There is evidence supporting continued investigation of catechol-flavones and catechol-flavonols for the treatment of neurodegenerative diseases. The compound 7,8-dihydroxyflavone (7,8-DHF) has shown efficacy in preclinical models of Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotropic lateral sclerosis. The catechol-flavonols, fisetin and quercetin, have also exhibited neuroprotection in models of these diseases. For flavonoids to be effective as oral medications for brain disorders, they must be absorbed through the small intestine, delivered through the blood stream and transported across the blood-brain barrier. The logarithm of the 1-octanol/water partition coefficient (LogP) is the most commonly used descriptor for predicting the absorption, delivery, metabolism and excretion (ADME) properties of drugs. Due to problems with self-association, decomposition, and low aqueous solubility, accurate LogP values are hard to measure for complex flavonoids. Simple catechol-flavones were used to measure the positional effect of the catechol group on LogP. Flavone, 7,8-DHF, 5,6-dihydroxyflavone, 6,7-dihydroxyflavone, 2’,3’-dihydroxyflavone, 3’,4’-dihydroxyflavone and 3,2’-dihydroxyflavone (3,2’-DHF) were assayed using a modified “shake-flask” method with detection by UV absorbance. Measured LogP values were generally in between those predicted by the ACD/Labs Percepta Platform and those calculated by the Abraham General Solvation Equation. For each compound, the reverse-phase chromatographic retention factor (k’) was determined using an octadecyl-silane (ODS) column with an acidic methanol/water mobile phase. A good correlation between Logk’ and LogP was obtained. The 1-octanol/aqueous buffer (pH=7.4) distribution coefficient (LogD) was also determined for each compound. Good correlations between Logk’ and LogD were obtained; however, 3,2’-DHF exhibited a very low LogD value. This result is consistent with a pKa value near 6.0 for 3,2’-DHF that confers ionic character at the physiological pH of 7.4.

Comparison of measured and calculated partition coefficients and distribution coefficients for catechol flavones

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.