The increasing incidence of erythromycin and erythromycin-induced resistance to clindamycin among Staphylococcus aureus (S. aureus) is a serious problem. Patients infected with inducible resistance phenotypes may fail to respond to clindamycin. This study aimed to identify the prevalence of erythromycin and erythromycin-induced resistance and assess for potential inhibitors. A total of 99 isolates were purified from various clinical sources. Phenotypic detection of macrolide-lincosamide-streptogramin B (MLS_B)-resistance phenotypes was performed by D-test. MLS_B-resistance genes were identified using PCR. Different compounds were tested for their effects on erythromycin and inducible clindamycin resistance by broth microdilution and checkerboard microdilution methods. The obtained data were evaluated using docking analysis. Ninety-one isolates were S. aureus. The prevalence of constitutive MLS_B, inducible MLS_B, and macrolide-streptogramin (MS) phenotypes was 39.6%, 14.3%, and 2.2%, respectively. Genes including ermC, ermA, ermB, msrA, msrB, lnuA, and mphC were found in 82.6%, 5.8%, 7.7%, 3.8%, 3.8%, 13.5%, and 3.8% of isolates, respectively. Erythromycin resistance was significantly reduced by doxorubicin, neomycin, and omeprazole. Quinine, ketoprofen, and fosfomycin combated and reversed erythromycin/clindamycin-induced resistance. This study highlighted the significance of managing antibiotic resistance and overcoming clindamycin treatment failure. Doxorubicin, neomycin, omeprazole, quinine, ketoprofen, and fosfomycin could be potential inhibitors of erythromycin and inducible clindamycin resistance.

Novel series of aminopyrimidines bearing a biologically active cyclohexenone 3a–f and oxo-selaneylidene moiety 4, besides selenadiazolopyrimidines (5a–e and 7), were synthesised using 5,6-diaminouracils as starting materials. Compound 3a exhibited strong anti-proliferative activity against three cell lines: HepG-2 (IC₅₀ 14.31 ± 0.83 µM), A-549 (IC₅₀ 30.74 ± 0.76 µM), and MCF-7 (IC₅₀ 27.14 ± 1.91 µM). Also, it was four times more selectively cytotoxic against WI-38 cell lines than doxorubicin. Furthermore, Topoisomerase II (IC₅₀ 4.48 ± 0.65 µM) and HSP90 (IC₅₀ 1.78 ± 0.11 µM) were both strongly inhibited in vitro by 3a. The cell cycle was halted at the G1-S phase, and total apoptotic cells were 65 times more than control Hep-G2 cells. Besides, it increased caspase-3 gene expression, triggering mitochondrial cell death. Molecular docking study indicated that it could bind to Topoisomerase II and HSP90 binding sites in an inhibitory mode. Its geometric properties were investigated using the density functional theory (DFT). Furthermore, compound 3a demonstrated in silico good oral bioavailability. Graphical Abstract

Phosphodiesterase 7A enzyme is one the most recent targets for designing potent anti-inflammatory agents with minimal side effects. Quinazolinones are unique building blocks of wide biological activities. Different Quinazolinones were reported to act as Phosphodiesterase 7A inhibitors anti-inflammatory particularly against choronic inflammation and autoimmune disease. Ultrasound is a green convenient method for synthesis of different heterocyclic ring system that is advantageous in terms of yield and reaction time. Ultrasound was used for one pot synthesis of 3-substituted 6-aryl-dihydroisoindolo[2,1-a]quinazoline-5,11-diones and 3-Aryl quinazoline-2,4(1H,3H)-diones. Seventeen compounds were synthesized in good yields. The synthesized compounds were inspected for in vitro inhibitory activity against phosphodiesterase7A enzyme. Molecular docking was used to study the mode of interaction of all the synthesized compounds into the enzyme phosphodiesterase 7A binding site. Five compounds showed high inhibitory activity of enzyme Phosphodiesterase 7A at micro-molar level compared to reference drug. The compounds showed good recognition at the enzyme binding site in the molecular docking. There was a good agreement between the molecular docking and the biological screening results.

Aim: Thalidomide, a once notorious sedative, is now clinically used as an antitumor agent. We aimed to use it as a lead compound for designing pyrimidine–phthalimide hybrids. Materials & methods: N... Graphical abstract