New Schiff base derivatives were designed, and the computational methods were used to predict their
anti-inflammatory activity in silico against cyclooxygenase-2 (COX-2) and tubulin polymerization inhibition (TPI)
protein to expect their anticancer activity. The developed compounds [S] & [S1-S6] were designed by incorporating
thiadiazole moiety into indomethacin the well-known anti-inflammatory drug. Computational approaches, such as
ADME studies, were done by using the SwissADME server used to predict the pharmacokinetics of the new
compounds. The outcomes demonstrated that all compounds fulfilled the Lipinski rule of five (RO5), except for
compound [S4]. Furthermore, using the GOLD suite program (v. 2021.3.0), to evaluate the selectivity of designed
compounds towards the COX-2 and tubulin polymerization proteins. Docking studies for ligand interactions with
COX-2 protein predict potential activity for compounds (S2, S4, S5) interacting with amino acids in the active pocket
with higher PLP fitness values than the reference (Flurbiprofen and Indomethacin). Moreover, for tubulin inhibition,
the compounds (S1, S4, S5) exceed the reference ligand colchicine in terms of PLP fitness values. As a result,
compounds (S4 & S5) show good impacts on both proteins COX-2 and TPI. The findings highlight the compounds'
relevance as promising lead choices for cancer therapy associated with inflammation, which might help researchers
develop and synthesize more effective candidates in the future. The research also proposed that the identified
substances be investigated in vivo and in vitro to confirm the computer findings.
Key Words: Inflammation, Indomethacin, ADME, GOLD, Thiadiazole.