ABSTRACT
The Human papillomaviruses type 16 E7 oncoprotein is a 98-amino-acid, 11-kilodalton acidic oncoprotein with three conserved portions. Due to its interaction with the pRb-E2F complex, CKII, CKI (mostly p21), and even HDAC1, it possesses strong transformative and carcinogenic qualities that inhibit normal differentiation and cell cycle regulation. Here, we target the E7 oncoprotein using two prior research active compounds: asarinin and thiazolo[3,2-a]benzimidazole-3(2H)-one,2-(2-fluorobenzylideno)-7,8-dimethyl (thiazolo), and valproic acid as a control. We are performing molecular docking followed by molecular dynamic analysis. By acting as competitive inhibitors in the binding site, it was hypothesized that both drugs would inhibit E7-mediated pRb degradation and E7-mediated p21 degradation, resulting in decreased cell cycle progression, immortalization, and proliferation. In addition, we expect that the direct inhibitory action of valproic acid in E7 will target the CKII-mediated phosphorylation pathway necessary for destabilizing p130 and pRb. According to the results of the dynamic simulation, stable interactions exist between every compound. Despite the instability of E7 protein, stability results indicate that both natural chemicals are preferable, with thiazolo outperforming valproic acid.
Subject(s)
Oncogene Proteins, Viral , Uterine Cervical Neoplasms , Female , Humans , Oncogene Proteins, Viral/chemistry , Oncogene Proteins, Viral/metabolism , Molecular Docking Simulation , Human Papillomavirus Viruses , Retinoblastoma Protein , Uterine Cervical Neoplasms/drug therapy , Ligands , Valproic Acid/pharmacologyABSTRACT
Oxazolidinone antibacterial agents, where the N-substituted piperazinyl group of eperezolid was replaced with a N-substituted piperidinyloxy moiety, were synthesized and shown to be active against a variety of resistant and susceptible Gram-positive organisms. The effect of ring size, positional isomerism, and fluorine substitution on antibacterial activity was examined.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Escherichia coli/drug effects , Oxazolidinones/chemical synthesis , Oxazolidinones/pharmacology , Staphylococcus aureus/drug effects , Acetamides/chemistry , Drug Resistance/physiology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Microbial Sensitivity Tests , Oxazoles/chemistry , Piperidines/chemistryABSTRACT
The authors present a case of actinomyces of the tongue indicating initial actinomyces with signs of ulceration possibly neoplastic. A swab from a discharge confirmed actinomycosis. A diagnosis by antibiogram led to a cure of the specific location and the general infection.
