We made fusion protein of fastatin and FIII 9-10, termed tetra-cell adhesion molecule (T-CAM) that can interact simultaneously with alphavbeta3 and alpha5beta1 integrins, both playing important roles in tumor angiogenesis. T-CAM can serve as a cell adhesion substrate mediating adhesion and migration of endothelial cells in alphavbeta3 and alpha5beta1 integrin-dependent manner. T-CAM showed pronounced anti-angiogenic activities such as inhibition of endothelial cell tube formation, endothelial cell proliferation, and induction of endothelial cell apoptosis. T-CAM also inhibited angiogenesis and tumor growth in mouse xenograft model. The anti-angiogenic and anti-tumoral activity of molecule like fastatin could be improved by fusing it with integrin-recognizing cell adhesion domain from other distinct proteins. The strategy of combining two distinct anti-angiogenic molecules or cell adhesion domains could facilitate designing improved anticancer agent of therapeutic value.
Angiogenesis Inhibitors/chemistry/*pharmacology ; Animals ; Antineoplastic Agents/chemistry/*pharmacology ; Base Sequence ; Benzocaine/chemistry/*pharmacology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Chloramphenicol/chemistry/*pharmacology ; DNA Primers ; Drug Combinations ; Factor VIII/chemistry/*pharmacology ; Humans ; Integrin alpha5beta1/*physiology ; Integrin alphaVbeta3/*physiology ; Male ; Mice ; Mice, Inbred BALB C ; Nitrofurazone/chemistry/*pharmacology ; Recombinant Fusion Proteins/chemistry/*pharmacology

A series of new coumarin-based benzotriazole derivatives were successfully synthesized via a multi-step sequence of cyclization, etherification and N-alkylation, and were confirmed by 1H NMR, IR, MS spectra as well as elemental analyses. All these synthesized coumarin compounds were evaluated for in vitro antimicrobial activities against four Gram-positive bacteria, four Gram-negative bacteria and three fungi by two fold serial dilution technique. The bioactive assay showed that all these prepared coumarin benzotriazoles could inhibit the growth of the tested bacterial and fungal strains. Title compounds 11a-11e and 13a-13c were more active than chloromycin on Proteus vulgaris ATCC 6896. Coumarin benzotriazoles 11a and 11b displayed comparable antibacterial efficacy against Staphylococcus aureus ATCC 25923 and Micrococcus luteus ATCC 4698 in comparison with reference drug chloromycin. Compared to fluconazole, compounds 11a-11d displayed stronger inhibition on Aspergillus fumigatus ATCC 96918. Moreover, coumarin-based benzotriazoles in combination with antibacterial chloromycin or antifungal fluconazole, showed notable antimicrobial efficacy with less dosage and broader antimicrobial spectrum. More importantly, fluconazole-insensitive A. fumigatus and methicillin-resistant Staphylococcus aureus N 315 (MRSA) were sensitive to these combined drugs.
Anti-Bacterial Agents ; chemical synthesis ; chemistry ; pharmacology ; Antifungal Agents ; chemical synthesis ; chemistry ; pharmacology ; Aspergillus fumigatus ; drug effects ; Chloramphenicol ; pharmacology ; Coumarins ; chemical synthesis ; chemistry ; pharmacology ; Drug Synergism ; Fluconazole ; pharmacology ; Fungi ; drug effects ; Gram-Negative Bacteria ; drug effects ; Gram-Positive Bacteria ; drug effects ; Methicillin-Resistant Staphylococcus aureus ; drug effects ; Staphylococcus aureus ; drug effects ; Triazoles ; chemical synthesis ; chemistry ; pharmacology

Seventy Escherichia coli isolates recovered from diseasedchickens diagnosed with colibacillosis in Henan Province,China, between 2004 and 2005 were characterized forantimicrobial susceptibility profiles via a broth doublingdilution method. Overall, the isolates displayed resistanceto trimethoprim-sulfamethoxazole (100%), oxytetracycline(100%), ampicillin (83%), enrofloxacin (83%), and ciprofloxacin(81%), respectively. Among the phenicols, resistance wasapproximately 79% and 29% for chloramphenicol andflorfenicol, respectively. Molecular detection revealed thatthe incidence rates of the floR, cmlA, cat1, cat2 and cat3were 29, 31, 16, 13, and 0%, respectively. Additionally,10% of the isolates were positive for both floR and cmlA.As these antimicrobial agents may potentially inducecross-resistance between animal and human bacterialpathogens, their prudent use in veterinary medicine ishighly recommended.
Animals ; Anti-Bacterial Agents/*pharmacology ; *Chickens ; China/epidemiology ; Chloramphenicol/pharmacology ; DNA, Bacterial/chemistry/genetics ; Drug Resistance, Multiple, Bacterial ; Escherichia coli/*drug effects/growth & development ; Escherichia coli Infections/epidemiology/microbiology/*veterinary ; Microbial Sensitivity Tests/veterinary ; Polymerase Chain Reaction/veterinary ; Poultry Diseases/epidemiology/*microbiology ; Thiamphenicol/analogs & derivatives/pharmacology