Antibiotics Volume III

Mechanism of Action of Antimicrobial

and Antitumor Agents

Edited by

John W. Corcoran and Fred E. Hahn Assisted by J. F. Snell and K. L. Arora

Springer-Verlag Berlin· Heidelberg· New York 1975

Professor JOHN W. CORCORAN, Ph.D., Northwestern University, Department of Biochemistry, The Medical and Dental Schools, 303 E. Chicago Avenue, Chicago,

Illinois 60611jUSA

Professor FRED E. HAHN, Ph.D., Department of the Army, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington, D. C.

20012jUSA

ISBN-13: 978-3-642-46306-8 DOl: lO.lO071 978-3-642-46304-4

e-ISBN-13: 978-3-642-46304-4

This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically those of translation, reprinting, re-use of illustrations, broadcasting, reproduction by photocopying machine or similar means, and storage in data banks. Under § 54 of the German Copyright Law, where copies are made for other than private use, a fee is payable to the publisher, the amount of the fee to be determined by agreement with the publisher. © by Springer-Verlag Berlin

Heidelberg 1975. Library of Congress Catalog Card Number 74-34. Softcover reprint of the hardcover 1st edition 1975

The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations

and therefore free for general use.

Typesetting, printing and bookbinding: Stiirtz AG, Wiirzburg

Preface

This volume is the third in the series devoted to Antibiotics initiated by Springer Verlag in 1967. The first two volumes were devoted to the Mode of Action of Antibiotics and Biogenesis, respectively and were received graciously. During the intervening years these two works have been used often by research workers and students alike and have been quoted extensively. Although a number of other excellent treatises on antibiotics have appeared, the Springer series has set a standard for thoroughness and quality that meets the need of the scientific community.

It is against this background that the present Editors set about the preparation of a third volume in the Series on Antibiotics. Since the appearance of Volume I, also dealing with Mechanism of Action, tremendous strides have been made in the depth and breadth of our knowledge of molecular biology, microbial chemistry and molecular pharmacology and of their direct application to studies on the mode of action of drugs. The field of molecular biology itself was in its relative infancy during the preceding decade and the unique role played by many anti­biotics in the development of our understanding of nucleic acid synthesis and function and its relationship to protein synthesis and cell physiology has led rapidly to a very precise, understanding of how many of these same antibiotics inhibit susceptible cells. Thus, a,:, few years since the preparation of Volume I we feel that a new volume on antibiotic action may be offered which is almost com­pletely new in its content and which may prove useful to student, teacher and research worker alike.

A definition of classification of antimicrobial agents in terms of their origin is now largely academic. Accordingly, the selection of topics was based on the state of our knowledge of mechanisms of action. With few exceptions authors could be found to write on the major antimicrobial agents meeting this criterion and all elected are primary authorities on their subject. The Editors' efforts were aimed at assembling a volume whose various chapters have been prepared within one year of submission to the publisher and with a very few exceptions this goal has been achieved. When the first version of a chapter was written much earlier than desired, the authors have been encouraged to make any necessary revisions and most have done this. The result offered now is a treatise containing forty-six separate chapters dealing with both natural and synthetic antimicrobial agents (here again the distinction is somewhat academic, for at least half a dozen sub­stances are of both natural and synthetic origin). The chapters are well supported by citations of the original source literature (over 3500) and subject distribution reflects today's trend toward increased research on anti-tumor agents. Some thirty-three percent of the chapters deal with this subject. In addition, a broad spectrum of information is presented in this volume on the mode of action of certain well-known antimalarial, antitubercular and antiparasitic compounds.

IV Preface

Of the forty-six topics presented, twenty-eight are new to the Springer series on Antibiotics. Others are dealt with again because there has been a significant advance in our understanding of their mode of action since the initial treatment.

The editors have attempted only a general organization of the subjects included in the present Volume. Then guidelines have been suggested by the limited number of categories of the modes of action known; e.g. 1. inhibitors of nucleic acid bio­synthesis either at the level of the template or by some other mechanisms, 2. inhi­bitors of protein synthesis at the ribosomal or translational level, 3. interference with the formation or integrity of the cell wall or membrane, 4. inhibition of specific enzyme reactions in the intermediary metabolism of the cell. Because of the paucity of subject material, the last two topics are arranged as one unit together with some miscellaneous subjects where significant knowledge has yet to lead to an unambiguous decision regarding the mode of action.

The Editors have included, indeed encouraged, consideration of antimicrobial agents which are not or may never be useful clinical chemotherapeutic agents. This is done without apology since such agents illustrate general principles of the interaction of antimicrobial drugs with either the host or infectious cell and indeed much of our present knowledge of molecular biology and antibiotic action has come from the study of such substances.

