Abeer M Al-Ghananeem † and Peter A Crooks*
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington,
Kentucky 40536, USA; † e-mail: amalg0@email.uky.edu
* Author to whom correspondence should be addressed; E-mail: pcrooks@email.uky.edu
Received: 10 February 2007; in revised form: 5 March 2007 / Accepted: 5 March 2007 / Published: 8 March 2007
Review: Phase I and Phase II Ocular Metabolic Activities and the Role of Metabolism in Ophthalmic Prodrug and Codrug Design and Delivery
Molecules 2007, 12, 373-388 (PDF format 80 K)
Elina Sievänen
University of Jyväskylä, Department of Chemistry, P.O. Box 35, FIN-40014 University of Jyväskylä, Finland; E-mail: elvirtan@cc.jyu.fi
Received: 6 June 2007; in revised form: 13 August 2007 / Accepted: 14 August 2007 / Published: 16 August 2007
Review: Exploitation of Bile Acid Transport Systems in Prodrug Design
Molecules 2007, 12, 1859-1889 (PDF format 159 K)
(This paper also belongs to Special Issue on Bile acids,edited by Dr. Erkki Kolehmainen)
Paula Gomes 1,*, Nuno Vale 1 and Rui Moreira 2
1 Centro de Investigação em Química da Universidade do Porto, Departamento de Química, Faculdade de Ciências, Universidade do Porto, Porto, Portugal
2 Centro de Estudos de Ciências Farmacêuticas, Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal
* Corresponding author: R. Campo Alegre 687, P-4169-007 Porto, Portugal; Phone: + 351220402563; Fax: +351 220402659; E-mail: pgomes@fc.up.pt
Received: 6 October 2007; in revised form: 8 November 2007 / Accepted: 9 November 2007 / Published: 12 November 2007
Review: Cyclization-activated Prodrugs
Molecules 2007, 12, 2484-2506 (PDF format 158 K)
Yoshifumi Murata 1,*, Daisaku Jinno 1, Dongchun Liu 2, Takshi Isobe 1, Kyouko Kofuji 1 and Susumu Kawashima 1
1 Faculty of Pharmaceutical Science, Hokuriku University, Ho-3, Kanagawa-machi, Kanazawa 920-1181, Japan
2 Department of Pharmacognosy, Shenyang Pharmaceutical University, Wen Hua Road 103, mailbox 48, Shenhe, Shenyang, 110016, PRC
* Author to whom correspondence should be addressed; E-mail: y-murata@hokuriku-u.ac.jp; Phone: +81-076-229-6184; Fax: +81-076-229-2781
Received: 17 November 2007; in revised form: 27 November / Accepted: 27 November 2007 / Published: 29 November 2007
Full Paper: The Drug Release Profile from Calcium-induced Alginate Gel Beads Coated with an Alginate Hydrolysate
Molecules 2007, 12, 2559-2566 (PDF format 109 K)
Antonio Di Stefano*, Piera Sozio and Laura Serafina Cerasa
Department of Drug Sciences, “G. d'Annunzio” University, School of Pharmacy, Via dei Vestini 31, 66100 Chieti, Italy
* Author to whom correspondence should be addressed. Tel.: +39-871-3554708; fax: +39-871-3554706; E-mail: adistefano@unich.it
Received: 4 December 2007; in revised form: 11 January 2008 / Accepted: 11 January 2008 / Published: 16 January 2008
Review: Antiparkinson Prodrugs
Molecules 2008, 13, 46-68 (PDF format 172 K)
Andrea Brioschi 1,*, Gian Paolo Zara 2, Sara Calderoni 3, Maria Rosa Gasco 4 and Alessandro Mauro 1,5
1 Istituto Auxologico Italiano, IRCCS – Department of Neurology – Ospedale S. Giuseppe, Piancavallo, PO. Box 1 – 28921 Verbania, Italy
2 University of Torino – Department Anatomy Pharmacology Forensic Medicine – Torino, Italy
3 Istituto Auxologico Italiano, IRCCS – Department of Neurology – Laboratory of Clinical Neurobiology – Verbania, Italy
4 Nanovector S.r.l. – Torino, Italy
5 University of Torino – Departement of Neurosciences – Torino, Italy
