ЖɍɊɇАɅ ɋɌɊɍɄɌɍɊɇɈɃ ХɂɆɂɂ 2012. Ɍɨɦ 53, № 3 Маɣ – ɢюɧь ɋ. 580 – 587 UDC 541.6:548.737 THEORETICAL STUDY ON THE MOLECULAR ELECTRONIC PROPERTIES OF SALICYLIC ACID DERIVATIVES AS ANTI- INFLAMMATORY DRUGS E. Mousavinezhad Sarasia 1 , M.E.S. Soliman 2 , B. Honarparvar 3 1 Department of Biochemistry, Payame Noor University, Mashhad-IRAN 2 School of Pharmacy and Pharmacology, University of KwaZulu Natal, Durban 4001, South Africa 3 School of Chemistry, University of KwaZulu Natal, Durban, South Africa, e-mail: Honarparvar@ukzn.ac.za or bahareh_honarparvar@yahoo.com Received December, 14, 2010 A systematic computational study was carried out to determine the structural stability of sali- cylic acid derivatives as well as the acidic properties of the protonation-deprotonation site and excitation parameters of the considered drugs at different temperatures using quantum chemi- cal calculations. For further structural information, the dipole moment and differences in the energy of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecu- lar orbital (LUMO) as (HOMO—LUMO) were compared. A high stability of the salicylic ac- id derivatives was referred to the large HOMO—LUMO band gap. The result of the current study may give useful information about the drug biochemical functionality based on the phys- ical and chemical nature at different temperatures, and in this way the study on the structural features of analogous molecules of salicylic acid derivatives with higher drug functionality would be possible. K e y w o r d s: salicylamide (SAM), gentisamide (GAM), HOMO—LUMO band gap, excita- tion energies, ab initio. INTRODUCTION The investigation of the bioactivity of salicylic acid derivatives as the anti-inflammatory drugs depends on the ionization sites and the protonation-deprotonation mechanism of these drugs. Under- standing of the role of salicylic acid derivatives in biological processes is of great interest. Salicylamide (SAM) as a salicylic acid derivative is used with other analgesics or antipyretics. It is easily absorbed from the gastrointestinal tract and distributed to the body tissues. Although SAM is not as effective as acetilsalicylic acid or paracetamol, it is still used in Asia, North and South Ame- rica in combined medicines for symptoms associated with cold and influenza [ 1 ]. SAM and aceta- minophen mutually inhibit the formation of their corresponding sulfate and glucuronide conjugates. SAM is metabolized principally to an inactive glucuronide conjugate in adults and to an inactive sul- fate conjugate in children [ 2, 3 ]. SAM and paracetamol are extensively used antipyretic-analgesic drugs and are frequently prescribed in mixture with each other or with other related drugs. Therefore, their determinations in mixtures are required [ 4 ]. Several methods have been reported for the determination of salicylamide and paracetamol in mixtures. These include HPLC, spectrofluorimetric, electrochemical, and spectrophotometric methods [5—7 ]. Gentisamide (GAM) is the first-pass metabolite of SAM. SAM metabolizes rapidly to its primary metabolites, namely, SAM-sulfate (SAM-S), SAM-glucuronide (SAM-G), and gentisamide (GAM or SAM-OH), the 5-hydroxylated metabolite [ 8 ]. © MousКvТnОzСКН SКrКsТК E., Soliman M.E.S., Honarparvar B., 2012