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Virtual screening of 2,3-disubstituted-4(3H)-quinazolinones possessing benzenesulfonamide moiety for COX-2 inhibitor.

ABSTRACT: 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.

SUBMITTER: Hayun

PROVIDER: S-EPMC3218419 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Virtual screening of 2,3-disubstituted-4(3H)-quinazolinones possessing benzenesulfonamide moiety for COX-2 inhibitor.

Hayun Yanuar Arry A Hanafi Muhammad M Pws Sumi Hudiyono SH

Bioinformation 20111031 5

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 ar ...[more]

PMID: 22125393

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Project description:We present in this paper a direct and efficient study regarding synthesis and spectral characterization of three series of hybrid quinoline anchored with 4-R-benzenesulfonamide moiety, with potential antimicrobial activity, by using ultrasound (US) irradiation and conventional methods (CV). The synthesis pathway is efficient and direct, in two steps: an initial N-acylation of 8-aminoquinoline followed by metal complexation with variously M2+ metals (Cd2+, Co2+, Cu2+, Ni2+, Pd2+, Zn2+). For both type of reactions, N-acylation and complexation, under US irradiations the synthesis have some undeniable advantages: the most relevant being the higher yields, a dramatically decrease for reaction time (with about 150 (one hundred fifty) folds for complexation) comparative with conventional methods (CV) (therefore the spent energy decrease in the same way), a decrease of the amount of used solvents. Taking into account the above considerations these reactions setup could be appreciated as eco-friendly. The structures of the obtained hybrid quinoline - sulfonamide complexes (HQBSM) were determined by elemental analysis and by using spectral investigations: FT-IR, NMR experiments, and X-ray diffraction (in three cases). The FT-IR and NMR spectra of complexes show a similar spectroscopic pattern for all complexes and fully confirm the proposed structures. The X-ray spectra analyses prove without doubts the structure of metal complexes, indicating that their structure depends essentially by two factors: the nature of metal and the nature of sulfonamide-quinoline moieties. Complexes containing 4-methoxy-benzoyl moiety and Zn2+ (e.g. 6a) are tetra-coordinated while in the Ni2+ complex (e.g. 6e) the metallic ion forms a distorted square-based bi-pyramid. In the complexes containing 4-nitro-benzoyl moiety and Cd2+ (e.g. 5d) the metallic ion forms a triangular bipyramid. The antibacterial and antifungal assay reveal that only hybrid HQBSM complex (4e) (with 4-chlorophenyl moiety and Ni2+ in molecule) have a significant antibacterial activity.

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Virtual screening of 2,3-disubstituted-4(3H)-quinazolinones possessing benzenesulfonamide moiety for COX-2 inhibitor.

Publications

Virtual screening of 2,3-disubstituted-4(3H)-quinazolinones possessing benzenesulfonamide moiety for COX-2 inhibitor.

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