The free –COOH present in NSAIDs is thought to be responsible for the GI irritation associated with all traditional NSAIDs. Exploitation of mutual prodrugs is an approach wherein the NSAID is covalently bounded to a second pharmacologically active carrier/drug with the ultimate aim of reducing the gastric irritation. In this study some NSAIDs were conjugated with gabapentin via ester bonds using glycol spacers with the expectation of reducing gastric adverse effects and obtaining synergistic analgesic effects. The kinetics of ester hydrolysis were studied in two different non enzymatic buffer solutions at pH 1.2 and 7.4, as well as in 80% human plasma using HPLC with chloroform -methanol as mobile phase. Compounds 9a–c with ethylene glycol spacers showed significant stability at buffer solutions with half lives ranging from about 8–25 h, while the underwent a reasonable plasma hydrolysis (49%–88%) in 2 h. Compound 9d with a propylene glycol spacer shows a higher rate of enzymatic hydrolysis than the corresponding ethylene glycol compound 9c. The result of compounds 9a-c indicate that these compounds may be stable during their passage through the GIT until reaching the blood circulation.

A series of 1,2,4 triazole derivatives (H7-12) have been synthesized by reacting an excess of hydrazine hydrate with carbothioamide derivatives (H1-6). The final compounds (HB1-HB6) were synthesized by reacting the triazole derivatives with mefenamic acid using DCC as a coupling agent. The chemical structures were confirmed by FT-IR, 1H, and 13C-NMR spectra, and some physicochemical properties were determined. The cytotoxicity of the different compounds (HB1-HB6) was evaluated by the MTT assay against two human epithelial cancer cell lines, A549 lung carcinoma and Hep G2 hepatocyte carcinoma, and one normal human cell line WI-38 lung fibroblasts. The mode of cell killing (apoptosis versus necrosis), as well as the effect on cell cycle phases were evaluated via flow cytometry. Additionally, EGFR tyrosine kinase inhibition assay was performed. The results presented in the current study indicate that the six tested compounds exhibited cytotoxicity against both cancer cell lines, and the lowest IC50 was achieved with compound HB5 against Hep G2 cancer cells which was found to be highly selective against cancer cells. HB5-treated Hep G2 cells were arrested at the S and G2/M cell cycle phases. Compound HB5 caused cell killing via apoptosis rather than necrosis, and this was achieved by inhibiting EGFR tyrosine kinase activity needed for cell proliferation, and cell cycle progression. In silico pre-ADMET studies confirmed all final compounds don’t cause CNS side effects, with little liver dysfunction effect.

A series of thiosemicarbazide derivatives of captopril, a well-known angiotensin-converting enzyme inhibitor ACEI, have been synthesized by reaction of hydrazide of captopril with different phenylisothiocyanate substituents. The synthesized compounds were characterized using FTIR, 1HNMR and CHNS analysis. The final derivatives were tested for antiplatelet activity using multiplate analyzer and adenosine diphosphate (ADP), arachidonic acid (AA), and collagen, as platelet aggregation inducers. Among tested compounds, derivative 7 and 10 were the most potent inhibitors of platelet aggregation induced by arachidonic acid, with percent inhibition (97.14±0 and 95.71±2.02) and IC50 (2.7 and 1.21μgml), respectively. Molecular docking study was performed using purino receptor P2Y12, COX-1, and glycoprotein llbllla as the target protein, compound 7 has a potential to become as a lead molecule for COX-1 inhibitor with binding energy (-10.67) Kcal/mol. Also, compound 6 was found as the best inhibitor for the glycoprotein IIa/IIIb with percent inhibition (83.9±2.8), and binding energy (-10.05) Kcal/mol.

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The antibiotic resistant crisis is a worldwide phenomenon that threatens the global health. The misuse and overuse of antibiotics as well as the inadequate development of new antibacterial drugs have all drove the evolution of resistance. Thus, the development and discovery of novel antibacterial agents is a critical field within medicinal chemistry. In this study, a series of novel 1,3,4 thiadiazole derivatives containing imine group was synthesized. The chemical structures had been identified by 1 H-NMR, FT-IR, Elemental Analysis (CHNS), and some physicochemical properties. The antibacterial activity of the synthesized compounds was evaluated against two gram-positive (Staphylococcus aureus, Enterococcus faecalis), and two gram negative (Escherichia coli, Klebsiella pneumonia) bacteria. Among the synthesized compounds, compounds e4, e5, and e6 were found to exhibit good antibacterial activity against the tested bacterial strains.

Objective: Inflammation and pain are normally present concomitantly, which requires using a combination of anti-inflammatory and pain killer medications. This could potentially decrease patient adherence to such combinations. Therefore, there is an urgent need to develop combinations of anti-inflammatory and analgesic therapies. This study is designed to evaluate the analgesic and anti-inflammatory activities of a newly synthetic compound of ibuprofen and gabapentin. Method: The study protocol includes two stages. The first stage: the evaluation of the analgesic effectiveness of tested compounds via using hot plate and acetic acid induced-writhing tests. The second stage: the investigation of the anti-inflammatory activity via using dextran induced- peritonitis, cotton pelt induced- granulomas, and formalin induced- paw edema analyses. Rats were randomly divided into four groups (six rats in each group): Group A (control): rats were orally treated with vehicle (propylene glycol 50 % v/v); Group B: rats were orally treated with ibuprofen (10 mg/ kg); Group C: rats were orally treated with gabapentin (200 mg/ kg); and Group D: rats were orally treated with the synthetic compound (ibuprofen-gabapentin) in dose equivalent to 10 mg/ kg ibuprofen and 200 mg/kg gabapentin. Result: It was found that the newly synthesized compound of ibuprofen and gabapentin has significantly reduced the pain in comparison with control groups. Additionally, this compound has significant anti-inflammatory properties compared to medications admitted to the control group as well. Conclusion: The newly synthesized compound (ibuprofen-gabapentin) demonstrates remarkable analgesic and anti-inflammatory activities in comparison with the conventional compounds.