5.
Thereafter, anti-inflammatory effect of molecules 1–20 was evaluated in vivo
using carrageenan-induced paw edema method, revealing significant inhibition
potency in albino rats with an activity comparable to that of the standard
drugs indomethacin. Compounds 8, 9, 15 and 16 showed the highest anti-
inflammatory activity. However, thermal sensitivity-hot plat test, a
radiological examination and motor coordination assessment were performed to
test the activity against rheumatoid arthritis. The obtained results indicate
promising anti-arthritic activity for compounds 9 and 15 as significant
reduction of the serum level of interleukin-1β [IL-1β], cyclooxygenase-2
[COX-2] and prostaglandin E2 [PGE2] was observed in CFA rats.