Synthesis and Biological Evaluation of Salicylic Acid Analogues of Celecoxib as a New Class of Selective Cyclooxygenase-1 Inhibitor
作者:Sung-Hwa Yoon、Duk-Yeon Cho、Seoung-ryoung Choi、Joo-young Lee、Dong-Kug Choi、Eunha Kim、Ju-Young Park
DOI:10.1248/bpb.b20-00991
日期:2021.9.1
A series of salicylic acid analogues of celecoxib where the phenylsulfonamide moiety in the structure of celecoxib is replaced by salicylic acid moiety was synthesized and tested for in vitro cyclooxygenase (COX)-1 and COX-2 enzyme inhibition. Among the series, 5-substituted-2-hydroxy-benzoic acid analogues (7a–7h) generally showed better inhibitory activities on both enzymes than 4-substituted-2-hydroxy-benzoic acid analogues (12a–12h). In particular, the chloro analogue 7f which had the highest inhibitory effect (IC50 = 0.0057 µM) to COX-1 with excellent COX-1 selectivity (SI = 768) can be classified as a new potent and selective COX-1 inhibitor. The high inhibitory potency of 7f was rationalized through the docking simulation of this analogue in the active site of COX-1 enzyme.
BCL-2/BCL-XL INHIBITORS FOR USE IN THE TREATMENT OF CANCER
申请人:The Regents of The University of Michigan
公开号:EP2668180B1
公开(公告)日:2018-08-01
Singh, Sunil K.; Saibaba; Koteswar Rao, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2005, vol. 44, # 5, p. 1115 - 1118
作者:Singh, Sunil K.、Saibaba、Koteswar Rao
DOI:——
日期:——
[EN] BCL-2/BCL-XL INHIBITORS AND THERAPEUTIC METHODS USING THE SAME<br/>[FR] INHIBITEURS DE BCL-2/BCL-XL ET MÉTHODES THÉRAPEUTIQUES LES UTILISANT
申请人:UNIV MICHIGAN
公开号:WO2012103059A2
公开(公告)日:2012-08-02
Inhibitors of Bcl-2/Bcl-xL and compositions containing the same are disclosed. Methods of using the Bcl-2/Bcl-xL inhibitors in the treatment of diseases and conditions wherein inhibition of Bcl-2/Bcl-xL provides a benefit, like cancers, also are disclosed.
Structure–Activity Relationships of UTX-121 Derivatives for the Development of Novel Matrix Metalloproteinase-2/9 Inhibitors
Celecoxib, a nonsteroidal anti-inflammatory drug, has been reported to have antitumor and antimetastatic activities, and it has potential for application in cancer treatments. The expression of matrix metalloproteinase (MMP)-2/9 is strongly correlated with cancer malignancy, and inhibition of these MMPs is believed to be effective in improving the antitumor and antimetastatic effects of drugs. We have previously revealed that UTX-121, which converted the sulfonamide of celecoxib to methyl ester, has more potent MMP-2/9 inhibitory activity than celecoxib. Based on these findings, we identified compounds with improved MMP inhibitory activity through a structure–activity relationship (SAR) study, using UTX-121 as a lead compound. Among them, compounds 9c and 10c, in which the methyl group of the p-tolyl group was substituted for Cl or F, showed significantly higher antitumor activity than UTX-121, and suppressed the expression of MMP-2/9 and activation of pro MMP-2. Our findings suggest that compounds 9c and 10c may be potent lead compounds for the development of more effective antitumor drugs targeting MMP.