Nuclear magnetic resonance and molecular modeling analysis of the interaction of the antimalarial drugs artelinic acid and artesunic acid with beta-cyclodextrin

Journal of Pharmaceutical Sciences
Mark G HartellJohn E Van Hamont

Abstract

The artemisinin derivatives artelinic acid and artesunic acid are members of a class of compounds that have shown promise for the treatment of multidrug resistant strains of Plasmodium falciparum. Unfortunately, these compounds exhibit poor solubility and stability in aqueous solution. The research presented herein was conducted to determine whether complexation of artelinic acid or artesunic acid with beta-cyclodextrin would result in complexes with increased aqueous solubility while retaining the potent antimalarial activity of these compounds. Preliminary complexation studies with natural beta-cyclodextrins were conducted as a proof of concept, with a primary focus on understanding the electrostatic interactions that stabilize the resulting complexes. Complex formation was monitored using UV spectroscopy. The structures of the resulting complexes were determined using multidimensional nuclear magnetic resonance spectroscopy (NMR) and molecular modeling. NMR results are most consistent for artelinic acid and beta-cyclodextrin forming complexes in a ratio of 2:1; however, the presence of 1:1, 2:2, and 3:1 complexes in solution cannot be excluded based on the experimental data collected. The NMR data also indicate selective ins...Continue Reading

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Citations

Jul 25, 2006·Transactions of the Royal Society of Tropical Medicine and Hygiene·Qigui LiPeter J Weina
Nov 7, 2013·Advances in Colloid and Interface Science·N P AdityaE B Souto
Feb 22, 2012·Drug Development and Industrial Pharmacy·Renu ChadhaNatasha Pathak
Jul 31, 2016·Carbohydrate Polymers·Pollyana S S LimaJullyana S S Quintans
Nov 17, 2009·Advanced Drug Delivery Reviews·Nereide Stela Santos-Magalhães, Vanessa Carla Furtado Mosqueira

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Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.