In summary, the Editors wish to thank their throughout-the-world colleagues for innumerable instances of help and advice during the conception, planning and preparation of Volume III in the series Antibiotics. They apologize for the obvious omissions of desirable new chapters (e.g. quinine, nitrofurans, para­aminosalicylic acid etc.) and for the lack of updated treatments of certain more familiar substances (e.g. actinomycin, chromomycin, hadacidin, rubiflavin, streptonigrin etc.). When primary authorities could not be enlisted we have decided in favor of deferral to a future new volume on the Mode of Action of Antibiotics. Like the editors of Volumes I and II we have attempted to maintain the highest standards for authorship and editorial review. It is for you, the intended recipient of this our most sincere effort to evaluate the result.

Chicago/Washington, Summer 1974 JOHN W. CORCORAN

FRED E. HAHN

Acknowledgements

Preparation of this third volume in the series on antibiotics published by Springer Verlag was begun under the editorship of Professor J. F. SNELL. With his being unable to continue in this effort, the responsibility was assumed by the present editors. They wish to express their deep appreciation to Dr. KONRAD F. SPRINGER for his continued interest, encouragement and understanding during the long period of planning and the recent period of manuscript pleparation. Above all, the editors wish to thank their colleague Dr. KAsTURI LAL ARORA for his extraordinary support in the detailed preparation of this volume. Dr. ARORA carefully surveyed the abstract and original literature and advised them during the planning phase for this work and again during the period of manuscript prepara­tion and review he helped immeasurably in the maintenance of contact with both authors and publisher. His painstaking and scholarly review of each manuscript prior to submission to one or the other of the editors made their task much simpler and permitted the review process to focus on the scientific aspects of each chapter. The support of Dr. ARORA has made this volume a reality.

Contents

Section I. Interference with Nucleic Acid Biosynthesis

Anthramycin. KURT W. KOHN. (With 6 Figures). . . . . . . . . 3 3'-Amino-3'-Deoxyadenosine. HAROLD T. SHIGEURA. (With 1 Figure) 12 Bleomycin. HAMAO UMEZAWA. (With 2 Figures). . . . . . . . . . 21 Berenil: A Trypanocide with Selective Activity against Extranuclear DNA.

B. A. NEWTON. (With 7 Figures) . . . . . . . . . . 34 Camptothecin. SUSAN B. HORWITZ. (With 3 Figures). . . . . 48 Chloroquine (Resochin). FRED E. HAHN. (With 3 Figures) . . 58 Distamycin A and Netropsin. FRED E. HAHN. (With 5 Figures) 79 Daunomycin (Daunorubicin) and Adriamycin and Structural Analogues: Biological Activity and Mechanism of Action. A. DI MARCO, F. ARCAMONE,

and F. ZUNINO. (With 12 Figures) . . . . . . . " . . 101 Edeines. Z. KURYLO-BoROWSKA. (With 6 Figures). . . . . . 129 Ethidium and Propidium. MICHAEL WARING. (With 7 Figures) 141 Kanchanomycin. IRVING H. GOLDBERG. (With 9 Figures) . 166 Nalidixic Acid - Mode of Action. WILLIAM A. Goss and THOMAS M.

COOK. (With 8 Figures). . . . . . . . . . . . . . . . . . . . . . 174 Olivomycin, Chromomycin, and Mithramycin. G. F. GAUSE. (With 2 Figures) 197 Quinacrine and Other Acridines. ALAN DAVID WOLFE. (With 1 Figure) ... 203 Quinoxaline Antibiotics. KEN KATAGIRI, TADASHI YOSHIDA, and KOSABURO

SATO. (With 5 Figures). . . . . . . . . . . . . . . . . . . 234 Rifamycins and Other Ansamycins. W. WEHRLI and M. STAEHELIN. (With

4 Figures). . . . . . . . . . . . . . . . . . . . . . . . . 252 Sibiromycin. G. F. GAUSE. (With 2 Figures) . . . . . . . . . . . 269 Thiaxanthenones: Miracil D and Hycanthone. ERICH HIRSCHBERG. (With

2 Figures). . . . . . . . . . . . . . . . . . . . . . . . . .. 274 Trimethoprim and Pyrimethamine. JAMES J. BURCHALL. (With 3 Figures) . 304

Section n. Interference with Protein Biosynthesis

Althiomycin. SIDNEY PESTKA. (With 1 Figure) ............. 323 Aurintricarboxylic Acid. A Non-Antibiotic Organic Molecule that Inhibits

Protein Synthesis. DAVID APIRION and DENNIS DOHNER. (With 1 Figure) 327 Aminoglycoside Antibiotics. NOBUO TANAKA. (With 11 Figures) 340 Borrelidin. K. PORALLA. (With 2 Figures) . . . . 365 Chloramphenicol. SIDNEY PESTKA. (With 6 Figures) . . . . . . 370

VIII Contents

The Erythromycins. NANCY L. OLEINICK. (With 1 Figure) . . . . . . . . 396 Emetine and Related Alkaloids. ARTHUR P. GROLLMAN and ZELDA J ARKOVSKY.

