Amiloride Analogs as ASIC1a Inhibitors

Synthesis and preliminary evaluation of amiloride analogs as inhibitors of the urokinase-type plasminogen activator (uPA).

A known side-activity of the oral potassium-sparing diuretic drug amiloride is inhibition of the enzyme urokinase-type plasminogen activator (uPA, K(i)=7 μM), a promising anticancer target. Several studies have demonstrated significant antitumor/metastasis properties for amiloride in animal cancer models and it would appear that these arise, at least in part, through inhibition of uPA. Selectiv...

Piperidinylethanamine Analogs as Anti-HIV-1 Inhibitors

Inhibition of TRPP3 channel by amiloride and analogs.

TRPP3, a member of the transient receptor potential (TRP) superfamily of cation channels, is a Ca2+-activated channel permeable to Ca2+, Na+, and K+. TRPP3 has been implicated in sour tasting in bipolar cells of tongue and in regulation of pH-sensitive action potential in spinal cord neurons. TRPP3 is also present in excitable and nonexcitable cells of other tissues, including retina, brain, he...

Evaluation of second generation amiloride analogs as therapy for cystic fibrosis lung disease.

Epithelial sodium channel (ENaC) blockers have been proposed as a therapy to restore mucus clearance (MC) in cystic fibrosis (CF) airways. The therapeutic effects of the first generation ENaC blocker, amiloride, in CF patients, however, were minimal. Because the failure of amiloride reflected both its low potency and short duration of action on airway surfaces, we investigated whether the incre...

Azastilbene Analogs as Tyrosinase Inhibitors: New Molecules with Depigmenting Potential

This research has been an effort to develop synthetic resveratrol analogs in order to improve the depigmenting potential of natural resveratrol. Six resveratrol analogs were synthesized and tested for tyrosinase inhibitory activity in vitro, by qualitative and quantitative steps. The results showed the analog C as being the most powerful tyrosinase inhibitor (IA50=65.67±0.60 μg/mL), followed by...