Hybrid organic molecules as antiinflammatory agents; a review of structural features and biological activity

Abstract

Nonsteroidal antiinflammatory drugs (NSAIDs) are widely used for the treatment of pain and inflammation.Some undesirable effects are linked with NSAIDs such as the gastrointestinal tract (GIT) toxicity and cardiovascular disturbances. At present the preparation of a hybrid molecular technique is being used to produce new analgesic and antiinflammatory molecules. Attachment of NSAIDs with nitric oxide and hydrogen sulfide releasing molecules produced some gastroprotective agents with improved analgesic and antiinflammatory activities. Combination of NSAIDs with different biologically active 5-membered, 6-membered, and condensed heterocyclic rings has also led to the formation of some potent molecules. Some of these hybrid molecules, e.g., ibuprofen-thiazole, exhibited less GIT toxicity, while others showed selectivity for COX-2 enzyme, e.g., quinazolinone-pyrimidine and benzothiophene-rhodanine hybrids. COX-2 selectivity was also exhibited by hybrids of NSAIDs with natural molecules such as salicylates-resveratrol, chromoneoxindole, and chrysin-indole-pyrazole. The preparation of new hybrid molecules is significant because they can serve as a lead compound for the discovery and development of safer analgesic and antiinflammatory agents.

Research developments in the syntheses, anti-inflammatory activities and structure–activity relationships of pyrimidines

“…These ndings suggested that the introduction of a 1,2,4-triazolo [1,5-a]pyrimidine scaffold to ursolic acid could afford unexpected enhancement in the anti-inammatory effect of ursolic acid derivatives. Strong IL-6 suppressive effects of compounds (159)(160)(161)(162) were attributed to the presence of -COOH functional group at the 17 position. The incorporation of various substituents (a naphthalene ring, distinctively substituted benzene rings, and a heterocyclic moiety) to the C-2 of ursolic acid enhanced the anti-inammatory effect.…”

“…The FDA also recommends the consumption of a minimum effective dosage of NSAIDs. 161 Consequently, the prime focus of future research must be on the safety of novel pyrimidines-based anti-inflammatory agents. Harmful effects of novel pyrimidine-based anti-inflammatory agents can be kept to a minimum by enhancing their inhibitory potency against proinflammatory mediators, as low dosages of such drugs will be required to cure inflammation.…”

“…Similarly, the preparation of pyrimidines-NSAIDs hybrids might also improve the anti-inflammatory potency of the target compounds. 161 Such anti-inflammatory hybrids can be prepared by the coupling reactions of active pyrimidine derivatives with suitable NSAIDs namely aspirin, ibuprofen, diclofenac, indomethacin, oxaprozin, etodolac, diflunisal, etc. Nevertheless, the safety of pyrimidines-NSAIDs hybrids has to be ensured through in vivo and in vitro studies.…”

Molecular Consortia—Various Structural and Synthetic Concepts for More Effective Therapeutics Synthesis

“…The other organic hybrid compounds with anti-inflammatory properties have been described extensively in the review by Mohsin and Ahmad [ 17 ].…”

New Hybrid Tetrahydropyrrolo[3,2,1-ij]quinolin-1-ylidene-2-thioxothiazolidin-4-ones as New Inhibitors of Factor Xa and Factor XIa: Design, Synthesis, and In Silico and Experimental Evaluation

“…However, epalrestat containing a rhodanine fragment was successfully used to treat diabetes mellitus [25]. For compounds containing fragments of rhodanine, antibacterial activity [26][27][28][29][30][31], fungicidal [26,32], antiviral [30], anti-tuberculosis [33], anti-inflammatory [26,27,34], and anti-cancer [26,27,30,[35][36][37] activities were noted. These compounds can be used in the treatment of diabetes mellitus [25,27], Alzheimer's disease [26,27], and a number of other diseases [38,39].…”