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Preparation and Evaluation of 99mTc-labeled Tridentate Chelates for Pre-targeting Using Bioorthogonal Chemistry
Published on: February 4, 2017
Biological evaluation of tetracationic compounds based on two 1,4-diazabicyclo[2.2.2]octane moieties connected by
Ekaterina A Burakova1, Irina V Saranina1, Nina V Tikunova1
1Institute of Chemical Biology and Fundamental Medicine, Lavrent'ev Ave. 8, Novosibirsk 630090, Russia.
Abstract:
A series of 1,4-diazabicyclo[2.2.2]octane derivatives differing by linker moiety was evaluated for activity against several strains of both Gram-positive and Gram-negative bacteria including drug-resistant strains, one strain of fungus and influenza virus A/Puerto Rico/8/34 (H1N1). All compounds exhibited high antibacterial activity against all bacteria except Proteus vulgaris. The minimum inhibitory concentrations (MICs) of compound 1c with an o-phenylenebismethyl linker and compound 1e with a propylene aliphatic linker were found to be low and were comparable or better to the reference drug ciprofloxacin for Pseudomonas aeruginosa and Staphylococcus aureus. Additionally, a time-kill assay was performed to examine the bactericidal kinetics. Compounds 1c and 1e displayed rapid killing effects against St. aureus and Ps. aeruginosa after 2h. Furthermore, compounds 1a-c with aromatic linkers and compound 1e showed the highest antiviral activity.
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