PABA/NO as an anticancer lead: analogue synthesis, structure revision, solution chemistry, reactivity toward glutathione, and in vitro activity

…, M Cuellar, JR Deschamps, D Parrish…

Index: Saavedra, Joseph E.; Srinivasan, Aloka; Buzard, Gregory S.; Davies, Keith M.; Waterhouse, David J.; Inami, Keiko; Wilde, Thomas C.; Citro, Michael L.; Cuellar, Matthew; Deschamps, Jeffrey R.; Parrish, Damon; Shami, Paul J.; Findlay, Victoria J.; Townsend, Danyelle M.; Tew, Kenneth D.; Singh, Shivendra; Jia, Lee; Ji, Xinhua; Keefer, Larry K. Journal of Medicinal Chemistry, 2006 , vol. 49, # 3 p. 1157 - 1164

Full Text: HTML

Citation Number: 68

Abstract

PABA/NO is a diazeniumdiolate of structure Me2NN (O) NOAr (where Ar is a 5-substituted-2, 4-dinitrophenyl ring whose 5-substituent is N-methyl-p-aminobenzoic acid). It has shown activity against human ovarian cancer xenografts in mice rivaling that of cisplatin, but it is poorly soluble and relatively unstable in water. Here we report structure-based optimization efforts resulting in three analogues with improved solubility and stability in aqueous ...