Virtual screening of 2,3-disubstituted-4(3H)-quinazolinones possessing benzenesulfonamide moiety for COX-2 inhibitor
نویسندگان
چکیده
COX inhibitors which selectively inhibits the inducible COX-2 is an oenzyme that causes inflammation. They are clinically effective anti-inflammatory agents with less gastrointestinal and renal toxicity. However, they lack anti-thrombotic activity and hence lead to increased incidences of adverse cardiovascular trombotic events such as myocardial infarction. Therefore, there is still a need to develop better therapeutic effect and tolerability COX-2 inhibitor. The majority of COX-2 inhibitors are diaryl heterocycles. For optimum COX-2 selectivity and inhibitory potency a -SO(3)CH(3) or a- SO(2)NH(2) substituent at the para-position of phenyl ring was essential. A wide variety of heterocycles can serve as central ring system of the diaryl heterocycles structures. We report the screening of various 2,3-disubstituted-4(3H)-quinazolinones possessing benzenesulfonamide moiety, directly or indirectly bound to the ring system, using the Protein-Ligand ANT System (PLANTS) docking software against the COX-2 enzyme. Various molecular structures of ligands were docked and scored to identify structurally similar ligands to SC-558 (reference ligand) in binding interaction to COX-2 binding site. The results show that 2,3-disubstituted-4(3H)-quinazolinones possess pbenzenesulfonamide moiety at C-2, and phenyl moiety at N-3 binds directly or indirectly to the ring system with high binding affinity. The docked ligand has orientations similar to that observed with SC-558 satisfying Lipinski's rule of five.
منابع مشابه
Synthesis of some new 2,3-disubstituted-4(3H)quinazolinone derivatives
Quinazolinones are interesting materials because of their valuable biological effects. In this study some new 2,3-disubstituted-4(3H)quinqzolinone derivatives were synthesized from anthranilic acid in six steps by introducing a new chiral center to the aliphatic side chain of the quinazolinone. In the last step, a single acylation on the hydrazine moiety afforded final compounds. The structures...
متن کاملMicrowave Irradiation Promoted Reactions of Benzoxazin-4-Ones with Primary Amines. Preparation of 4(2=3H)-Quinazolinones
An efficient synthesis of 3-substituted or 2,3-disubstituted 4(3H)-quinazolinones from benzoxazin-4-ones and primary amines under microwave irradiation in unsealed vessels is described.
متن کامل[γ-Fe2O3-HAp-(CH2)3-NHSO3H] nanoparticles as a highly efficient and magnetically separable catalyst for green one-pot synthesis of 4(3H)-Quinazolinones
Quinazolinone derivatives are essential units in a wide range of relevant pharmacophores with a broad spectrum of abilities. Due to their wide range of pharmacological and therapeutic activities including anticonvulsant, anti-inflammatory, hypolipidemic, anticancer, and anti-ulcer, the synthesis of quinazolinone moieties as a privileged class of fused heterocyclic compounds, have received much ...
متن کامل[γ-Fe2O3-HAp-(CH2)3-NHSO3H] nanoparticles as a highly efficient and magnetically separable catalyst for green one-pot synthesis of 4(3H)-Quinazolinones
Quinazolinone derivatives are essential units in a wide range of relevant pharmacophores with a broad spectrum of abilities. Due to their wide range of pharmacological and therapeutic activities including anticonvulsant, anti-inflammatory, hypolipidemic, anticancer, and anti-ulcer, the synthesis of quinazolinone moieties as a privileged class of fused heterocyclic compounds, have received much ...
متن کاملSynthesis and anticonvulsant activity of some new 2-substituted 3-aryl-4(3H)-quinazolinones.
A series of 4(3H)-quinazolinones structurally related to 2-methyl-3-o-tolyl-4(3H)-quinazolinone (methaqualone, 3) were synthesized and evaluated for anticonvulsant activity. Preliminary screening of these compounds revealed that 2-[2-oxo-2-(4-pyridyl)ethyl]-3-aryl-4(3H)-quinazolinones 6l and 8i, 8k, and 8p-r having a single ortho substituent on the 3-aryl group had the most promising anticonvul...
متن کامل