Abstract
1. In all, 27 compounds related chemically to phenanthrolines were investigated for their ability to stimulate electrogenic chloride secretion in murine colonic epithelia under short circuit current conditions. A total of 11 compounds, not previously examined, were shown to have substantial activity. Cumulative concentration - response relations were obtained in the presence of amiloride to inhibit electrogenic sodium absorption and Ba(2+) to prevent potassium secretion. 2. Single- or double-ring substitutions in 1,10 phenanthroline (EC(50)=612 microM) produced only modest increases in affinity of between 0.7- and 2.1-fold. 3. Naphthalenes with either one or two ring nitrogens showed some activity but had very low affinity, yet some (e.g. isoquinoline, EC(50)=700 microM) were able to produce maximal responses. 4. Removal of one nitrogen from 1,10-phenanthroline or from 4,7-phenanthroline gave, respectively, 7,8-benzoquinoline and 5,6-benzoquinoline. These two were the most active compounds found, the EC(50) for 5,6-benzoquinoline being 29 microM. 5. Most concentration - response curves were steep with Hill slopes of approximately 3. At high concentration, some compounds inhibited the response, producing a characteristic bell shape. 6 5,6- and 7,8-benzoquinoline may be useful starting points for the synthesis of more potent agents by the addition of ring substituents.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.