Both 2-(N-arylcarbamoyl)methylsulfanyl-3-cyano-5-ethoxycarbonyl-6-methyl-4-(2′-thienyl)pyridines 2a-e and their isomers, 3-amino-2-(N-arylcarbamoyl)-5-ethoxy-carbonyl-6-methyl-4-(2′-thienyl)thieno[2,3-b]pyridines 3a-e were synthesized by reaction of ethyl 3-cyano-1,2-dihydro-6-methyl-4-(2′-thienyl)-2-thioxopyridine-5-carboxylate (1) with the respective N-aryl-2-chloroacetamides in the presence of different basic catalysts. Compounds 3a-e were used as precursors for synthesizing of pyridothienopyrimidinones 4a-e, pyridothienotriazinones 5a-e and tetrahydropyridothienopyrimidinones 6a-c via treatment with triethyl orthoformate, nitrous acid, and/or 4-chlorobenzaldehyde respectively. The photophysical properties of aminothienylthienopyridines 3a-e and tetrahydropyridothieno-pyrimidine-4(3H)-ones 6a-c were studied and the fluorescence data revealed that all selected compounds possess AIE behaviors in solution and in solid state. Most of the prepared compounds were evaluated in vitro for their antibacterial and antifungal activities, and considerable results were obtained. Moreover, the cytotoxic activity of thienopyridines 3a-d against MCF-7 and HepG2 cell lines was evaluated and they showed moderate to very strong activity.

In the recent years, interest in the synthesis of diclofenac derivatives has increased due to their exceptional biological activity. We present here the synthesis of some novel diclofenac derivatives through simple synthetic procedures, where the acylation of carbohydrazide compound 1 with chloroacetyl chloride in dioxane produced the compound 2. Chloroacetohydrazide compound 2 was further subjected to nucleophilic substitution reactions using different nucleophiles such as: hydrazine hydrate, thiosemicarbazide and p-aminobenzenesulfonamide to give the corresponding derivatives 3-5, respectively. Moreover, the reaction of the hydrazinyl compound 3 with active hydrogen species such as: ethyl acetoacetate and acetyl acetone in refluxed ethanol provided the corresponding pyrazolone derivatives 6 and 7, respectively. Furthermore, the reaction of previously reported diclofenac ester 8 with 1,2-diaminoethane gave the amino derivative 9. Finally, condensation reaction of the latter compound with benzaldehyde in dioxan furnished the corresponding Schiff's base compound 10, while its acylation with chloroacetyl chloride in dioxan produced 11. Different spectral (IR, NMR and Mass) and elemental analysis techniques were utilized to explore the structure of the synthesized compounds. All the synthesized compounds were tested for their in-vitro antibacterial activity against different strains of bacteria showing satisfactory results, and molecular docking study was performed to investigate the mode of action.

Simvastatin (SV) is a poorly soluble drug; its oral administration is associated with a significant problem: Myopathy. The present study aims to formulate SV microsponges that have the potential to minimize the myotoxicity accompanying the oral administration of the drug. SV microsponges were prepared by exploiting the emulsion solvent evaporation technique. The % entrapment efficiency (%EE) of the drug approached 82.54 ± 1.27%, the mean particle size of SV microsponges ranged from 53.80 ± 6.35 to 86.03 ± 4.79 µm in diameter, and the % cumulative drug release (%CDR) of SV from microsponges was significantly higher than that from free drug dispersion much more, the specific surface area of the optimized microsponges formulation was found to be 16.6 m²/g revealed the porosity of prepared microsponges. Histological and glycogen histochemical studies in the skeletal muscles of male albino rats revealed that microsponges were safer than free SV in minimizing myotoxicity. These findings were proven by Gene expression of Mitochondrial fusion and fission (Mfn1) & (Fis1) and (Peroxisome proliferator-activated receptor gamma co-activator 1α) PGC-1α. Finally, our study ascertained that SV microsponges significantly decreased the myotoxicity of SV.