Intramolecular Processes and Their Applications in Prodrugs Approaches- Experimental and Computational Studies Karaman, Rafik Jumaa, Salma Awwadallah, Heba Salah, Samya Khawaja, Yahya Karaman, Donia 2018-09-08T13:49:37Z 2018-09-08T13:49:37Z 2015-11-15
dc.description.abstract This 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.sponsorship The 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.identifier.issn 1385-2728
dc.language.iso en_US en_US
dc.publisher Bentham Science en_US
dc.subject Intramolecular en_US
dc.subject cyclization en_US
dc.subject prodrug en_US
dc.subject trimethyl lock en_US
dc.subject intramolecular Activation en_US
dc.subject Quantum Mechanics Calculations en_US
dc.subject lactonization cyclization en_US
dc.title Intramolecular Processes and Their Applications in Prodrugs Approaches- Experimental and Computational Studies en_US
dc.type Article en_US
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