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4.
Arch Pharm (Weinheim) ; 347(11): 861-72, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25220428

ABSTRACT

A series of substituted 4-oxopyrido[2,3-a]phenothiazine-3-carboxylic acids (6a-d) were prepared via cyclization of the corresponding ethyl 7-(arylthioxy)-8-nitro(or azido)-4-oxoquinoline-3-carboxylates (3a-d/4a-d), followed by hydrolysis of the resultant esters (5a-d). Among these tetracyclics, compound 6a with unsubstituted terminal benzo-ring D was the most active against representative Gram-positive and Gram-negative bacterial strains. These compounds were also active against methicillin-resistant Staphylococcus aureus (MRSA), with very low toxicity to normal cells. Virtual screening using ligand-protein docking modeling predicted that the compounds 6a-d are potential inhibitors of the topoisomerase IV enzyme and that hydrophobic interactions and hydrogen bonds are the major molecular interactions between these compounds and the residues of the active site of topoisomerase IV.


Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Phenothiazines/chemical synthesis , Phenothiazines/pharmacology , Animals , Anti-Bacterial Agents/toxicity , Catalytic Domain , Cell Survival/drug effects , Chlorocebus aethiops , DNA Topoisomerase IV/antagonists & inhibitors , DNA Topoisomerase IV/chemistry , Drug Design , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/growth & development , Gram-Positive Bacteria/drug effects , Gram-Positive Bacteria/growth & development , Hydrogen Bonding , Hydrophobic and Hydrophilic Interactions , Ligands , Molecular Docking Simulation , Molecular Structure , Phenothiazines/toxicity , Protein Conformation , Structure-Activity Relationship , Topoisomerase Inhibitors , Vero Cells
11.
Acta Anat (Basel) ; 115(1): 91-6, 1983.
Article in English | MEDLINE | ID: mdl-6219533

ABSTRACT

The study of the intrinsic innervation of the oesophagus in dogs revealed the presence of capsulated ganglia and scattered neurons in the upper and lower thirds of the organ. The cells were either oval or pyriform with multiple dendrites and ill-defined capsules of pericellular satellites. Furthermore, muscle spindles were detected amidst the obliquely set muscle fibres of the oesophageal muscular coat. Simple motor and plates supplied the striated extrafusal muscle fibres. The submucous nerve plexus contained no ganglia. Its nerve fibres extended to form periacinar and intra-acinar axons to the oesophageal submucous glands. Subjacent to the mucosa, the subepithelial nerve plexus gave intraepithelial free terminals that penetrated the basement membrane to end within the stratified epithelium just beneath its cornified layer.


Subject(s)
Esophagus/innervation , Muscle Spindles/anatomy & histology , Animals , Dogs
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