Original article Investigation of the interaction between amodiaquine and human serum albumin by fluorescence spectroscopy and molecular modeling Fayezeh Samari a , Mojtaba Shamsipur b , Bahram Hemmateenejad a, * , Taghi Khayamian c , Sajjad Gharaghani c a Department of Chemistry, Shiraz University, Department of Chemistry, Adabiat Four-way, Shiraz, Fars 71454, Iran b Department of Chemistry, Razi University, Kermanshah, Iran c School of Chemistry, Isfahan University, of Technology, Isfahanm, Iran highlights graphical abstract < The interaction between amodia- quine and human serum albumin has been investigated. < The results obtained revealed that amodiaquine has moderate affinities for HAS and binds mainly to sub- domain IIA. < Hydrogen bonding formation and van der Waals forces play major role in the binding process. < The binding study was also modeled by molecular docking and molecular dynamic simulation. article info Article history: Received 9 March 2012 Received in revised form 28 April 2012 Accepted 3 May 2012 Available online 12 May 2012 Keywords: Human serum albumin Amodiaquin Fluorescence Binding Molecular modeling abstract The interaction of amodiaquine (AQ) with human serum albumin (HSA) has been studied by fluorescence spectroscopy. Based on the sign and magnitude of the enthalpy and entropy changes (DH 0 ¼43.27 kJ mol 1 and DS 0 ¼50.03 J mol 1 K 1 ), hydrogen bond and van der Waals forces were suggested as the main interacting forces. Moreover, the efficiency of energy transfer and distance between HSA and acceptor AQ was calculated. Finally, the binding of AQ to HSA was modeled by molecular docking and molecular dynamic simulation methods. Excellent agreement was found between the experimental and theoretical results. Both experimental results and modeling methods suggested that AQ binds mainly to the sub-domain IIA of HSA. Ó 2012 Elsevier Masson SAS. All rights reserved. 1. Introduction Malaria is still one of the major burdens of public health in sub- Saharan Africa. According to the last world health organization report, in the year 2010, 106 countries and areas are considered to be endemic for malaria with 750 million people at risk of contracting the disease; 225 million cases of malaria in 2009 was indicate that led to nearly a 781,000 deaths, mostly among African children under 5 years [1]. Amodiaquine (AQ, Fig. 1), for its chemical structure, is an estab- lished antimalarial drug recently reintroduced in the World Health Organisation Model List of Essential Medicines [2]. AQ is a 4- * Corresponding author. Tel.: þ98 711 613 7360; fax: þ98 711 228 6008. E-mail address: hemmatb@sums.ac.ir (B. Hemmateenejad). Contents lists available at SciVerse ScienceDirect European Journal of Medicinal Chemistry journal homepage: http://www.elsevier.com/locate/ejmech 0223-5234/$ e see front matter Ó 2012 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.ejmech.2012.05.007 European Journal of Medicinal Chemistry 54 (2012) 255e263