Molecular Docking and Fluorescence Characterization of Benzothieno[3,2-d]pyrimidin-4-one Sulphonamide Thio-Derivatives, a Novel Class of Selective Cyclooxygenase-2 Inhibitors

Abstract

Abstract:The aims of this study were: (i) to explore the structure-activity relationship of some new anti-inflammatory benzothieno[3,2-d]pyrimidin-4-one sulphonamide thio-derivatives 1-11; and (ii) to evaluate the possibility of using the most active compounds as fluorescent probes to determine tumours or their progression. Therefore, to know the precise mechanism by which these compounds interact with cyclooxygenase (COX)-2 enzyme, a molecular docking study was carried out; to assess spectroscopic characteristics, their absorption and emission properties were determined. The results demonstrated that some derivatives of benzothieno[3,2-d] pyrimidine exhibit interesting anti-inflammatory properties related to interactions with active sites of COX-2 and are fluorescent. The antipyrine-bearing compound 4 displayed high COX-2 affinity (ΔG = −9.4) and good fluorescent properties (Φ fl = 0.032). Thus, some members of this new class of anti-inflammatory may be promising for fluorescence imaging of cancer cells that express the COX-2 enzyme. Further in vitro and in vivo studies are needed to confirm this hypothesis.

In Silico Molecular Docking of Xanthone Derivatives as Cyclooxygenase-2 Inhibitor Agents

“…Clinical data shows that, although COX-2 plays a role in the repairment of injury, excessive expression of this enzyme will promotevarious pathological processes, including carcinogenesis and cancer growth [3]. COX-2 enzymes are found to be highly expressed in a number of inflammatory processes and tumours, such as inflammatory bowel disease (IBD) and colon cancer, whereas it is minimal or undetected at the normal colon cell [4].…”

Synthesis and evaluation of antitumor activity of new 4-substituted thieno[3,2-d]pyrimidine and thienotriazolopyrimidine derivatives

“…Also, 2-(phenylsulfonyl)methyl-thieno [3,2-d]pyrimidine derivatives act as novel HIV-1 replication inhibitors (16). Further, benzo-thieno [3,2-d]pyrimidin-4-one sulphonamide thio-derivatives act as inhibitors of COX-2, iNOS and ICAM-1 (17). Thieno [3,2-d] pyrimidine derivatives have recently become an important class of chemotherapeutic drugs, notably for the treatment of cancers, such as PI3K inhibitor (18), PI3K and mTOR dual inhibitor (19).…”

“…The deposited precipitate was filtered off and crystallized from dioxane. (17). -To a warm solution of 16 (0.01 mol) in glacial acetic acid (40 mL), 4-phenylenediamine (0.01 mol) was added.…”

“…In addition, compound 12 was used to synthesize thieno [1,2,4] triazolopyrimidine derivatives 14 and 15 and 3-methyl--2-(methyl-sulfonyl)-6-phenyl-thieno [3,2-d]pyrimidin-4(3H)--one (16) through the reaction with the respective reagents. Moreover, the reaction of 16 with 4-phenylenediamine gave 2-[(4-aminophenyl)-amino]-3-methyl-6-phenyl-thieno [3,2-d] pyrimidin-4(3H)-one (17), which reacted with methanesulfonyl chloride to afford N-{4-[(3-methyl-4-oxo-6-phenyl-3H,4H--thieno [3,2-d]pyrimidin-2-yl)-amino]phenyl}-methanesulfonamide (18). The majority of the newly synthesized compounds displayed potent anticancer activity, comparable to that of doxorubicin, on three human cancer cell lines, including the human breast adenocarcinoma cell line (MCF-7), cervical carcinoma cell line (HeLa) and colonic carcinoma cell line (HCT-116).…”

Discovery of a potent cyclooxygenase-2 inhibitor, S4, through docking-based pharmacophore screening, in vivo and in vitro estimations

“…COX-1 is expressed constitutively in almost all mammalian cells and involved in homeostasis, [1][2][3] whereas COX-2 is inducibly expressed and involved in inflammatory processes. 13 Thus, COX-2 is an attractive target to develop anti-inflammatory, antitumor, and antimetastatic therapeutic agents. 7,8 In addition, COX-2 is expressed at high levels in tumors and inflammatory lesions but not in normal cells.…”