تصميم أدوية مساعدة مبتكرة من حمض امينو كابروك بالطرق الحسابية
Date
2017-08-26
Authors
نداء مازن سالم لقيانية
neda mazen salem leqeanea
Journal Title
Journal ISSN
Volume Title
Publisher
AL-Quds University
جامعة القدس
جامعة القدس
Abstract
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)
Description
Keywords
العلوم الصيدلانية , Pharmaceutical Sciences