* Author to whom correspondence should be addressed; E-mail: a.brioschi@auxologico.it
Received: 4 January 2008; in revised form: 31 January 2008 / Accepted: 1 February 2008 / Published: 1 February 2008
Review: Cholesterylbutyrate Solid Lipid Nanoparticles as a Butyric Acid Prodrug
Molecules 2008, 13, 230-254 (PDF format 148 K)
Francesca Leonelli, Angela La Bella, Luisa Maria Migneco and Rinaldo Marini Bettolo*
Dipartimento di Chimica and Istituto di Chimica Biomolecolare del CNR, Sezione di Roma, Università degli Studi di Roma "La Sapienza”, P.le Aldo Moro 5, BOX n. 34 ROMA 62, I-00185 Roma, Italy; E-mails: francesca.leonelli@uniroma1.it, angela.labella@uniroma1.it, luisamaria.migneco@uniroma1.it
†Dedicated to the Memory of Prof. Vittorio Crescenzi [1]
* Author to whom correspondence should be addressed. E-mail: rinaldo.marinibettolo@uniroma1.it
Received: 29 January 2008; in revised form: 11 February 2008 / Accepted: 11 February 2008 / Published: 12 February 2008
Review: Design, Synthesis and Applications of Hyaluronic Acid-Paclitaxel Bioconjugates†
Molecules 2008, 13, 360-378 (PDF format 106 K)
Amin I. Kassis*, Houari Korideck, Ketai Wang, Pavel Pospisil and S. James Adelstein
Department of Radiology, Harvard Medical School, Armenise Building, Room D2-137, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
*Author to whom correspondence should be addressed. Telephone: (617) 432-7777; Fax: (617) 432-2419; E-mail: amin_kassis@hms.harvard.edu
Received: 6 February 2008 / Revised version received: 15 February 2008 / Accepted: 15 February 2008 / 18 February 2008
Review: Novel Prodrugs for Targeting Diagnostic and Therapeutic Radionuclides to Solid Tumors
Molecules 2008, 13, 391-404 (PDF format 632 K)
Helieh S. Oz* and Jeffrey L. Ebersole
Center for Oral Health Research, College of Dentistry and Department of Internal Medicine, University of Kentucky, Medical Center, 800 Rose Street, Lexington, KY 40536, USA; E-mail: jleber2@uky.edu (Jeffrey L. Ebersole)
* Author to whom correspondence should be addressed; E-mails: helieh.oz@uky.edu; hsoz1@hotmail.com; Phone: +1 (859) 323-0887
Received: 26 January 2008; in revised form: 20 February 2008 / Accepted: 21 February 2008 / Published: 27 February 2008
Review: Application of Prodrugs to Inflammatory Diseases of the Gut
Molecules 2008, 13, 452-474 (PDF format 142 K)
Corrigendum: Correction to Oz, H.S.; Ebersole, Jeffrey L. Application of Prodrugs to Inflammatory Diseases of the Gut. Molecules 2008, 13, 452-474
Received: 31 March 2008 / Accepted: 1 April 2008 / Published: 1 April 2008
Molecules 2008, 13, 771 (PDF format 18 K)
Ana L. Simplício 1,2,*, John M. Clancy 3 and John F. Gilmer 3
1 Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Av. da República – EAN, 2780-157 Oeiras, Portugal
2 IBET, Apartado 12, 2781-901 Oeiras, Portugal
3 School of Pharmacy, Trinity College, Dublin 2, Ireland; E-mails: jclancy@tcd.ie; gilmerjf@tcd.ie
* Author to whom correspondence should be addressed; E-mail: anas@itqb.unl.pt
Received: 14 December 2007; in revised form: 25 February 2008 / Accepted: 25 February 2008 / Published: 3 March 2008
Review: Prodrugs for Amines
Molecules 2008, 13, 519-547 (PDF format 165 K)
ID: prodrugs-20061218-Onishi-jp
Title: Recent Drug Delivery Systems to Utilize Macromolecular Prodrugs
Authors: Hiraku Onishi * and Yoshiharu Machida
Department of Drug Delivery Research, Hoshi University, 2-4-41, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
