Examining barbiturate scaffold for the synthesis of new agents with biological interest

被引：15

作者：

Katsamakas, Sotirios ^{[1
]}

Papadopoulos, Anastasios G. ^{[2
]}

Kouskoura, Maria G. ^{[3
]}

Markopoulou, Catherine K. ^{[3
]}

Hadjipavlou-Litina, Dimitra ^{[1
]}

机构：

[1] Aristotle Univ Thessaloniki, Fac Hlth Sci, Sch Pharm, Dept Pharmaceut Chem, Thessaloniki 54124, Greece

[2] Aristotle Univ Thessaloniki, Sch Chem, Lab Appl Quantum Chem, Univ Campus, Thessaloniki 54124, Greece

[3] Aristotle Univ Thessaloniki, Fac Hlth Sci, Sch Pharm, Dept Pharmaceut Technol, Thessaloniki 54124, Greece

来源：

FUTURE MEDICINAL CHEMISTRY | 2019年 / 11卷 / 16期

关键词：

anti-inflammatory agents; autotaxin inhibitors; cyclooxygenase inhibitors; DFT study; hybrid barbiturates; lipoxygenase inhibitors; molecular modeling; multitarget compounds; phosphodiesterase inhibitors; pleiotropic agents; ACID-BASED INHIBITORS; RAY CRYSTAL-STRUCTURE; AUTOTAXIN EXPRESSION; HYBRID MOLECULES; DRUG DISCOVERY; DERIVATIVES; CYCLOOXYGENASE; OPTIMIZATION; REVEALS; DOCKING;

D O I：

10.4155/fmc-2018-0541

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Aim: Barbiturates have a long history of being used as drugs presenting wide varieties of biological activities (antimicrobial, anti-urease and antioxidant). Reactive oxygen species are associated with inflammation implicated in cancer, atherosclerosis and autoimmune diseases. Multitarget agents represent a powerful approach to the therapy of complicated inflammatory diseases. Results: A novel series of barbiturates has been synthesized and evaluated in several in vitro assays. Compound 16b (lipoxygenases inhibitor, 55.0 mu M) was found to be a cyclooxygenase-2 inhibitor (27.5 mu M). Compound 8b was profiled as a druglike candidate. Conclusion: The barbiturate core represents a new scaffold for lipoxygenases inhibition, and the undertaken derivatives show promise as multiple-target agents to combat inflammatory diseases.

引用

页码：2063 / 2079

页数：17

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