Pharmaceutical Sciences

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Browsing Pharmaceutical Sciences by Author ": Dr. Naser Shraim"

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    تصميم أدوية مساعدة مبتكرة من حمض امينو كابروك بالطرق الحسابية
    (AL-Quds University, 2017-08-26) نداء مازن سالم لقيانية; neda mazen salem leqeanea; رفيق قرمان; Dr. Hatem Hejaz; : Dr. Naser Shraim
    Background and objectives: Unraveling the mechanisms of a number of enzyme models has allowed for the design of efficient chemical devices having the potential to be utilized as prodrug linkers that can be covalently attached to commonly used drugs which can chemically, and not enzymatically, be converted to release the active drug in a programmable manner. For instance, exploring the mechanism for a proton transfer in Kirby‘s N-alkylmaleamic acids (enzyme model) has led to the design of a number of prodrugs such as tranexamic acid, acyclovir, atenolol. Method: Based on density functional theory (DFT) calculations for the acid-catalyzed hydrolysis of several N-alkylmaleamic acid derivatives five 6-aminocapproic acid prodrugs were designed, aiming to provide a drug with potentially to have higher bioavailability than its parent drug. Result and discussion: DFT calculations at B3LYP/6-31G(d,p) for intramolecular proton transfer in 1-7 and prodrugs of 6-aminocapproic acid, ProD1-ProD5, demonstrated that the reaction rate is dependent on the strain energy difference between the intermediate and the reactant (Es INT-GM). This suggests that the reaction is governed by strain effect. Additionally, no correlation was found between the proton transfer efficiency and the distance between the two reactive centers (rGM) and the attack angle (α). Conclusion: Hence, the rate by which the prodrug releases the 6-aminocapproic acid drug can be determined according to the structural features of the promoiety (Kirby’s enzyme model)