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

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

Volume: 13 Issue: 5

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

Affiliation:

• Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, Thessaloniki 54124,Greece

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

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.

Cite this article as:

Tziona Paraskevi, Theodosis-Nobelos Panagiotis and Rekka A. Eleni*, Medicinal Chemistry Approaches of Controlling Gastrointestinal Side Effects of Non-Steroidal Anti-Inflammatory Drugs. Endogenous Protective Mechanisms and Drug Design, Medicinal Chemistry 2017; 13 (5) . https://dx.doi.org/10.2174/1573406413666170209123433

DOI https://dx.doi.org/10.2174/1573406413666170209123433	Print ISSN 1573-4064
Publisher Name Bentham Science Publisher	Online ISSN 1875-6638