title: 1H NMR spectroscopic identification of protonable sites in cryptolepines with C-11 substituents containing two amino functionalities.
abstract: Knowledge of protonable sites and acid dissociation constants of cryptolepine derivatives having C-11 substituents containing two amino functionalities is of great importance to the understanding of the mechanism of their antimalarial action, which may contribute to their further development as drug candidates. In this work, we applied (1)H NMR titration to investigate the acid-base characteristics of these polyprotic compounds in the pH range 3-13. We identified three acid-base equilibria with most acid dissociation constants (pK(a)*) being greater than 10.5, which prevented us from using the potentiometric method. Overall, (1)H NMR titration was sensitive and suitable for the determination of pK(a) values for these drug leads.
authors.affiliation: iMed-UL, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Lavrado
authors.forename: Alexandra
authors.initials: A
authors.lastname: Paulo
authors.forename: Elena
authors.initials: E
authors.lastname: Bichenkova
authors.forename: Kenneth T
authors.initials: KT
authors.lastname: Douglas
authors.forename: Rui
authors.initials: R
authors.lastname: Moreira
mesh_terms: D000136:Acid-Base Equilibrium; D000962:Antimalarials / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D026121:Indole Alkaloids / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000592:standards; D015394:Molecular Structure; D011522:Protons; D011804:Quinolines / Q000737:chemistry*; D012015:Reference Standards
chemical_list: D000962:Antimalarials; D026121:Indole Alkaloids; D011522:Protons; D011804:Quinolines; C024015:cryptolepine