* E-mail: onishi@hoshi.ac.jp
Abstract: To be added
Molecules Manuscript ID: prodrugs-20070223-Tabrizian-ca
Title: Prodrugs in Cardiovascular Therapy
Marinella G. Sandros and Maryam Tabrizian
*corresponding author: maryam.tabrizian@mcgill.ca
Abstract: Advancement in the field of interventional cardiology has lead to the development of drug eluting stents (DES). DES are devices implanted in patients with coronary artery disease, which release therapeutic drugs to inhibit restenosis. One of the major challenges with DES is developing effective therapeutic delivery systems capable of providing sustained and controlled release of bioactive “agents” or “drugs”. Prodrugs are biologically inactive derivative of an active drug intended to permeate certain barriers in the parent drug such as toxicity, instability, minimal solubility and non-targeting capabilities. Since prodrugs undergo a chemical reaction to form the parent drug once inside the body, this makes them very effective in controlling the release of a variety of compounds to targeted site. This review will provide the reader with an insight on the various designs and applications of prodrugs with coronary revascularization procedures with a special emphasis on their integration into DES devices.
Molecules Manuscript ID: prodrugs-20071026-Chung-br
Title: Prodrugs for the Treatment of Neglected Diseases
Chung, M.C.1, Ferreira, E.I2, Santos, J.l2, Giarolla, J2, Rando, D.G2, Almeida, A.E.1, Bosquesi, P. L.1, Santos, J.L1, Menegon, R.F.1, Blau, L.1
1 Lapdesf. Laboratory of Prodrug Design. Department of Drugs and Medicine. School of Pharmaceutical Sciences – University of Sao Paulo State (UNESP) – Araraquara –SP- Brazil.
2. Department of Pharmacy. School of Pharmaceutical Sciences – University of Sao Paulo (USP) – Sao Paulo – Brazil
Abstract: Recently, WHO (World Health Organization) and MSF (Medicins San Frontieres) proposed the classification of the diseases in: global, neglected and extremely neglected. Global disease as cancer, cardiovascular and mental (CNS) diseases represent the most of R&D efforts of Pharmaceutical Companies. Neglected diseases affect thousands of people in the world with lack of effectiveness or appropriate treatments. Besides, extremely neglected diseases affect people that are miserable that practically do not have any conditions of purchase. Most of those diseases are excluded of the goal of R&D in the Pharmaceutical Industry and, therefore, are out of the pharmaceutical market. About 14 million people die each year of infection diseases, mainly in developing countries. From 1975 to 1999, 1393 new drugs were approved and only 1% was to treat neglected diseases. This data have not changed until now. So, the design and synthesis of new drugs are urgently necessary for those countries and the prodrugs approach is a very interesting field. It provides the improvement activity and decrease toxicity of current and new drugs towards market availability. Its worth noting that to save time and funds is essential and prodrug design accomplishes these goals. The present review comprehends 20 years on prodrug design researches for the treatment of neglected and extremely neglected diseases: Chagas´disease (American trypanosomisasis), Sleeping sickness (African trypanosomiasis), malaria, sickle cell disease, tuberculosis, leishmaniasis and schistosomiasis.
