The use of residual dipolar couplings for conformational analysis of non-steroidal anti-inflammatory drugs dissolved in weakly ordering media

ABSTRACT

The three-dimensional structure and conformational equilibrium of flexible bioactive molecules in solution are of considerable importance in clarifying their role in chemical and biological activity, since their action takes place in a liquid medium. The use of residual dipolar couplings (RDCs) recently emerged as a promising and effective method to address this kind of investigation. In this brief review, the conformational analysis of several flexible non-steroidal anti-inflammatory drugs, belonging to the class of salicylates and α-arylpropionic acids (profens), is described using the RDCs measured in weakly aligning poly-γ-benzyl-l-glutamate solutions. By combining these experimental parameters, extracted by using different mono- and bi-dimensional nuclear magnetic resonance experiments, with the theoretical additive potential-direct probability description approach, accurate descriptions of the probability distributions have been obtained for all the drug molecules selected.

Graphical Abstract

KEYWORDS:

• Non-steroidal anti-inflammatory drugs
• NMR in weakly ordering media
• PBLG
• residual dipolar couplings
• conformational analysis

Acknowledgements

The present work has been supported by the “L’Oréal Italia per le Donne e la Scienza 2014” programme through the fellowship of M.E. Di Pietro. G. Celebre, G. De Luca, M.E. Di Pietro and R.A. Salvino thank University of Calabria for financial support.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The present work has been supported by the “L’Oréal Italia per le Donne e la Scienza 2014” programme through the fellowship of M.E. Di Pietro. G. Celebre, G. De Luca, M.E. Di Pietro and R.A. Salvino thank University of Calabria for financial support.