BENGAL SCHOOL OF TECHNOLOGY

SUGANDHA, DELHI ROAD, CHINSURAH,

HOOGHLY, WEST BENGAL-712102.

REPORT WRITING

ON

TITLE OF THE TOPIC: DRUG DISCOVERY BY SERENDIPITY

SUBMITTED BY:

NAME: Debkantha Gope

COURSE: M.pharm YEAR/SEMESTER: 1st Year 2st Semester

ROLL NO: 19320222008 REGISTRATION NO: : 221932310020 OF

2022-23

SUBJECT: PRINCIPLES OF DRUG DISCOVERY

SUBJECTCODE: MPT2083

ACADEMIC SESSION: 2022-23

DATE OF SUBMISSION:8.3.23
Drug discovery by serendipity
Serendipity is not merely stumbling on things unsought for, it is the ability to see significances
and find values in the things stumbled upon. Serendipity means an aptitude for making
desirable discoveries by accident. It was found that the discovery of 5.8% (84/1437) of all drugs
on the market involved serendipity. Of these drugs, 31 (2.2%) were discovered in the laboratory
and 53 (3.7%) were discovered in a clinical setting. In addition, 263 (18.3%) of the
pharmaceuticals in clinical use today are chemical derivatives of the drugs discovered with the
aid of serendipity. Therefore, in total, 24.1% (347/1437) of marketed drugs can be directly
traced to serendipitous events confirming the importance of this elusive phenomenon. In the
case of anticancer drugs, 35.2% (31/88) can be attributed to a serendipitous event, which is
somewhat larger than for all drugs. Recently a new concept of Known Drug Space (KDS) has
been developed to help drug designers to navigate chemical space based on the analysis of
drugs in clinical use. It is known that 10% of KDS are unaltered natural products and 29% are
their derivatives (semi-synthetics). The therapeutic field that has benefited the most from
serendipity is central nervous system active drugs reflecting the difficulty in designing
compounds to pass the blood-brain-barrier and the lack of laboratory-based assays for many of
the diseases of the mind.

In general, 24% of all pharmaceuticals currently on the market were affected in a positive way
during their development by this phenomenon with CNS active drugs being the most
prominent. This leads to the conclusion that drug discovery is based on good science and where
intuition, critical thinking, sagacity and open-mindedness play crucial roles.
STATISTICS:
It was found that the discovery of 5.8%
(84/1437) of all drugs on the market
involved serendipity. Of these drugs, 31
(2.2%) were discovered in the
laboratory and 53 (3.7%) were
discovered in a clinical setting. In
addition, 263 (18.3%) of the
pharmaceuticals in clinical use today

are chemical derivatives of the drugs discovered with the aid of serendipity. Therefore, in total,
24.1% (347/1437) of marketed drugs can be directly traced to serendipitous events confirming
the importance of this elusive phenomenon. In the case of anticancer drugs, 35.2% (31/88) can
be attributed to a serendipitous event, which is somewhat larger than for all drugs

The distribution of the serendipity types (laboratory-based and clinical) and their chemical
derivatives in clinical use (100%= 1437).

Steps of drug discovery:

SERENDIPITOUS DRUG ACTS ON CARDIOVASCULAR
SYSTEM:
During the 1920's, cattle began to mysteriously die from internal hemorrhage. The cause was
attributed generally to spoiled sweet clover, but when the Great Depression hit and ranchers
could ill afford to lose a single cow, one frustrated farmer, Ed Carlson, packed up his dead cow
along with a milk can filled with blood that refused to clot and drove to the Wisconsin Alumni
Research Foundation (WARF) looking for answers. There researcher Karl Link was able to
isolate the naturally occurring chemical compound coumarin, which, when oxidized in damp

hay, is the culprit anticoagulant. In 1945, Link came up with the idea to use the compound as
a rodenticide, as it is still used today. Scientists continued to study and test coumarin.

In 1955, it was given to President Dwight Eisenhower after a myocardial infarction and today
- from cattle- killer, to rat-killer, to human life-saver - Warfarin is the most widely used
anticoagulant in the world.

SERENDIPITOUS ANTIBIOTIC DRUG:

Alexander Fleming didn't clean up his workstation before going on vacation one day in 1928.
When he came back, Fleming noticed that there was a strange fungus on some of his cultures.
Even stranger was that bacteria didn't seem to thrive near those cultures.
Penicillin became the first and is still one of the most widely used antibiotics.

In 1928, Scottish Scientist Sir Alexander Fleming was

studying Staphylococcus - the bacteria that causes food
poisoning.He turned up at work one day and discovered a
blue-green mould that seemed to be inhibiting growth of
the bacteria. He grew a pure culture of the mould and
Discovered that it was a Penicillium mould.

SERENDIPITOUS ANTI DIABETIC DRUG

Often several serendipitous discoveries contribute to the establishment of a major therapy.

Take for example insulin for diabetes. Chance observation of flies attracted to the sugar-rich
urine of experimental dogs with pancreas removed led to the discovery that the pancreas is
causally related to diabetes.