Type of the paper: Review
Title: Progress in Topics for Drugs Delivery to the Central Nervous System
Authors: Barbara Pavan*, Alessandro Dalpiaz, Nunzia Ciliberti, Carla Biondi, Stefano Manfredini and Silvia Vertuani
E-mail: pvnbbr@unife.it
Abstract: This review describes important strategies for drugs targeting to the central nervous system (CNS). Systemically administered drugs can reach the brain by crossing one of two physiological barriers resistant to free diffusion of most molecules from blood to CNS: the endothelial blood-brain barrier or the epithelial blood-cerebrospinal fluid barrier. These tissues constitute both transport and enzymatic barriers. The most common strategy in designing effective prodrugs rely in the increase of parent drug lipophilicity. However, increasing lipophilicity without concomitant increase in rate and selectivity of prodrug bioconversion in the brain will result in failure. In these regards, consideration of the enzymes present in brain tissue and in the barriers is essential for a successful approach. The nasal administration of lipophilic prodrugs can overcome these problems, allowing selective brain targeting of the parent drugs. The carrier-mediated absorption of drugs and prodrugs across epithelial and endothelial barriers is emerging as another novel trend in biotherapeutics. Several specific transporters have been identified in boundary tissues between blood and CNS compartments. Some of them are involved in the active supply of nutrients and have been used to explore prodrug approaches with improved brain delivery. The feasibility of CNS uptake of appropriately designed prodrugs via these transporters is described in detail.
Molecules Manuscript ID: prodrugs-20071204-Montenegro-it
Type of the paper: Review
Tentative Title: The prodrug approach: a strategy to improve drug skin permeation
Authors: L. Montenegro *, C. Carbone, G. Puglisi
Department of Pharmaceutical Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy
E-mail: lmontene@unict.it
Abstract: The skin is regarded as a valuable portal for drug delivery. However, drug skin permeation is strongly limited by the formidable barrier function of the skin and by the unsuitable physicochemical properties of most drugs. Therefore many strategies have been proposed to improve drug skin permeability such as the prodrug approach. The prodrug concept involves the chemical modification of a drug into a bioreversible form in order to change its pharmaceutical and pharmacokinetic properties and thereby enhancing its skin permeation and therapeutic efficacy. In this review prodrugs which have been investigated to improve topical and transdermal drug delivery are considered along with their potential applications in the pharmaceutical field.
Molecules Manuscript ID: prodrugs-20071205-Jasti-us
Type of the paper: Review
Tentative Title: Prodrugs: A review and Evolving Strategies
Authors: Saroj Vangani, Xiaoling Li, and Bhaskara R. Jasti*
Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long
School of Pharmacy and Health Sciences, University of the Pacific,
Stockton, CA 95211, USA
E-mail: bjasti@pacific.edu
Abstract: Prodrugs are agents that have no inherent pharmacological activity per se, but get converted to its parent molecule and elicit pharmacological action. Prodrug design has helped to manipulate physcochemical, biopharmaceutical or pharmacokinetic properties of drugs and resolved many challenges associated with solubility and permeability, targeting, stability and presystemic metabolism. The most preferred approach for prodrug design has been the chemical approach through derivatization. This review highlights examples of prodrugs that achieved commercial success from each of the therapeutic classes and different evolving strategies in prodrug design.
Molecules Manuscript ID: prodrugs-20071221-Rusnati-it
Type of the paper: Review
Tentative Title: Polysulfated/Polysulfonated Compounds for the Development of Drugs at the Crossroad of Tumor and Infectious Dideases
Authors: Chiara Urbinati, Paola Chiodelli, Marco Presta and Marco Rusnati
Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, Italy
E-mail: rusnati@med.unibs.it
Abstract: Polyanionic compounds are an heterogeneous group of synthetic, semisynthetic or natural molecules whose prototypes are polysulfated heparin and polysulfonated suramin. Polyanionic compounds can structurally vary for backbone structure and length and for number and disposition of sulfated/sulfonated groups. Different combinations of all these features confer to polyanionic compounds the capacity to bind with a variable degree of specificity and affinity many proteins such as enzymes, proteases, extracellular matrix components, cytokines, chemokines, growth factors and their receptors. Also, polyanionic compounds bind different components of pathogenic microorganisms, mainly viruses. Polyanionic compounds mirror the binding capacities of cell- or extracellular matrix-associated heparan sulfate proteoglycans, that act indeed as receptors for many of the proteins cited above. On these bases, polyanionic compounds have been taken in considerations as inhibitors of different pathological processes, in particular tumor growth, metastatization and angiogenesis, infection, virus replication, leukocyte recruitment and inflammation. Being some of these processes overlapping, polyanionic compounds may act as multitarget drugs, thus able to control a given disease by blocking different pathological processes simultaneously. Here we discuss this possibility in light of the available literature data.