(With 5 Figures). . . . . . . . . . . . . . 420 Fusidic Acid. NOBUO TANAKA. (With 4 Figures) 436 Gougerotin. MUNEHIKO YUKIOKA. (With 6 Figures) . . . 448 The Macrolide Antibiotics. D. VAZQUEZ. (With 2 Figures) 459 Micrococcin and Micrococcin P. SIDNEY PESTKA. (With 2 Figures) . 480 Mikamycin. NOBUO TANAKA. (With 5 Figures) . . . 487 Pactamycin. IRVING H. GOLDBERG. (With 12 Figures) . . . . . . 498 Primaquine. JOHN G. OLENICK. (With 1 Figure) . . . . . . . . . 516 The Streptogramin Family of Antibiotics. D. VAZQUEZ. (With 2 Figures) . 521 Streptomycin, Dihydrostreptomycin, and the Gentamicins. DAVID

SCHLESSINGER and GERALD MEDOFF. (With 2 Figures). . . . . . .. 535 The Thiostrepton Group of Antibiotics. SIDNEY PESTKA and JAMES W. BODLEY.

(With 6 Figures). . . . . . . . . . . . . . . . . . . . . . . . . 551

Section ID. Interference with Cell Wall/Membrane Biosynthesis, Specific Enzyme Systems and Those in Which Mode of Action Not Known with Certainty

Berberine. FRED E. HAHN and JENNIE OAK. (With 1 Figure) 577 Boromycin. W. PACHE. (With 2 Figures) . . . . 585 Colicins 1972. LOUIS W. WENDT. . . . . . . . . . . . . 588 Griseofulvin. FLOYD M. HUBER. (With 1 Figure) . . . . . 606 Irehdiamine and Malouetine. SIMON SILVER, LOUIS WENDT, and PINAKILAL

BHATTACHARYYA. (With 1 Figure) . . . . . . . . . . . . . . 614 Isonicotinic Acid Hydrazide. C. R. KRISHNA MURTI. (With 4 Figures) 623 Sideromycins. F. KNUSEL and W. ZIMMERMANN. (With 11 Figures) . 653 Sulfonamides and Sulfones. NITYA ANAND. (With 12 Figures) 668 Suramin. JOHN G. OLENICK. (With 1 Figure) . . . . . . . . . . 699 Vancomycin. D. C. JORDAN and P. E. REYNOLDS. (With 3 Figures) 704

Subject Index . . . . . . . . . . . . . . . . . . . . . . . 719

Contributors

NITYA ANAND, Division of Medicinal Chemistry, Central Drug Research Institute, Lucknow/India

DAVID APIRION, Department of Microbiology, Washington University Medical School, St. Louis, Missouri 63110/USA

F. ARCAMONE, Istituto Ricerche Di Base Farmitalia, Milano/Italy

PINAKILAL BHATTACHARYYA, Department of Biology, Washington University, St. Louis, Missouri 63130/USA

JAMES W. BODLEY, Department of Biochemistry, University of Minnesota, Min­neapolis, Minnesota 55455/USA

JAMES J. BURCHALL, The Wellcome Research Laboratories, Burroughs Wellcome Co., 3030 Cornwallis Road, Research Triangle Park, North Carolina 27709/USA

JENNIE CIAK, Department of the Army, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington, D. C. 200l2/USA

THOMAS M. COOK, Department of Microbiology, University of Maryland, College Park, Maryland 20742/USA

A. DI MARCO, Division of Experimental Oncology B, Istituto Nazionale Per Lo Studio E La Cura Dei Tumori, Via Venezian, 1,20133 Milano/Italy

DENNIS DOHNER, Department of Microbiology, Washington University Medical School, St. Louis, Missouri 631l0/USA

G. F. GAUSE, Institute of New Antibiotics, Bolshaia Pirogovskaia, 11, Moscow/ USSR

IRVING H. GOLDBERG, Department of Pharmacology, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115/USA

WILLIAM A. Goss, Sterling-Winthrop Research Institute, Division of Sterling Drug Inc., Rensselaer, New York 12144/USA

x Contributors

A. P. GROLLMAN, Department of Pharmacology, Albert Einstein College of Medi­cine of Yeshiva University, 1300 Morris Park Avenue, Bronx, New York 10461/ USA

FRED E. HAHN, Department of Molecular Biology, Walter Reed Army Institute of Researt;:h, Walter Reed Army Medical Center, Washington, D. C. 20012/USA

ERICH HIRSCHBERG, College of Medicine and Dentistry of New Jersey, New Jersey Medical School, 100 Bergen Street, Newark, New Jersey 07l03/USA

