Abstract
Comparative DFT computations were studied between Paracetamol (PA) and its analogues such as p-nitroace- tanilide (PA-NO2), p-bromoacetanilide (PA-Br) and N-acetylanthranilic acid (NAA) which can be considered also as analogue of Aspirin (ASP). As well, Thio-Aspirin, Acetyl-Thio-Salicylic acid, (TASP) is another analogue of ASP. From DFT studies, it has been concluded that PA and its analogues have the predominant trans-conformers with respect to directions of the carbonyl group in the acetyl moiety and the amino-hydrogen atom but the predominant conformer of NAA molecule is the cis-form. Phenacetin (PH) molecule which has ethoxy group in the Para-position instead of the hydroxyl group in the Para-position in PA molecule is another analogue of PA. The electron transfer energy between the drugs and the nucleic acid bases can be illustrated as cancer energy barrier. The cancer energy barriers were calculated from the DFT parameters for all the studied molecules showing the carcinogenic effect. The metabolized product N-acetylimidoquinone, m-PA, is produced in the liver from PA and PH. m-PA has higher electron affinity more than those of the nucleic acid bases indicating to the strong electronic withdrawing power from the nucleus in the human being liver cell, hence m-PA is responsible for the carcinogenic behavior of the liver cell since it has low energy barrier with guanine, 0.3 eV. Therefore the electron transfer between m-PA and guanine takes place spontaneously in the liver. From CI calculations it has been concluded that the singlet transition energies for the trans and cis conformers of PA are the same. The comparative spectral studies have been scanned for some analogues in the visible and UV regions using solvents of different polarities. The complex between PA and Zn2+ was studied by DFT method.
Highlights
Paracetamol is worldwide used as analgesic and antipyretic drug [1] and there is a review by Vial et al [2] including 93 references discussing the clinical side effects of paracetamol in terms of the following system processes: allergic and skin; hematol; renal diseases; lactation of pregnant; carcinogenesis
The charge transfer complex formation between adenine, cytosine, thymine and uracil with catechol in acidic medium was studied by Al-Obeidi et al [9]
He proved that Aspirin and other non-steroid anti-inflammatory drugs (NSAIDs) inhibit the activity of the enzyme called cyclooxygenase (COX) which leads to the formation of prostaglandins (PGs) that cause inflammation, swelling, pain and fever
Summary
Paracetamol (acetaminophen) is worldwide used as analgesic and antipyretic drug [1] and there is a review by Vial et al [2] including 93 references discussing the clinical side effects of paracetamol in terms of the following system processes: allergic and skin; hematol; renal diseases; lactation of pregnant; carcinogenesis. Following the advent of synthetic salicylate, Felix Hoffman, working at the Bayer Company in Germany, made the acetylated form of salicylic acid in 1897. This drug was named “Aspirin” and became the most widely used medicine of all time. In 1971, Vane discovered the mechanism by which Aspirin exerts its anti-inflammatory, analgesic and antipyretic actions He proved that Aspirin and other non-steroid anti-inflammatory drugs (NSAIDs) inhibit the activity of the enzyme called cyclooxygenase (COX) which leads to the formation of prostaglandins (PGs) that cause inflammation, swelling, pain and fever. The constitutive iso-form, COX-1, supports the beneficial homeostatic functions, whereas the inducible iso-form, COX-2, becomes unregulated by inflammatory mediators and its products cause many of the symptoms of inflammatory diseases such as rheumatoid and osteoarthritis [13]
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