Francesco Puoci 1,*, Francesca Iemma 1, Giuseppe Cirillo 1, Nevio Picci 1, Pietro Matricardi 2 and Franco Alhaique 2
1 Dipartimento di Scienze Farmaceutiche, Università della Calabria, Edificio Polifunzionale, Arcavacata di Rende (CS) 87036, Italy
2 Dipartimento di Studi di Chimica e Tecnologia delle Sostanze Biologicamente Attive, University “La Sapienza”, P.le A. Moro 5, 00185 Roma, Italy
* Author to whom correspondence should be addressed; email: francesco.puoci@unical.it; Tel. (+39) 0984493151, fax (+39) 0984493151
Received: 21 March 2007; in revised form: 13 March 2007 / Accepted: 16 April 2007 / Published: 18 April 2007
Full Paper: Molecularly Imprinted Polymers for 5-Fluorouracil Release in Biological Fluids
Molecules 2007, 12, 805-814 (PDF format 69 K)
Jesper Østergaard* and Claus Larsen†
Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen O, Denmark; †E-mail: csl@farma.ku.dk
* Author to whom correspondence should be addressed. E-mail: joe@farma.ku.dk
Received: 28 September 2007; in revised form: 29 October 2007 / Accepted: 29 October 2007 / Published: 30 October 2007
Full Paper: Bioreversible Derivatives of Phenol. 1. The Role of Human Serum Albumin as Related to the Stability and Binding Properties of Carbonate Esters with Fatty Acid-like Structures in Aqueous Solution and Biological Media
Molecules 2007, 12, 2380-2395 (PDF format 107 K)
Jesper Østergaard* and Claus Larsen†
Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen O, Denmark; †E-mail: csl@farma.ku.dk
* Author to whom correspondence should be addressed. E-mail: joe@farma.ku.dk
Received: 28 September 2007; in revised form: 29 October 2007 / Accepted: 29 October 2007 / Published: 30 October 2007
Full Paper: Bioreversible Derivatives of Phenol. 2. Reactivity of Carbonate Esters with Fatty Acid-like Structures Towards Hydrolysis in Aqueous Solutions
Molecules 2007, 12, 2396-2412 (PDF format 156 K)
Ebru Mete 1, Halise Inci Gul 2,* and Cavit Kazaz 1
1 Department of Chemistry, Faculty of Arts and Sciences, Ataturk University, 25240, Erzurum, Turkey
2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University, 25240, Erzurum, Turkey
* Author to whom correspondence should be addressed; E-mail: incigul1967@yahoo.com or incigul@atauni.edu.tr; Tel: +90-442-2311539; Fax: +90-442-2360962
Received: 29 October 2007; in revised form: 26 November 2007 / Accepted: 10 December 2007 / Published: 12 December 2007
Full Paper: Synthesis of 1-Aryl-3-phenethylamino-1-propanone Hydrochlorides as Possible Potent Cytotoxic Agents
Molecules 2007, 12, 2579-2588 (PDF format 80 K)
Nelly Alejandra Espinoza-González 1, Oliverio Welsh 1, Noemi Waksman de Torres 2, Norma Cavazos-Rocha 2, Jorge Ocampo-Candiani 1, Salvador Said-Fernandez 3, Gerardo Lozano-Garza 3, Sung-Hak Choi 4 and Lucio Vera-Cabrera 1,*
1 Servicio de Dermatología, Hospital Universitario “Dr. José E. González” Ave. Madero y Gonzalitos S/N Col. Mitras Centro Monterrey, N.L. México 64460; E-mail: nelly.espinoza@gmail.com
2 Departamento de Química Analítica, Facultad de Medicina, Universidad Autónoma de Nuevo León,