Since that discovery in 1889, many scientists tried to extract the pancreas' secretion and use it
as a remedy for diabetes. Some almost made it; others failed, but not necessarily because they
were more ignorant.

When Frederick Banting, Charles Best, and John Macleod succeeded to extract insulin and
demonstrate its therapeutic efficacy in 1921, they designed their crucial experiment on a wrong
conception.

SERENDIPITOUS ANTICANCER DRUG

Nearly all the great discoveries in chemotherapy have been made as a result of a false
hypothesis or due to a so-called chance observation.

Chemotherapy involves the use of low-molecular-weight drugs to selectively destroy a tumor

or at least limit its growth.

Nitrogen mustards were the first agents to be used clinically. Their use resulted from the
accidental discovery that the mustard gas used in world war II had antileukemic properties.
Since then, important advances have been made in the development of new anticancer drugs.
For example, cisplatin, which was also discovered serendipitously, provided a major advance
in the treatment of testicular and ovarian carcinomas.

The discovery of cis-platin was serendipitous. In 1965, Rosenberg was looking into the effects
of an electric field on the growth of Escherichia coli bacteria. He noticed that bacteria ceased
to divide when placed in an electric field but what Rosenberg also observed was a 300-fold
increase in the size of the bacteria.

He attributed this to the fact that somehow the platinum-conducting plates were inducing cell
growth but inhibiting cell division. It was later deduced that the platinum species responsible
for this was cis-platin.

Rosenberg hypothesized that if cis-platin could inhibit bacterial cell division it could also stop
tumor cell growth. This conjecture has proven correct and has led to the introduction of cis-
platin in cancer therapy. Indeed, in 1978, six years after clinical trials conducted by the NCI
and Bristol-Myers Squibb, the U.S. Food and Drug Administration (FDA) approved cis- platin
under the name of Platinol for treating patients with metastatic testicular or ovarian cancer in
combination with other drugs but also for treating bladder cancer.

Cisplatin is a chemotherapy drug commonly prescribed to lung cancer patients. Because it is

administered systemically, the entire body gets a
hefty dose of the toxic substance with side effects
that are often quite debilitating. To better target
the drug toward lung CA, researchers at the
University of Strachlyde, Glasgow and
TRANSAVE (Monmouth Junction, NJ) have
independently developed inhalation
microcapsules that can contain cisplatin.

SERENDIPITOUS DRUG USED IN MYOCARDIAL INFARCTION:

A serendipitous discovery by William Smith Tillett in 1933, followed by many years of work
with his student Sol Sherry, laid a sound foundation for the use of streptokinase as a
thrombolytic agent in the treatment of acute myocardial infarction.
The drug found initial clinical application in combating fibrinous pleural exudates,
hemothorax, and tuberculous meningitis.

In 1958, Sherry and others started using streptokinase

in patients with acute myocardial infarction and
changed the focus of treatment from palliation to
"cure."

Effects of serendipity in drug discovery

• Encourages to do more researches

• Many drugs were discovered and many are expected to come
• Starting of antibiotics
• New era against cancer treatment; 35.2% anticancer drugs were serendipitously
discovered Changes the focus of research to effective results
• Therapeutic field (specially CNS drugs) is being benefited greatly

CURRENT STATUS OF SERENDIPITY

Several putative "anti-serendipity" factors that may interfere with current drug development
have been identified.

These include 1) movement toward rational drug design based on translational research, 2)
reduction in the amount of time that clinicians have to observe patients, and 3) reliance on the
double-blind placebo control design to demonstrate efficacy...

The trend toward rational drug design is clear. However, its relationship to serendipity is
opaque. Rational drug design guided by translational research refers to the development of
drugs deliberately designed to alter processes that have been implicated in mental pathology
by basic research

Another putative "anti-serendipity" factor is a constriction in the amount of time that clinical
researchers have to observe drug effects. Interestingly, this has been linked to the closing of
long-term care mental hospitals (ie., deinstitutionalization)

Another putative "anti-serendipity" factor is the use of the double blind placebo control design.
The principal objection to this design is that the design does not allow for analysis of individual
differences in drug response.

The therapeutic field that has benefited the most from serendipity is central nervous system
active drugs reflecting the difficulty in designing compounds to pass the blood-brain-barrier
and the lack of laboratory-based assays for many of the diseases of the mind.

CONCLUSION:
In general, 24% of all pharmaceuticals currently on the market were affected in a positive way
during their development by this phenomenon with CNS active drugs being the most
prominent. This leads to the conclusion that drug discovery is based on good science and where
intuition, critical thinking, sagacity and open-mindedness play crucial roles

Reference:
• The role of serendipity in drug discovery - Thomas A.Ban, MD, FRCP Vanderbilt
University, Nashville, USA
• Serendipity and New Drugs for Infectious Disease, William C. Campbell
• Systemizing Serendipity for Cardiovascular Drug discovery, Peter J. Schlueter and
Randall T. Peterson
• The effect of Serendipity in Drug Discovery and Development - Emily Hargrave-
Thomas, Bo Yu and Johannes Reynisson, Chemistry in New Zealand, January 2012