Biomolecular docking, synthesis, crystal structure, and bioassay studies of 1-[4-(2-chloroethoxy)phenyl]-5-[4-(methylsulfonyl)phenyl]-1H-tetrazole and 2-(4-(5-(4-(methylsulfonyl)phenyl)-1H-tetrazol-1-yl)phenoxy)ethyl nitrate

Abstract

1-[4-(2-Chloroethoxy)phenyl]-5-[4-(methylsulfonyl)phenyl]-1 H -tetrazole ( 2 ) and 2-(4-(5-(4-(methylsulfonyl)phenyl)-1 H -tetrazol-1-yl)phenoxy)ethyl nitrate ( 3 ) have been easily synthesized and their molecular structure have been determined using the X-ray crystallography technique. Both tetrazoles 2 and 3 crystallize in the monoclinic space group P 2 1 /c. The cell parameters determined for tetrazole 2 are a = 25.067 (2) Å, b = 5.2236 (5) Å, c = 13.5324 (13) Å 3 , β = 102.3881 (13)°, V = 1730 (3) Å 3 , and Z = 4. Its structure refines to R 1 = 0.0654 (for 2945 observed reflections [ F o 2 ≥ 2 σ ( F o 2 )]) and w R 2 = 0.1557 (for all 4278 unique reflections). The cell dimensions for tetrazole 3 are a = 26.4012 (10) Å, b = 5.14915 (18) Å, c = 13.2950 (5) Å 3 , β = 92.6313 (16)°, V = 1805.47 (12) Å 3 , and Z = 4. Its structure refines to R 1 = 0.0329 (for 3469 observed reflections [ F o 2 ≥ 2 σ ( F o 2 )]) and w R 2 = 0.0871 (for all 3657 unique reflections). For both structures, the aryl rings at the 1- and 5-positions of the tetrazole rings show no conjugation to the tetrazole group, and intermolecular interactions between adjacent molecules are dominated by weak (2.3–2.7 Å) C–H⋯O and C–H⋯N contacts. The molecular docking studies were carried out to understand the interaction of compounds 2 and 3 within the active site of the cyclooxygenase-2 enzyme, followed by a comparison study with the celecoxib drug as a reference compound. The in vitro bioassay studies of tetrazoles 2 and 3 toward cyclooxygenase-1 and cyclooxygenase-2 enzymes showed that both compounds have no inhibition potency for either enzyme. • The syntheses of two novel tetrazoles. • The crystal structure of tetrazole derivative and nitric oxide release azole. • The molecular docking results toward COX-2/COX-1. • The bioassay results toward COX-2/COX-1. No inhibition potency was found.