Ave. Madero y Dr. Eduardo Aguirre Pequeño S/N, Col Mitras Centro, Monterrey, N.L., México 64460
3 Centro de Investigación Biomédica del Noreste (CIBIN) del IMSS, 2 de Abril y San Luis Potosí, Col. Independencia, Monterrey, N.L., México 64720
4 Research Laboratory, Dong-A Pharmaceutical Co., Ltd., Yongin, and College of Pharmacy, Sungkyunkwan University, Suwon, South Korea
* Author to whom correspondence should be addressed: E-mail: luvera_99@yahoo.com
Received: 2 November 2007; in revised form: 29 December 2007 / Accepted: 29 December 2007 / Published: 11 January 2008
Full Paper: Efficacy of DA-7218, a New Oxazolidinone Prodrug, in the Treatment of Experimental Actinomycetoma Produced by Nocardia brasiliensis
Molecules 2008, 13, 31-40 (PDF format 215 K)
Marcin Sobczak*, Ewa Witkowska, Ewa Olędzka and Waclaw Kolodziejski
Medical University of Warsaw, Faculty of Pharmacy, Department of Inorganic and Analytical Chemistry, ul. Banacha 1, 02-097 Warsaw, Poland; E-mails: dr.witt@wp.pl (E. Witkowska),
eoledzka@wp.pl (E. Olędzka), waclaw@farm.amwaw.edu.pl (W. Kolodziejski)
* Author to whom correspondence should be addressed; E-mail: marcin.sobczak@wp.pl; Tel.: +48 22 572 07 55; Fax: +48 22 572 07 84.
Received: 14 December 2007; in revised form: 16 January 2008 / Accepted: 16 January 2008 / Published: 18 January 2008
Full Paper: Synthesis and Structural Analysis of Polyester Prodrugs of Norfloxacin
Molecules 2008, 13, 96-106 (PDF format 94 K)
Michael N. Levine 1, Luke D. Lavis 2 and Ronald T. Raines 1,2,*
1 Department of Biochemistry, University of Wisconsin–Madison, 433 Babcock Drive, Madison, WI 53706-1544, USA
2 Department of Chemistry, University of Wisconsin–Madison, 1101 University Avenue, Madison, WI 53706-1322, USA
* Author to whom correspondence should be addressed; E-mail: rtraines@wisc.edu
Received: 19 January 2008 / Accepted: 30 January 2008 / Published: 31 January 2008
Full Paper: Trimethyl Lock: A Stable Chromogenic Substrate for Esterases
Molecules 2008, 13, 204-211 (PDF format 140 K)
Karl Vollmann, Ramatullah Qurishi, Jörg Hockemeyer and Christa E. Müller*
Pharma-Center Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, An der Immenburg 4, D-53121 Bonn, Germany; http://www.pharmazentrum.uni-bonn.de/ and http://www.pharma.uni-bonn.de/pharmchem/
* Author to whom correspondence should be addressed; E-mail: christa.mueller@uni-bonn.de
Received: 29 January 2008; in revised form: 11 February 2008 / Accepted: 11 February 2008 / Published: 12 February 2008
Full Paper: Synthesis and Properties of a New Water-Soluble Prodrug of the Adenosine A2A Receptor Antagonist MSX-2
Molecules 2008, 13, 348-359 (PDF format 96 K)
Manuscript ID: prodrugs-20080204-Prokai-us
Type of the paper: Full Paper
Tentative title: TRH prodrugs as CNS agents
Author: Katalin Prokai-Tatrai, Ph. D.
Res. Assoc. Professor
Pharmacology & Neuroscience
University of North Texas Health Science Center at Fort Worth
3500 Camp Bowie Blvd.
Fort Worth, Texas 76107-2699
phone: (817) 735 0617
email: kprokai@hsc.unt.edu