“Fae REGULATIONS
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CHEMISTRY-III
Dr. IC. G. BOTHARA
PRAKASHAN Raotshs c-#
A TEXT BOOK OF
MEDICINAL
CHEMISTRY-III
As Per PCI Regulations
For
Third Year B. Pharm.
Semester - v1
K. G. BOTHARA
M. Pharm. Ph, D.
Principal and Professor
Sinhgad Institute of Pharmacy,
Narhe, Pune - 411 041,
Price % 225.00
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fication OLB! PREFACE
PREFACE,
In the last two decades, the phases of ever-growing volume and ever-changing nature of
the drug information in the field of antibiotics, antibacterials and antifungal agents are
witnessed. This is mainly due to an increase in the rate of introduction of new drugs and an
increase in the number and depth of published work on both, new as well as existing drugs.
Above facts necessitated addition of all recent information wherever it deserves, while
presenting the first edition of this book.
The book was appreciated in all corners of the profession. It has now attained the
veputation as a class-room text book for undergraduate and post-graduate students of pharmacy.
fowever, our aim remains the same as to present a review. of basic principles of medicinal
hemistry and to explain the effects of structural modifications of the lead nucleus on the
lectivity of action, duration of action and on the intensity and frequency of adverse-effects.
Each chapter is revised thoroughly to meet the needs of future facts and fantacies. Since
is book is written basically for degree students, a backbone understanding in basic disciplines
assumed.
I wish to place on record my sincere thanks to the publisher Mr. D. K. Furia for his kind
peration. | am greatly indebted to my colleagues for their generous help and criticism. I also
110 acknowledge indebtedness to all who have assisted for the completion of the book.
Suggestions from all corners of the profession are welcome. I am responsible for any
iencies or errors that might have remained and would be grateful if readers would call them
‘attention.
Author (08 Hira:
uNITIV
see photericin-B, Nystatin, N
antifungal antibiotics: Ampho' icin-B, Nystatin, Natamycin, Griseofulvin. S
— agents: Clotrimazole, Econazole, Butoconazole, Oxiconazole Tloconeret
Ketoconazole, Terconazole, Itraconazole, Fluconazole, Naftifine hydrochlonge
Miconazole,
Toinaftate*.
: Metronidazole’, Tinidazole, Ornidazole, Diloxanide, lodoquingy
Anti-protozoal Agents:
Pentamidine Isethionate,
Antheimintics: Diethyicarbamazine citrate’,
Niclosamide, Oxamniquine, Praziquantal, Ivermectin,
Sulphonamides and Sulfones
Historical development, chemistry, classification and SAR of Sulfonamides: Sulphamethizojg
Sulfacetamide*, Sulphapyridine, Sulfamethoxaolg:
Sulfisoxazole, Sulphamethizine,
Sulphadiazine, Mefenide acetate, Sulfasalazine.
Folate reductase Inhibitors: Trimethoprim”, Cotrimoxazole.
Atovaquone, Eflornithine,
Thiabendazole, Mebendazole*, Albendazol,
Sulfones: Dapsone”.
(07 Hrs,
UNIT V
Introduction to Drug Design
Various approaches used in drug design.
rameters used in quantitative structure activity relationship (QSAR) suc!
fer and Hanse!
Physicochemical pal
as partition coefficient, Hammet's electronic parameter, Tafts steric paramet
analysis.
Pharmacophore modeling and docking techniques.
Combinatorial Chemistry: Concept and applications chemistry: solid phase and solutio
phase synthesis of combinatorial
deeded _————__conrents
Antiblotics-!
