Design, synthesis, and biological evaluation of new tetrahydropyrimidine derivatives as multitarget anti-inflammatory agents

In an innovative strategy for addressing inflammatory conditions, new 2-oxo-1,2,3,4-tetrahydropyrimidine derivatives were synthesized and subsequently assessed for their multitarget anti-inflammatory effects on various biomarkers, including IL-6, TNF-α, IL-1β, NF-κB, iNOS, MAPK, and ERK, through in vitro experimentation. The presence of LPS was found to significantly increase the levels of IL-6, TNF-α, and IL-1 beta. However, treatment with the tetrahydropyrimidine derivatives, especially compound 4d with an IC 50 value of 0.4-0.69 μM, led to a substantial reduction in these cytokine levels. Furthermore, LPS was observed to upregulate the expression of MAPK and ERK, as well as NF-κB and iNOS, but these were significantly diminished following treatment with the tetrahydropyrimidines, particularly the compound identified as 4d , which exhibited an IC 50 value of 0.2-0.62 μM for NF-κB, iNOS and MAPK. The molecular docking studies conducted on the three enzymes revealed notable binding characteristics and affinities, thereby reinforcing their biological functions. • Novel tetrahydropyrimidine analogs were synthesized for anti-inflammatory action. • Compound 4d notably reduced IL-6, TNF-α, and IL-1β levels (IC 50 : 0.4-0.69 μM). • Compound 4d showed potent inhibition (IC 50 : 0.2-0.62 μM) for NF-κB, iNOS, and MAPK. • The molecular docking study proved for enzyme binding and biological relevance.