Design, Synthesis, in Vitro and in Silico Studies of Benzimidazole‐Linked Oxadiazole Derivatives as Anti‐inflammatory Agents

Abstract

In this study, 24 new benzimidazole‐oxadiazole hybrids were designed and synthesized as anti‐inflammatory agents. It was measured their stabilizing potentials against heat‐induced human erythrocyte membrane hemolysis for anti‐inflammatory activity. Compound 5 w bearing cyclohexyl as R2 group at the 2nd position of oxadiazole ring and 3,4‐dimethoxy phenyl at the 2nd position of benzimidazole showed the highest membrane stabilizing activity with IC50= 0.50 mM. Antioxidant activity screening of compounds synthesized by ABTS and DPPH radical scavenging assay methods was performed. Molecular docking studies of all compounds were performed against COX‐1 and COX‐2 with Glide XP. Moreover, to examine the protein‐ligand stability of the most active compound 5 w, molecular dynamics simulations of 100 ns duration were performed with COX‐1 and COX‐2 using Gromacs.

An Experimental and Theoretical Study of the Conformational Stability of Triazinone Fleximers: Quantitative Analysis for Intermolecular Interactions

“…Compound 1 crystallized in a monoclinic crystal system with a P21/c space group having a, b and c values of 10.0004 (19)10.5644 (19), and 20.5644 (3) Å, respectively (Table 1). Compound 1 possesses a somewhat folded conformation, and is stabilized by intramolecular CÀ H⋯O and CÀ H⋯N interactions (Table 2).…”

“…The selection of these heteroaromatic cores can be explained as these molecules have shown different biological properties; for example, triazine derivatives have promising cytostatic activity in vitro and may be used as potential leads for the development of new anti‐cancer drugs, antidiuretic, neurodepressant, potential antitumor agents, [14–15] antimicrobial activity [16] and antimalarial activity [17] . Benzimidazole derivatives have been reported for anticancer efficacy, [18] potential antitumor activity, [19] anti‐inflammatory activity, [20] anticonvulsant activity [21] . The phthalimide derivatives have been reported for anticancer activity, [22] anti‐inflammatory, [23] antiproliferative, [24] in vitro anti antibacterial activity [25] …”

Evaluation of the Chemical Composition, Antioxidant and Antidiabetic Activity of Rhaponticoides iconiensis Flowers: Effects on Key Enzymes Linked to Type 2 Diabetes In Vitro, In Silico and on Alloxan-Induced Diabetic Rats In Vivo

“…Redocking was performed with the cocrystal ligand acarbose Glide SP carried by each structure, and the maximum common structure RMSD value between the natural pose and docking pose was measured as 2.216 Å for 1B2Y and 1.429 Å for 5NN8 [ 41 ]. In general, values below 3 Å may indicate that the docking study is making a correct guess [ 22 , 42 ]. In Table 6 , the compounds and docking scores of acarbose with α-amylase and α-glucosidase and protein–ligand interaction details are given.…”

“…As in our previously reported studies [ 19 , 20 ], the MD simulation was performed using Gromacs 2021.2 version [ 21 ]. The necessary input files for the MD of the protein–ligand complexes obtained from the glide ligand docking study were created using the CHARMM-GUI server ( accessed on 23 September 2022) [ 22 , 23 , 24 ]. The Triclinic water box was created with the TIP water model at 10 Å from the protein–ligand complex and neutralized by adding 0.15 M KCl.…”

Vanillin-Based Indolin-2-one Derivative Bearing a Pyridyl Moiety as a Promising Anti-Breast Cancer Agent via Anti-Estrogenic Activity

“…The stability of the compound 6j protein–ligand complex with the estrogen receptor obtained by Glide SP molecular docking was tested by molecular dynamics simulation using Gromacs v2021.2. − The files required for molecular dynamics such as solvation of the protein–ligand complex and neutralization by adding 0.15 M KCl were created with the CHARMM-GUI server () . Topology files of the protein and ligand were created using Amber FF99SB. , Molecular dynamics simulation was carried out at 300 K and 1 atm pressure.…”