SUSAN B. HORWITZ, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, New York 1046l/USA

FLOYD M. HUBER, Antibiotic Fermentation Technology, Eli Lilly and Company, Indianapolis, Indiana 46206/USA

Z. JARKOVSKY, Department of Pharmacology, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, New York 10461/USA

D. C. JORDAN, Department of Microbiology, College of Biological Science, Univer­sity of Guelph, Guelph, Ontario/Canada

KEN KATAGIRI, Shionogi Research Laboratory, Shionogi and Co., Ltd., Fukushima-ku, Osaka 553/Japan

F. KNUSEL, Biological Research Laboratories, Pharmacology Division, Ciba­Geigy, Ltd., 4002 Basel/Switzerland

KURT W. KOHN, National Cancer Institute, Department of Health, Education, and Welfare, Public Health Service, National Institutes of Health, Bldg. 37, Rm. 5B27, Bethesda, Maryland 200l4/USA

C. R. KRISHNA MURTI, Division of Biochemistry, Central Drug Research Institute, Lucknow/India

Z. KURYLO-BoROWSKA, Department of Biochemistry, The Rockefeller University, New York, 1002l/USA

GERALD MEDOFF, Departments of Microbiology and Medicine, Infectious Disease Division, Washington University School of Medicine, S. Louis, Missouri 63110/ USA

B. A. NEWTON, Medical Research Council, Biochemical Parasitology Unit, Molteno Institute, University of Cambridge, Cambridge/Great Britain

Contributors XI

NANCY L. OLEINICK, Departments of Radiology and Biochemistry, Case Western Reserve University, School of Medicine, 2220 Circle Drive, Cleveland, Ohio 44106/ USA

JOHN G. OLENICK, Department of Molecular Biology, Department of the Army, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington, D. C, 20012/USA

W. PACHE, Pharmaceutical Division, Chemical Research, Sandoz Ltd. 4002 Basel/ Switzerland

SIDNEY PESTKA, Roche Institute of Molecular Biology, Nutley, New Jersey 07110/ USA

KARL PORALLA, Lehrstuhl fUr Mikrobiologie II der Universitat Tiibingen, Berg­hof, 7400 Tiibingen-Lustenau/Fed. Rep. Germany

P. E. REYNOLDS, Sub-department of Chemical Microbiology, Department of Biochemistry, University of Cambridge/Great Britain

KOSABURO SATO, Shionogi Research Laboratory, Shionogi and Co., Ltd., Fukushima-ku, Osaka 553/Japan

DAVID SCHLESSINGER, Departments of Microbiology and Medicine, Infectious Disease Division, Washington University School of Medicine, st. Louis, Missouri 63110/USA

HAROLD T. SHIGEURA, Merck Institute for Therapeutic Research, Rahway, New Jersey 07065/USA

SIMON SILVER, Department of Biology, Washington University, St. Louis, Missouri 63130/USA

M. STAEHELIN, Ciba-Geigy AG, Bau 125/717 Klybeck, 4000 Basel/Switzerland

NOBUO TANAKA, Institute of Applied Microbiology, The University of Tokyo, Bunyko-ku, Tokyo/Japan

HAMAO UMEZAWA, Microbial Chemistry Research Foundation, Institute of Microbial Chemistry, 14-23 Kamiosaki 3-Chrome, Shinagawa-ku, Tokyo/Japan

DAVID VAZQUEZ, C.S.I.e. Centro De Investigaciones Bioiogicas, Instituto De Biologia Celular, Velazquez, 144, Madrid-6/Spain

XII Contributors

MICHAEL WARING, University of Cambridge, Department of Pharmacology, Medical School, Hills Road, Cambridge/Great Britain

WALTER WEHRLI, Ciba-Geigy AG, Bau 125/717 Klybeck, 4000 Basel/Switzerland

LOUIS W. WENDT, Department of Biology, Montana State University, Bozeman, Montana 59715/USA

ALAN DAVID WOLFE, Department of Molecular Biology, Walter Reed Army Insti­tute of Research, Washington, D.C. 20012/USA

TADASHI YOSHIDA, Shionogi Research Laboratory, Shionogi and Co., Ltd., Fukushima-ku, Osaka 553/Japan

MUNEHIKO YUKIOKA, Department of Biochemistry, Osaka City University Medical School, 1-4-54, Asahi-machi, Abeno-ku, Osaka 545/Japan

W. ZIMMERMANN, Biological Research Laboratories, Pharmacology Division, Ciba-Geigy, Ltd., 4002 Basel/Switzerland

F. ZUNINO, Division of Experimental Oncology B, Istituto Nazionale Per Lo Studio E La Cura Dei Tumori, Via Venezian, 1,20133 Milano/Italy