Mefenamic acid prodrugs and codrugs - two decades of development

prodrugs are bioreversible derivatives of drug molecules that undergo intermolecular or intramolecular reactions by enzymatic or chemical biotransformation in the human body to give the corresponding active parent drugs and a non-toxic promoiety. Prodrugs have been extensively and successfully used as a chemical tool for modification of the physicochemical, pharmacokinetic as well as pharmacodynamic characteristics of commonly used drugs and new drugs.This mini review focuses on the design, synthesis and pharmacological effects of several prodrugs and codrugs of the non-steroidal anti-inflammatory (NSAIDs), mefenamic acid. Exploitation of the prodrug approach has the potential to achieve a reduction of mefenamic acid GI (gastrointestinal) intolerance, enhance its bioavailability, mask its unpleasant sensation and prolong its duration of action. In addition, utilizing the prodrug concept migh enhance the bioavailability of the counter partner drug of mefenamic acid codrug by increasing its lipophilicity

Mefenamic acid Prodrugs and Codrugs- Two Decades of Development

prodrugs are bioreversible derivatives of drug molecules that undergo intermolecular or intramolecular reactions by enzymatic or chemical biotransformation in the human body to give the corresponding active parent drugs and a non-toxic promoiety. Prodrugs have been extensively and successfully used as a chemical tool for modification of the physicochemical, pharmacokinetic as well as pharmacodynamic characteristics of commonly used drugs and new drugs.This mini review focuses on the design, synthesis and pharmacological effects of several prodrugs and codrugs of the non-steroidal anti-inflammatory (NSAIDs), mefenamic acid. Exploitation of the prodrug approach has the potential to achieve a reduction of mefenamic acid GI (gastrointestinal) intolerance, enhance its bioavailability, mask its unpleasant sensation and prolong its duration of action. In addition, utilizing the prodrug concept migh enhance the bioavailability of the counter partner drug of mefenamic acid codrug by increasing its lipophilicity

Anti-cancer Prodrugs-Three Decades of Design

The conventional old treatment method for cancer therapy is associated with severe side effects along with several limitations. Therefore, searching and developing new methods for cancer became crucial. This mini review was devoted on the design and synthesis of prodrugs for cancer treatment. The methods discussed include targeted prodrugs which are depending on the presence of unique cellular conditions at the desired target, especially the availability of certain enzymes and transporters at these target sites, antibody directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) which is considered one of the important strategies for the treatment of cancer and prodrugs based on enzyme models that have been advocated to understand enzyme catalysis. In this approach, a design of prodrugs is accomplished using computational calculations based on molecular orbital and molecular mechanics methods. Correlations between experimental and calculated rate values for some intramolecular processes provided a tool to predict thermodynamic and kinetic parameters for intramolecular processes that can be utilized as prodrugs linkers. This approach does not require any enzyme to catalyze the prodrug interconversion. The interconversion rate is solely dependent on the factors govern the limiting step of the intramolecular process

Diclofenac Codrugs and Prodrugs-Three Decades of Design

Prodrugs or predrugs are inactive molecules which become active after in vivo conversion to release the active parent drug. The prodrug’s cleavage can be catalyzed by metabolic enzymes or can occur by chemical means without the involvement of enzymes. Prodrugs are designed to improve undesirable physicochemical and pharmacokinetic properties of their parent drugs. Non-steroidal anti-inflammatory (NSAIDs) drugs are among the most commonly used drugs for treatment of pain, inflammation and fever. Despite their frequent use, these agents suffer from gastrointestinal side effects that limit their use for those patients with gastrointestinal conditions. This mini review discusses the design, synthesis and pharmacological effects of prodrugs and codrugs of the non-steroidal anti-inflammatory (NSAIDs) Diclofenac sodium or potassium. It argues that the prodrug approach has the potential to eliminate Diclofenac associated gastrointestinal complications, increases its bioavailability and masks its bitter taste

ANTICANCER PRODRUGS - THREE DECADES OF DESIGN

The conventional old treatment method for cancer therapy is associated with severe side effects along with several limitations. Therefore, searching and developing new methods for cancer became crucial. This mini review was devoted on the design and synthesis of prodrugs for cancer treatment. The methods discussed include targeted prodrugs which are depending on the presence of unique cellular conditions at the desired target, especially the availability of certain enzymes and transporters at these target sites, antibody directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) which is considered one of the important strategies for the treatment of cancer and prodrugs based on enzyme models that have been advocated to understand enzyme catalysis. In this approach, a design of prodrugs is accomplished using computational calculations based on molecular orbital and molecular mechanics methods. Correlations between experimental and calculated rate values for some intramolecular processes provided a tool to predict thermodynamic and kinetic parameters for intramolecular processes that can be utilized as prodrugs linkers. This approach does not require any enzyme to catalyze the prodrug interconversion. The interconversion rate is solely dependent on the factors govern the limiting step of the intramolecular process

DICLOFENAC CODRUGS AND PRODRUGS-THREE DECADES OF DESIGN

Prodrugs or predrugs are inactive molecules which become active after in vivo conversion to release the active parent drug. The prodrug’s cleavage can be catalyzed by metabolic enzymes or can occur by chemical means without the involvement of enzymes. Prodrugs are designed to improve undesirable physicochemical and pharmacokinetic properties of their parent drugs. Non-steroidal anti-inflammatory (NSAIDs) drugs are among the most commonly used drugs for treatment of pain, inflammation and fever. Despite their frequent use, these agents suffer from gastrointestinal side effects that limit their use for those patients with gastrointestinal conditions. This mini review discusses the design, synthesis and pharmacological effects of prodrugs and codrugs of the non-steroidal anti-inflammatory (NSAIDs) Diclofenac sodium or potassium. It argues that the prodrug approach has the potential to eliminate Diclofenac associated gastrointestinal complications, increases its bioavailability and masks its bitter taste