Design and Synthesis of Triazole-Phthalimide Hybrids with Anti-inflammatory Activity

Abstract

Phthalimido-alkyl-1H-1,2,3-triazole derivatives 3a-d and 4a-d were efficiently synthesized using 1,3-dipolar cycloaddition reaction. Anti-inflammatory activity and toxicity studies were performed. The results demonstrated that all the tested compounds reduced carrageenan-induced paw edema and indicated no lethality for toxicity against Artemia salina and acute toxicity in vivo (LD 50 up to 1 g kg 1). Furthermore, the structure of phthalimide linked to phenyl group proved to be more active than the compounds containing benzothiazole moiety. Structural modifications such as removal of the phthalimide group and subsequent acetylation, to exemplify a non-cyclic amide, demonstrate that the phthalimide and triazole moieties are important for design of potent candidates with anti-inflammatory drug proprieties. Docking into the cyclooxygenase-2 (COX-2) confirms the importance of the phthalimide and triazole groups in the anti-inflammatory activity. The histopathological studies showed that the compounds 3a-d and 4a-d did not cause serious pathological lesions liver or kidneys.

Identification of 1,2,3-triazole-phthalimide derivatives as potential drugs against COVID-19: a virtual screening, docking and molecular dynamic study

“…As triazole derivatives, the phthalimide group has been shown to be useful in the formation of hybrid compounds with antiviral activity against HIV (Al-Masoudi et al, 2016), cytomegalovirus and varicella-zoster (Mandi c et al, 2020). Importantly, both triazole and phthalimide derivatives also have relevant anti-inflammatory activity (Assis et al, 2019). Therefore, 1,2,3-triazole-phthalimide hybrids may not only be able to prevent viral replication but also treat the severe form of COVID-19, characterized by an intense inflammatory process called "cytokine storm" (Zhang et al, 2020).…”

Synthesis of 1,4-Biphenyl-triazole Derivatives as Possible 17β-HSD1 Inhibitors: An in Silico Study

“…Many triazole-based derivatives are available as medicines; 5 however, they also have a wide range of important applications in the agrochemical, 6 dendrimer, 7 supramolecular, 8 electrochemical, 9 corrosion retardant, 10 optical brightener, 11 metal chelator, 12 and material fields. 13 Their important biological activities include anticancer, 14 antitumor, 15 anti-HSV-1, 16 antimalarial, 17 antitubercular, 18 antileishmanial, 19 antifungal, 20 antibacterial, 21 antimicrobial, 22 antidiabetic, 23 antihypertensive, 24 anti-inflammatory, 25 anti-Alzheimer, 26 antiepileptic, 27 and anticonvulsant. 28 Their importance in the field of medicinal chemistry is due to high dipole moment, rigidity, and capability to bind with various kinds of enzymes and receptors via weak interactions such as hydrogen bonds, coordination bonds, ion−dipole, dipole−dipole, and cation−π and π stacking interactions when they bind with the biological target.…”

1,2,3- Triazoles: general and key synthetic strategies

“…7 Amidst the numerous categories of heterocyclic compounds, 1H-1,2,3-triazole and their derivatives stand out as they constitute an important class of heterocycles in scientific academic and industrial research. For example, studies involving 1H-1,2,3-triazole derivatives report a number of important biological activities, such as antimicrobial, 8 antiviral, 9 antineoplastic, 10 trypanosomicide, 11 antimalarial, 12 antibacterial, 13 antiinflammatory, 14 antituberculosis 15 and leishmanicidal. 16 These derivatives have also become relevant in bioconjugation strategies 17 and have been extensively used as synthetic intermediates in many industrial applications such as manufacturing of agrochemicals, 18 corrosion inhibitors, 19 photostabilizers 20 and dyes.…”