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Peptide chemistry applied to a new family of phenothiazine-containing inhibitors of human farnesyltransferase
Affiliation:1. Department of Organic Chemistry, Faculty of Chemistry, ‘Al. I. Cuza’ University of Iasi, B-dul Carol I, Nr. 11, Corp A, 700506 Iasi, Romania;2. Univ Lille Nord de France, F-59000 Lille, France;3. UCLille, EA GRIIOT (4481), Laboratoire de pharmacochimie, HEI, 13 rue de Toul, F-59046 Lille, France;4. Institut de Chimie des Substances Naturelles, UPR2301 CNRS, Centre de Recherche de Gif, Avenue de la Terrasse, F-91198 Gif-sur-Yvette Cedex, France;5. Institut de Chimie Pharmaceutique Albert Lespagnol, EA GRIIOT (4481), IFR114, 3 Rue du Pr Laguesse, B.P. 83, F-59006 Lille, France;1. Center for Pharmacy and Department of Chemistry, University of Bergen, Bergen N-5007, Norway;2. School of Pharmacy, University of Oslo, Oslo N-0376, Norway;1. Centre for Nanobiotechnology, VIT University, Vellore 632014, Tamil Nadu, India;2. School of Advanced Sciences, VIT University, Vellore 632014, Tamil Nadu, India;1. Department of Cardiothoracic Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China;2. College of Bioengineering, Chongqing University, Chongqing 400044, China;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo, 11829, Egypt;2. Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy;3. Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy;4. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, P.O. Box 11566, Abbassia, Cairo, Egypt;5. Department of Applied Organic Chemistry, National Research Center, Dokki, Cairo, 12622, Egypt;1. Pediatric Hematology/Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo, Pavia, Italy;2. Cell Factory, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo, Pavia, Italy;3. Section of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Azienda Ospedaliera Universitaria (AOU) Policlinico, Modena, Italy;4. Section of Hematology, University of Ferrara, Ferrara, Italy;5. Section of Pediatric Hemato-Oncology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Policlinico, Modena, Italy;6. Department of Laboratory Medicine and Pathology, Unità Sociosanitaria Locale, Modena, Italy;7. Hematology, Department of Cellular Biotechnologies and Hematology, Policlinico Umberto 1, Sapienza University, Rome, Italy
Abstract:Novel phenothiazine derivatives bearing an amino acid residue were synthesized via peptide chemistry, and evaluated for their inhibitory potential on human farnesyltransferase. The phenothiazine unit proved to be an important bulky unit in the structure of the synthesized inhibitors. Propargyl ester 20 bearing a tyrosine residue exhibited the best biological potential in vitro in the present study. Further syntheses and biological evaluation of phenothiazine derivatives are necessary in order to gain a full view of SAR in this family of farnesyltransferase inhibitors.
Keywords:Farnesyltransferase inhibitor  Phenothiazine  Peptide coupling  Activated ester
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