Introduction::Histamine, a biological amine, is considered as a principal mediator of
many pathological processes regulating several essential events in allergies and autoimmune diseases.
Numerous derivatives have been developed that strive with histamine at the H1 receptor
and prevent binding of histamine at the H1 receptor, thereby preventing allergic reactions. Molecules
containing a triazole ring fused with six-membered ring systems are found to possess broad
applications in the field of medicine and industry. The present study is an attempt to characterize
the impact of the nature of the substituent introduced at 5 positions of the-4H-1,2,4-triazole-3-thiol
on their capacities to bind with the H1 receptor.
Methods::Molecular docking (PDB ID: 3RZE) revealed that synthesized derivatives and target
proteins were actively involved in binding with Tyr-108, Thr-112, Ala-216, and Phe-432 subunits.
A pharmacophore model, new 5-(4-substituted phenyl)-4-(phenylamino)-4-H-1,2,4-triazole-3-
thiols (5a-5h) were designed and evaluated for H1-blocking activity using isolated segments from
the guinea pig ileum.
Results::According to in silico analysis, all the compounds have a topological polar
surface area (TPSA) less than 140 Å squared, so they tend to a good penetration in cell
membranes. The results show that most of the compounds are non-inhibitors of CYP450
substrates that play a fundamental role in drug metabolism. Compounds 5d
(50.53±12.03), 5h (50.62±12.33) and 7a (55.07±12.41) are more active than others.
Conclusion::Finally, these derivatives were screened for H1 receptor antagonist activity
using guinea pig ileum taking chlorpheniramine maleate as a standard. Most of the
compounds possesses better antihistamine activity.