Medicinal Chemistry Approaches of Controlling Gastrointestinal Side Effects of Non-Steroidal Anti-Inflammatory Drugs. Endogenous Protective Mechanisms and Drug Design

Author(s): Paraskevi Tziona, Panagiotis Theodosis-Nobelos, Eleni A. Rekka*

Journal Name: Medicinal Chemistry

Volume 13 , Issue 5 , 2017

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Graphical Abstract:


Background: Non-steroidal anti-inflammatory drugs are the oldest and most widely used medicines. However, their untoward effects, especially gastrointestinal toxicity, remain the main obstacle to their application. Because of their mechanism of action, cycloxygenase (COX) inhibition, in combination with the weekly acidic character of most of them, major protective mechanisms of the gastrointestinal system are suppressed and deregulated.

Objective: In this review, several compounds designed to retain anti-inflammatory activity, but devoid of gastrointestinal side effects, are presented. Thus, gastro-protective drugs, selective COX-2 inhibitors, nitric monoxide- and hydrogen sulphide-releasing agents, prodrugs, lipoxygenase (LOX) inhibitors and dual COX/LOX inhibitors are presented. Their mechanism of action, as well as their advantages and disadvantages are discussed.

Conclusion: Efforts, aiming to the development of safe non-steroidal anti-inflammatory agents, are evolving, however there are still several problems concerning gastro-protection to be efficiently solved, thus, design of effective and safe agents for the treatment of inflammatory conditions still remains a major challenge.

Keywords: Gastrointestinal toxicity, non-steroidal anti-inflammatory drugs, gastroprotective mechanisms, molecular modifications, NO donors, H2S releasing agents, COX/LOX inhibitors.

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Article Details

Year: 2017
Published on: 09 February, 2017
Page: [408 - 420]
Pages: 13
DOI: 10.2174/1573406413666170209123433
Price: $65

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