Search Results (5)

Background/Objectives: Thiadiazine thione (THTT) has gained significant interest owing to its pharmacological potentials, particularly its antiparasitic and anti-inflammatory properties. Leishmaniasis is a clinical syndrome caused by infection with Leishmania species and is associated with an inflammatory response and nociception. The available treatments against leishmaniasis are inadequate, as they are associated with high cost, toxicity, and increased resistance. Methods: In the current study, the antileishmanial potential of five Thiadiazine thione derivatives (C1–C5) was evaluated in vivo against Leishmania tropica. Experiments were performed on BALB/c mice infected with promastigotes and treated with THTT derivatives for 15 days. Additionally, the derivatives were evaluated for their anti-inflammatory, antinociceptive, antipyretic, and antisedative properties using standardized models, including carrageenan-induced paw edema, acetic acid-induced abdominal writhes, yeast-induced fever, and white wood apparatus, respectively. Results: Of the tested derivatives, C5 exhibited the most promising results, with a 61.78% reduction in lesion size and significant decrease in parasite load. Among the derivatives, C1 showed the highest anti-inflammatory activity, with 63.66% inhibition in the paw edema test at the 5th hour post treatment. In the antipyretic assay, C1 and C5 were able to reduce body temperature to a normal level within 1 h of treatment. Furthermore, compounds C4, C2, and C1 showed high nociceptive activity, while C1 and C5 demonstrated the most notable antisedative effects (94 ± 2 and 92 ± 1, respectively), outperforming the standard drug diazepam (13 ± 1). Conclusion: These in vivo findings suggest that THTT derivatives have the potential to serve as a template for developing leishmanicidal drugs, with added anti-inflammatory and analgesic properties. Full article

Alzheimer’s disease (AD) is the most common neurodegenerative disorder, marked by cognitive impairment. Currently, the available treatment provides only symptomatic relief and there is a great need to design and formulate new drugs to stabilize AD. In the search for a new anti-Alzheimer’s drug, 3,5-bis(2-hydroxyethyl)-1,3,5-thiadiazinane-2-thione (THTT), a tetrahydro-2H-1,3,5-thiadiazine-2-thione derivative, was investigated against a scopolamine-induced Alzheimer’s model. The selected test compound was administered intraperitoneally in three doses (15 mg/kg, 30 mg/kg, and 45 mg/kg). The test compound exhibited an IC50 value of 69.41 µg/mL, indicating its ability to inhibit the acetylcholinesterase enzyme. An antioxidant DPPH assay revealed that the IC50 value of the test compound was 97.75 µg/mL, which shows that the test compound possesses antioxidant activity. The results of behavior tests including the Y-maze and elevated plus maze (EPM) show that the test compound improved short-term memory and spatial memory, respectively. Furthermore, in the Morris water maze (MWM) and light/dark model, the test compound shows improvements in learning and memory. Moreover, the results of histological studies show that the test compound can protect the brain against the harmful effects of scopolamine. Overall, the findings of our investigation suggest that our chosen test compound has disease-modifying and neuroprotective activities against the scopolamine-induced Alzheimer’s model. The test compound may be beneficial, subject to further elaborate investigation for anti-amyloid disease-modifying properties in AD. Full article

Malaria is a parasitic infection caused by a protozoon of the genus Plasmodium, transmitted to humans by female biting mosquitoes of the genus Anopheles. Chloroquine and its derivates have caused the parasite to develop drug resistance in endemic areas. For this reason, new anti-malarial drugs as treatments are crucial. This work aimed to evaluate the humoral response. with hyper-immune sera, of mice immunized with six derivatives of tetrahydro-(2H)-1,3,5-thiadiazine-2-thione (bis-THTT) by indirect ELISA test. The cross-reactivity between the compounds as antigens and their microbial activity on Gram-positive and Gram-negative bacteria was evaluated. The results of the humoral evaluation by indirect ELISA show that three bis-THTTs react with almost all of the above. Besides, three compounds used as antigens stimulate the BALB/c mice’s immune system. The best combination of two antigens as a combined therapy displays similar absorbances between the antigens in the mixture, showing similar recognition by antibodies and their compounds. In addition, our results showed that different bis-THTT presented antimicrobial activity on Gram-positive bacteria, mainly on Staphylococcus aureus strains, and no inhibitory activity was observed on the Gram-negative bacteria tested. Full article

The hetero-Diels-Alder reactions of in situ-generated azoalkenes with thioketones were shown to offer a straightforward method for an efficient and regioselective synthesis of scarcely known N-substituted 1,3,4-thiadiazine derivatives. The scope of the method was fairly broad, allowing the use of a series of aryl-, ferrocenyl-, and alkyl-substituted thioketones. However, in the case of N-tosyl-substituted cycloadducts derived from 1-thioxo-2,2,4,4-tetramethylcyclobutan-3-one and the structurally analogous 1,3-dithione, a more complicated pathway was observed. By elimination of toluene sulfinic acid, the initially formed cycloadducts afforded 2H-1,3,4-thiadiazines as final products. Advanced DFT calculations revealed that the observed high regioselectivity was due to kinetic reaction control and that the (4 + 2)-cycloadditions of sterically less unhindered thiones occurred via highly unsymmetric transition states with shorter C..S-distances (2.27–2.58 Å) and longer N..C-distances (3.02–3.57 Å). In the extreme case of the sterically very hindered 2,2,4,4-tetramethylcyclobutan-1,3-dione-derived thioketones, a zwitterionic intermediate with a fully formed C‒S bond was detected, which underwent ring closure to the 1,3,4-thiadiazine derivative in a second step. For the hypothetical formation of the regioisomeric 1,2,3-thiadiazine derivatives, the DFT calculations proposed more symmetric transition states with considerably higher energies. Full article

In order to investigate the effect of the optical properties of the 5-substituent on the stability and the antihngal activity of tetrahydro-2H-1,3,5-thiadizine-2-thione (THTT) moiety, optical isomers and racemic mixture of phenylalanine were incorporated in the 5^th position of THTT to afford derivatives 2a-g. Chemical and enzymatic stability of these derivatives were studied in vitro in aqueous buffer solution of pH 7.4, physiological pH, and 80% human plasma at 37°C using HPLC. The chemical and enzy'matic degradation rates of the tested compounds revealed that the optical properties of the 5-substituent of THTT moiety have no role on their stability at the investigated media. However, the chemical nature of the 3-substiuents has a significant effect on their chemical and enzymatic liability as 3-aralkyl derivatives, 2f and 2g , were the least stable compounds under the investigation conditions. Solid state stability of these derivatives was studied using Differential Scanning Calorimetry (DSC). In spite of the distinguished DSC curves of the racemic cornpounds from that of the corresponding single optical isomers no constant pattern of their thermal stability was observed. The antifbngal activity of 2a-g, was investigated in vitro against Cnndida albicans, C. parasilosis and C. stellatoidea using tube dilution method. No role for the optical properties of the tested compounds on their antifungal activity was observed. The utmost antihngal activity revealed by compound 2g which has 3-phenethyl substituent. Moreover, 2g has the highest lipophilicity and the most susceptible compound for both chemical and enzymatic degradations. Full article