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.

Objective: To assess the clinical characteristics and outcomes of cystic fibrosis in Palestine by studying the quality of life (QoL) of participants. Method: This cross-sectional study involved the application of Cystic Fibrosis Questionnaire-Revised (CFQ-R) to participants attending the pediatric pulmonology clinic at Caritas Baby Hospital between January and May 2017. Health status was assessed by measuring pulmonary function test (FEV 1 ), body mass index (BMI), age of CF diagnosis, and presence of other affected siblings or deaths in the family.Results: There were 77 participants from 58 families: 46.8% (36/77) were males, and 53.3% (41/77) were females. The mean age was 10.7 years (range: 0.5-36 years).The participants were divided into three groups by age in years: group I ( < 6), II (6-13), and III (≥ 14). The highest and lowest CFQ scores were for the eating domain in group III (55.6 ± 22.5) and the body domain in group II (14.5 ± 17.7), respectively.Mean illness severity was 69.6% (range: 33%-111%). The mean BMI was 15.9 (range: 9.6-23.1). The mean age at the time of diagnosis was 4.2 years (± 6.3). The study showed that 1.7% of the families (1/58) had four affected siblings, and 21% (12/58) had death cases related to CF, of which 58.3% (7/12) were from the Hebron district. Finally, all parameters for CF participants in West Bank, Palestine were noticeably lower than those reported in other countries.Conclusions: This study illustrates the need for new therapies for CF participants in Palestine to improve QoL, health status, and longevity.cystic fibrosis, quality of life | INTRODUCTIONCystic fibrosis (CF), also called mucoviscidosis, is a life-threatening inherited disease defined as a recessive genetic disease characterized by dehydration of the airway surface liquid and impaired mucociliary clearance. 1 The discovery of CF can be dated back to the Middle Ages, when people had the saying: "Woe to that child which when kissed on the forehead tastes salty. He is bewitched and soon must die." This is one of the earliest references to CF, recognizing the association between the salt loss in CF and illness, although the condition was unnamed at that time. 2 Although the number of CF patients is increasing around the world, there is no accurate epidemiological data on CF disease in Palestine. The general impression has been that the disease is rare, but this is most likely the result of under-diagnosis or misdiagnosis due to limited awareness of the condition in the region. This disease has a high treatment burden. Some of the novel technology used for drug delivery is highly beneficial because it may

Objective: To assess the quality of life (QoL) of Cystic fibrosis (CF) patients in West Bank, Palestine using the Cystic Fibrosis Questionnaire-Revised (CFQ-R) form. Method: A cross-sectional study involving application of CFQ-R questionnaire in CF patients attending pediatric pulmonology clinic at Caritas Baby Hospital (CBH). Their health status was assessed by measuring different parameters including pulmonary function test (FEV1) and body mass index (BMI). Results: The sample consisted of 77 patients from 58 families: 46.75% were males. Mean age was 10.7 years. Patients were divided into three groups by age in years: group I (< 6), II (6-13), and III (≥ 14). The highest and lowest CFQ scores were for the eat domain in group III (55.56 ± 22.49) and the body domain in group II (14.48 ± 17.67), respectively. Illness severity as measured by FEV1 mean value 69.6. BMI mean value of 15.998. The overall mean age at time of diagnosis in our sample was 4.16 years (± 6.239). The study showed that 1.7% of families had four affected siblings and 21% had death cases related to CF. Finally, all parameters for CF patients in West Bank, Palestine appear to be noticeably lower than those reported in other countries. Conclusions: quality of life for patients with CF is poor relative to international standards, the medications used including hypertonic saline and Gentamycin IV form used as nebulizer solution are not first line therapies around the world. This study illustrates the need of new therapies for CF patients in Palestine.