Non‐Steroidal Anti‐Inflammatory Drugs (NSAIDs) in Metal Complexes and Their Effect at the Cellular Level

Abstract

The nonsteroidal anti-inflammatory drugs (NSAIDs) make up a great group of drugs that provide benefits in the prevention of cancers. Coordinated metal ions with NSAIDs provide advantages over the drugs themselves. The metal complexes of NSAIDs display a range of biological activities quite often inaccessible to the original NSAID ligands. NSAIDs-metal complexes have molecular properties different from those of the parent drugs. Thus, if a given NSAIDs-metal complex remains intact in the biological medium its biological target is [a] She is now a Postdoctoral Fellow of the National Scholarships Foundation of Greece-Siemens program with a fellowship of excellence. Her research interests are mainly focused on bioinorganic chemistry and particularly on the evaluation of the anticancer properties of metal complexes by studying their interaction with intracellular molecules. Sotiris K. Hadjikakou was born in Famagusta, Cyprus. He graduated from the Chemistry 3049 dentate, bidentate, or bridge ligands in polynuclear complexes.Compounds of NSAIDs with biometals exhibit better pharmacological activity than free NSAIDs. [11] The structural characteristics, medicinal/veterinary properties, superoxide dismutase (SOD) activity [SOD is an enzyme that catalyzes the dismutation of the superoxide (O 2 -) radical into both ordinary molecular oxygen (O 2 ) and hydrogen peroxide (H 2 O 2 ), thus being involved in the inflammation mechanism], anti-inflammatory, and ulcerogenic effects of Cu-NSAIDs have also been reviewed. [5] The review concluded that the mode of action of the Cu-NSAIDs is similar to that of the traditional NSAIDs and the complexes reduced gastrointestinal toxicity. Moreover, the stabilities of Cu-NSAIDs complexes are a critical determinant of their activity and toxicity. [5] This review summarizes the complexes of NSAIDs: (i) acetylsalicylic acid, diflunisal, salicylic acid (salicylic acid derivatives, Scheme 1), (ii) diclofenac, indometacin, sulindac, tolmetin (arylalkanoic acid derivatives, Scheme 2), (iii) ibuprofen, ketoprofen, Scheme 1. Salicylic acid derivatives.Scheme 2. Arylalkanoic acid derivatives. MicroreviewScheme 3. Arylpropionic acid derivatives (profens).Scheme 4. N-Arylanthranilic acid (fenamic acids). 3050Scheme 5. Other acid derivatives.Scheme 6. Oxicams. MicroreviewScheme 7. Aniline and p-aminophenol derivatives.Scheme 8. Sulfonamides. Discussion Metal Complexes of NSAIDs Exhibiting Anti-Inflammatory or Analgesic ActivityMn II -, Fe II -, Co II -, Ni II -, and Zn II -Schiff base complexes that contain anthranilic acid and aldoses in the Schiff base component are four-coordinate in the anhydrous state with the general formula ML 2 [M = Mn II (1), Fe II (2), Co II (3), Ni II (4), and Zn II (5), Scheme 9]. They were tested for their in vivo biological activities. The stability of the complexes in DMSO solution was confirmed by 1 H NMR spectroscopy. The relative toxicities of the metal complexes were determined with albino Wistar male rats; the LD 50 values followed the trend Ni < Mn < Co < Fe < Zn, w...

Synthesis, characterization, and in vitro effect of the Cu(II) complex with niflumic acid and 3‐picoline on paraoxanase‐I

“…Nonsteroidal anti‐inflammatory drugs (NSAIDs) are the most prescribed drugs in the world as an analgesic, anti‐inflammatory and anti‐inflammatory agents . NSAIDs are responsible for the inhibition of the cyclooxygenase (COX) enzyme (COX‐1 and COX‐2).…”

Aspirin for metal stent in malignant distal common bile duct obstruction (AIMS): study protocol for a multicenter randomized controlled trial

“…Some studies have also provided evidence that aspirin promotes deoxyribonucleic acid (DNA) self-healing by the upregulation of hMLH1, hMSH2, hMSH6, hPMS2 [43], and XRCC expression [44], slowing down gene-mutation accumulation, and protecting normal cell DNA [32,45]. Recent studies have suggested several new aspirin pathways, such as inhibiting the synthesis of prostaglandin E2 (PGE2) [46], controlling the number of circulating platelets and their activity levels to evade several innate anti-tumor effects [47][48][49][50], increasing chemo-agent toxicity, and downregulating cellular drug resistance [51,52]. Since the results of these basic studies have mostly been conducted in vitro and have not been proven in humans, these outcomes cannot be presented as definitive mechanisms of aspirin's effects.…”

Aspirin for metal stent in malignant distal common bile duct obstruction (AIMS): Study protocol for a multicenter randomized controlled trial

“…[38,39] Some studies have also provided evidence that aspirin promotes DNA self-healing by the upregulation of hMLH1, hMSH2, hMSH6, hPMS2, [40] and XRCC expression, [41] slowing down gene mutation accumulation, and protecting normal cell DNA. [29,42] Recent studies have suggested several new aspirin pathways, such as inhibiting the synthesis of PGE2, [43] controlling the number of circulating platelets and their activity levels to evade several innate anti-tumor effects, [44][45][46][47] increasing chemo agent toxicity, and downregulating cellular drug resistance. [48,49] Since the results of these basic studies have mostly been conducted in vitro and have not been proven in humans, these outcomes cannot be presented as definitive mechanisms of aspirin.…”