title: Prodrugs design based on inter- and intramolecular chemical processes.
abstract: This review provides the reader a concise overview of the majority of prodrug approaches with the emphasis on the modern approaches to prodrug design. The chemical approach catalyzed by metabolic enzymes which is considered as widely used among all other approaches to minimize the undesirable drug physicochemical properties is discussed. Part of this review will shed light on the use of molecular orbital methods such as DFT, semiempirical and ab initio for the design of novel prodrugs. This novel prodrug approach implies prodrug design based on enzyme models that were utilized for mimicking enzyme catalysis. The computational approach exploited for the prodrug design involves molecular orbital and molecular mechanics (DFT, ab initio, and MM2) calculations and correlations between experimental and calculated values of intramolecular processes that were experimentally studied to assign the factors determining the reaction rates in certain processes for better understanding on how enzymes might exert their extraordinary catalysis.
authors.affiliation: Bioorganic Chemistry Department, Faculty of Pharmacy, Al-Quds University, P.O. Box 20002, Jerusalem, Palestine; Department of Science, University of Basilicata, Via dell'Ateneo Lucano 10, 85100, Potenza, Italy.
authors.forename: Rafik
authors.initials: R
authors.lastname: Karaman
mesh_terms: D001391:Azo Compounds / Q000737:chemistry / Q000378:metabolism; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D002384:Catalysis; D015195:Drug Design; D006207:Half-Life; D008958:Models, Molecular; D011092:Polyethylene Glycols / Q000737:chemistry; D011355:Prodrugs / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D001391:Azo Compounds; D001672:Biocompatible Materials; D011355:Prodrugs; D011092:Polyethylene Glycols
keywords: Ab initio calculations; DFT calculations; design of prodrugs; enzyme models; molecular mechanics calculations; prodrugs