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dc.contributor.authorKaraman, Rafik
dc.contributor.authorJumaa, Salma
dc.contributor.authorAwwadallah, Heba
dc.contributor.authorSalah, Samya
dc.contributor.authorKhawaja, Yahya
dc.contributor.authorKaraman, Donia
dc.date.accessioned2018-09-08T13:49:37Z
dc.date.available2018-09-08T13:49:37Z
dc.date.issued2015-11-15
dc.identifier.issn1385-2728
dc.identifier.urihttps://dspace.alquds.edu/handle/20.500.12213/860
dc.description.abstractThis review supplies the reader with a detailed overview on the utilization of intramolecular processes for a design and synthesis of prodrugs. It is well known that a respected number of drugs suffer from low bioavailability, toxicity, unpleasant taste and presystemic first-pass metabolism which result in drug inactivation. The classical prodrug approach in which the linkage attaching the parent drug to its non-toxic linker and cleaved by in vivo enzyme’s catalyzed reactions has proven its success in solving toxicity and bioavailability related issues. On the other hand, prodrugs based on chemical interconversion in which the prodrug releases the corresponding active parent drug via inter or intramolecular chemical process in the absence of an enzyme is considered as a better alternative approach since the prodrug cleavage is not dependent in the efficiency or quantity of the enzyme catalyzes the interconversion of the prodrug. Examples of successful prodrugs using the chemical approach via intramolecular processes such as cyclization reactions are illustrated as well. In addition, another part of this review is devoted to cover reported studies on enzyme models and their utilization for the design and synthesis of a variety of novel prodrugs. In this approach, computational calculations using DFT and MM methods were exploited and correlations between experimentally determined and computed values of the rate-limiting step in the studied intramolecular processes were utilized in the prodrugs design. Selected examples of the designed prodrugs include aza-nucleosides for the treatment of myelodysplastic syndromes, the anti-Parkinson’s agent dopamine, the anti-viral acyclovir, the anti-malarial atovaquone, and statins for lowering cholesterol levels in the blood, the antihypertensive atenolol, the antibacterial cefuroxime, the anti-bleeding tranexamic acid, the decongestant phenylephrine, and the pain killer paracetamol.en_US
dc.description.sponsorshipThe Karaman Co. is thanked for support of our computational facilities. Special thanks are also given to Angi Karaman, Natali Karaman, Sireena Karaman, Rowan Karaman and Nardene Karaman for technical assistance.en_US
dc.language.isoen_USen_US
dc.publisherBentham Scienceen_US
dc.subjectIntramolecularen_US
dc.subjectcyclizationen_US
dc.subjectprodrugen_US
dc.subjecttrimethyl locken_US
dc.subjectintramolecular Activationen_US
dc.subjectQuantum Mechanics Calculationsen_US
dc.subjectlactonization cyclizationen_US
dc.titleIntramolecular Processes and Their Applications in Prodrugs Approaches- Experimental and Computational Studiesen_US
dc.typeArticleen_US


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