An operationally simple, one‐pot, convenient synthesis, and in vitro anti‐inflammatory activity of some new spirotriazolotriazine derivatives

Abstract

The wide biological actions of triazolotriazine hybrids, benzene‐sulfonamide derivatives, exhibit a good chance of displaying in vitro anti‐inflammatory effects. An operationally simple one‐pot, three‐component, and convenient synthesis method is used toward the synthesis of a series of diverse 2‐(2‐(4‐amino)‐1,3,5‐triazaspiro‐1,4‐dien‐2‐yl) hydrazinyl)‐N‐(4‐sulfamoylphenyl)‐2‐thioxoacetamides, which generated via reaction of 2‐hydrazinyl‐N‐(4‐sulfamoylphenyl)‐2‐thioxoacetamide, cyanoguanidine, and cyclic/acyclic ketones and were characterized by spectral analysis (IR, Nuclear Magnetic Resonance: 1H‐NMR, 13C‐NMR, and elemental analysis). The spirotriazolotriazine derivatives are obtained with up to 95% yield, and their structure–activity relationship was discussed. All compounds were tested for in vitro anti‐inflammatory potential using the inhibition of RBC hemolysis technique and COX inhibition assay. The results from RBC hemolysis technique demonstrated that almost all evaluated compounds exhibited significant in vitro anti‐inflammatory efficacy. More specifically, compounds 7, 8, and 12 have superior membrane stability over indomethacin as a standard drug. At concentrations of 400, 600, 800, and 1000 μg/mL, compound 12 demonstrated highly significant inhibition of RBC hemolysis with 95.2%, 97.3%, 98.9%, and 99.8%, respectively, compared with indomethacin at the same concentrations (94.5%, 97.3%, 98.5%, and 99.3%, respectively). COX assay indicated that compounds 7, 8, and 12 exhibited excellent COX‐2 inhibition percentage (98.51 ± 0.01, 98 ± 0.01, and 98.97 ± 0.06, respectively) at 150 μg/mL using indomethacin (97.3 ± 0.005). Furthermore, an investigation using molecular docking against COX‐2 (pdb ID: 5IKT) was used to analyze the anti‐inflammatory properties of all studied substances. When compared to indomethacin, molecular docking research showed a strong connection with the intended protein and an elevated docking score. According to in vitro anti‐inflammatory action and computational approach, they show promise as a therapeutic candidate for the treatment of inflammatory diseases.

Synthesis, docking and biological evaluation of purine-5-N-isosteresas anti-inflammatory agents

“…As part of our ongoing research into the synthesis of novel heterocycles, [42][43][44][45][46][47][48][49][50][51][52] we prepared in this article a new series of 5-amino-7-(substituted)-N-(4-sulfamoylphenyl)-4,7-dihydro- [1,2,4] triazolo[1,5-a][1,3,5]triazine-2-carboxamidederivatives 4-13 by a new method, a smooth way, one-pot reaction, energy saving (at room temperature), low cost (without catalyst), short period (about 3 h), green solvent (EtOH) method, with high yields (79-93%) and no requirements for toxic chemicals, which follow the green synthesis rules. Thiocarbohydrazide 1 was allowed to react with cyanoguanidine 2 and various aldehydes 3a-3j, namely, furfural, 2-methylbenzaldehyde, cinnamaldehyde, glyoxal, 2-chlorobenzaldehyde, 4-methoxybenzaldehyde, 1naphthaldehyde, 2-hydroxybenzaldehyde, 4(N,N)-dimethyl benzaldehyde, and 3-hydroxybenzaldehyde.…”

New Fe(III), Co(II), Ni(II), Cu(II), and Zn(II) mixed-ligand complexes: stractural, DFT, biological, and molecular docking studies

“…The produced complexes were docked against the antimicrobial target protein in this experiment to determine the relationship between in vitro antimicrobial results and inhibitor binding affinities. By rating a compound's composition, molecular docking studies enable virtual compound screening to determine which molecule has the strongest binding affinity [43]. This approach examines how two molecules, such as a substrate and the active site binding of a target receptor, fit together in three dimensions like jigsaw puzzle pieces [44].…”

Thiadiazole/Thiadiazine Derivatives as Insecticidal Agent: Design, Synthesis, and Biological Assessment of 1,3,4-(Thiadiazine/Thiadiazole)-Benzenesulfonamide Derivatives as IGRs Analogues against Spodoptera littoralis

“…The synthesis of insecticidal drugs has focused a great deal of research on tiny compounds containing a heterocyclic moiety with five or six members, specially 1,3,4-thiadiazole and 1,3,4-thiadiazine. − Because of its physiological activity, 1,3,4-thiadiazole is becoming increasingly important in medicinal chemistry. These agents include those that are anticonvulsant, anti-Alzheimer, anticancer and antitumor, antidiabetic, antiviral, antiplatelet, antituberculosis, carbonic anhydrase inhibitor agents, and diuretic agents .…”