Steroidal Indoxyls: Evaluation of Pka Values and Anti-inflammatory Activity

Abstract

Three steroidal indoxyls, 3-oxo-16,17-seco-16-nor-1,4-androstadien-15-(7’methoxy-2-indoxyliden)17-oic acid, 1-(2’-indoxyliden)-2-nor-1,2-secocholestan-3oic acid and 1-(5’- chloro-2-indoxyliden)-2-nor-1,2-secocholestan-3-oic acid were synthesized and screened for anti-inflammatory activity. Their pKa values were also determined using a solubility method. The first compound, 3-oxo-16,17seco-16-nor-1,4-androstadien-15-(7’-methoxy-2-indoxyliden) 17-oic acid, had an ED50 value of 15.3 mg/kg and a pKa of 7.09. The cholestane derivative, 1-(2’indoxyliden)-2-nor-1,2-secocholestan-3-oic acid, and its chloro analogue 1-(5’chloro-2-indoxyliden)-2-nor-1,2-secocholestan-3-oic acid had ED50 values of 16.2 and 22.8 mg/kg, while their pKa values were 6.56 and 7.07, respectively, suggesting that these compounds are relatively weak acids.