GE
2. Antiblotics-Il
3. Modes of Action of Antibiotics
4. Prodrugs
5. Antimalarials
6. Antl-Tubercular Agents
7. Urinary Tract Antl-infective Agents.
8. Antiviral Agents
UNIT - iV
9. Antifungal Agents
10. Antlprotozoal Agents
11, Anthelmintics
12. Sulphonamides and Sulfones
UNIT
13, Introduction to Drug Design
Index
14-130
24-26
3.1-3.18
41-412
51-516
6.1-6.10
TA-7.10
81-819
91-9,
10.1 - 10.14
11.4-11.9
124-1216
13.1 - 13.48
Ma-14 UNITI
Chapter...1
ANTIBIOTICS
SS
¢ SYNOPSIS ¢
1.1 INTRODUCTION :
1.2. CLASSIFICATION .6 AMINOGLYCOSIDE ANTIBIOTICS
1.3 B-LACTAM ANTIBIOTICS
1.7 BACTERAL RESISTANCE AND RECENT
1.4 HYPERSENSITIVITY OR ALLERGIC ‘TRENDS IN DRUG DESIGN OF AMINO
REACTIONS GLYCOSIDE ANTIBIOTICS
15 CEPHALOSPORINS 1.8 TETRACYCLINE ANTIBIOTICS
—_———
[1.4 INTRODUCTION
The term chemotherapy can be defined as ‘the treatment of diseases caused due to
infective parasites or organisms without causing destruction of their animal host’. Modern
chemotherapy began with the work of Paul Ehrlich (1854 - 1915). Due to his pioneer
discoveries in this field, he is regarded as “Father of Chemotherapy".
The second phase of revolution emerged in the 1930's (following the discovery of the
British bacteriologist Alexander Fleming when he tested the filtrate of a broth culture of a
penicilium mold for its antibacterial activity.
The term antibiotic has its origin in the word antibiosis (i.e. against life); the latter being
first time used by Vuillemin in 1889 in an attempt to describe the concept of survival of the
e discovery of penicillin is named after Sir Fleming in 1928, it was not until
‘ed it and described its
fittest. Although th
1940 at Oxford that Florey and Chain and their associates isolat!
properties in detail, and thus turning Fleming's discovery to practical significance.
term antibiotic, the most appropriate one may
\d derived from or metabolically produced
the growth and/or the survival of
f differences amongst the
antibacterial spectra
Among the many attempts to define the
be stated as "An antibiotic is a chemical compoun
by microorganism and that in high dilution antagonizes
icroorganisms". The probable points o}
hemical and pharmacological properties,
one or more species of mi
antibiotics may be physical, cl
and mechanism of action.
(1.1) Antibio
Medicinal Chemistry-M tee
: ——_}
(i) Depending upon clinical effectiveness, spectrum of activity = oe re
those inhibiting only one group of microorganism are calle i as Hei _ a i er
eg. nystatin and bacitracin. These antibiotics exhibit a high ae saith ake . .
antibiotics inhibit both gram-positive and gram-negative bacteria a a le lular
organism may be termed as broad spectrum antibiotics €.9. phe and
tetracyclines.
(ii) Depending upon the sources from which antibiotics are obtained they can be
classified as follows:
(a) Natural: These antibiotics are obtained from the large scale fermentation of
microorganisms. e.g. bacitracin and polymixin are obtained from some bacilli while
streptomycin, tetracyclines etc. from streptomyces species.
(b) Semisynthetic: The observation that 6-aminopenicillanic acid can be obtained from
cultures of P. chrysogenum that were depleted of side chain precursors led to the
development of this class. For example, during the commercial production of benzyl
penicillin (Penicillin G), phenylacetic acid is added to the medium in order to achieve
predominance of the product.
(©) Synthetic: This class includes antibiotics which are having purely synthetic origin.
For example, Chloramphenicol, a broad spectrum antibiotic initially isolated from a
fermented media in 1947 and later was produced synthetically on a commercial
basis.
(i) The third basis of classification involves the differences in mechanism of action,
accordingly these agents can be divided as:
(a) Drugs that interfere with the biosynthesis of bacteri
Cephalosporins, Cycloserine, Bacitracin and Vancomycin,
(b) Drugs that interfere in the functionin i ix
; 19 of cytoplasmic . Polymixins
Amphotericin B and Nystatin, 7 oo
ial cell-wall e.g. Penicillins,
(©) Drugs that interfere with the pi
Tetracyclines, and Chlorampheni
(d) Drugs that interfere with th ic acid bi i
Sete © nucleic acid biosynthesis €g. Actinomycin, Griseoful”
rotein biosynthesis
4g. Erythromycin, Lincomycins
icol and
(iv) Antibiotics can be in general classified as:
(A) B-lactam antibiotics
(B) Aminoglycoside antibioti
antibiotics
(a) Tetracycline antibiotics (D) Peptide a tibioti a
(€) Macrolide antibiotics ie
(F) Li
(6) Unclassified antibiotics oD
