Available online at www.derpharmachemica.com Scholars Research Library Der Pharma Chemica, 2010, 2(6):197-210 (http://derpharmachemica.com/archive.html) ISSN 0975-413X 197 www.scholarsresearchlibrary.com Synthesis, Stability and Computational Study of some Ester Derivatives of Theophylline-7-acetic Acid with Antiproliferative Activity Alexander B. Zlatkov a * ) , Plamen T. Peikov a) , Georgi C. Momekov b) , Ivanka Pencheva a) , Boika Tsvetkova a) a) Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University - Sofia. b) Department of Pharmacology and Toxicology, Faculty of Pharmacy, Medical University – Sofia ______________________________________________________________________________ ABSTRACT Two new esters of theophylline-7-acetic acid were synthesized and their structures were confirmed by elemental analysis, FTIR, 1 H NMR spectral data. Structural analysis was also carried out using computational methods. The performed investigations on the spectral behaviour of the tested compounds show, that in comparison with the DFT calculations, the application of PM6 method is mainly limited to vibrations under 3000 cm -1 . From the performed stability evaluations was established that compounds 3a-b are stable in acidic and weakly alkaline pH. In strong alkiline solution 3a-b hydrolize and the corresponding rate constants were established. The analysis of the calculated molecular descriptors defined by Lipinski prove that the studied compounds obey “rule of five” and is very probable to expect good biological activity manifestation after peroral administration.The pharmacological screening in three human tumor cell lines show, that 3a causes reduction of cellular viability at lower concentration as compared to 3b. Key Words: antiproliferative activity, computational study, esters, stability, vibrational spectra. ______________________________________________________________________________ INTRODUCTION The purine system represents a versatile structural scaffold, whose extensive exploitation in drug design and discovery, has led to the identification of numerous lead compounds and subsequently commercialization of drugs with diverse biological effects including antineoplastic and immunosuppressive antimetabolites, adenosine receptor antagonists, xanthine oxydase and phosphodiesterase enzyme inhibitors etc. Among the purine-based drugs and lead compounds much attention has been paid to the structural modification of methylxanthines, due to their diverse pharmacological effects. Apart from the well established effects of methylxanthines on