An assignment on natural products as

chemotherapeutics.

Name:Md. Anwarul Haque

Department of Biochemistry and molecular
biology,MBSTU.
Course code:BMB- 3209.
ID:BMB-17025.
Session:2016-2017
Definition of Natural products
A natural product is a chemical compound or substance produced by a living organism –
found in nature that usually has a pharmacological or biological activity for use in
pharmaceutical drug discovery and drug design. A natural product can be considered as
such even if it can be prepared by total synthesis. These small molecules provide the
source or inspiration for the majority of FDA-approved agents and continue to be one of
the major sources of inspiration for drug discovery. In particular, these compounds are
important in the treatment of life-threatening conditions.

What is chemotherapy?
Chemotherapy is a drug treatment that uses powerful chemicals to kill fast-growing
cells in your body.

Chemotherapy is most often used to treat cancer, since cancer cells grow and multiply much
more quickly than most cells in the body. 

Many different chemotherapy drugs are available. Chemotherapy drugs can be used alone
or in combination to treat a wide variety of cancers.

Though chemotherapy is an effective way to treat many types of cancer, chemotherapy

treatment also carries a risk of side effects. Some chemotherapy side effects are mild and
treatable, while others can cause serious complications.

Introduction to chemotherapeutics:

The term chemotherapy has come to connote non-specific usage of

intracellular poisons to inhibit mitosis, cell division. The connotation excludes more
selective agents that block extracellular signals (signal transduction). The development
of therapies with specific molecular or genetic targets, which inhibit growth-
promoting signals from classic endocrine hormones (primarily estrogens for breast
cancer and androgens for prostate cancer) are now called hormonal therapies. By
contrast, other inhibitions of growth-signals like those associated with receptor
tyrosine kinases are referred to as targeted therapy.

Importantly, the use of drugs (whether chemotherapy, hormonal therapy or targeted

therapy) constitutes systemic therapy for cancer in that they are introduced into the
blood stream and are therefore in principle able to address cancer at any anatomic
location in the body. Systemic therapy is often used in conjunction with
othermodalitiesthat constitute local therapy(i.e. treatments whose efficacy is confined
to the anatomic area where they are applied) for cancer such as radiation
therapy, surgery or hyperthermia therapy.
Traditional chemotherapeutic agents are cytotoxic by means of interfering with cell
division (mitosis) but cancer cells vary widely in their susceptibility to these agents.
To a large extent, chemotherapy can be thought of as a way to damage or stress
cells, which may then lead to cell death if apoptosis is initiated.

Natural products as chemotherapeutics:

Over 60% of the current anticancer drugs were derived in one way or another from natural
sources [3]. Nature continues to be an abundant source of biologically active and diverse
chemotypes, and while relatively few of the actual isolated natural products are developed
into clinically effective drugs in their own right, these unique molecules often serve as
models for the preparation of more efficacious analogues and prodrugs through the
application of chemical methodology, such as total or combinatorial (parallel) synthesis, or
the manipulation of biosynthetic pathways. In addition, improvements in formulation may
result in more effective administration of the drug to patients, or conjugation of toxic natural
molecules to monoclonal antibodies or polymeric carriers specifically targeting epitopes on
tumors of interest can lead to the development of efficacious targeted therapies. The essential
role played by natural products in the discovery and development of novel anticancer agents,
and the importance of multidisciplinary collaboration in the optimization of novel molecular
leads from natural product sources have been extensively reviewed [4,5,6,7,8,9]. 
The following sections briefly discuss some of the recent developments in this area, with
discussions limited to new agents currently in some stage of advanced clinical development,
or agents which have been approved for commercial use. It should be noted that effective
cancer chemotherapy often involves the use of combinations of several agents (so-called
combination chemotherapy), and these combination regimens can comprise agents derived
from both natural and synthetic sources. Interested readers may gain information on recently
completed and ongoing clinical trials of agents discussed below (e.g., vinblastine,)
Natural products in modern life sciences:

With a realistic threat against biodiversity in rain forests and in the sea, a sustainable use of
natural products is becoming more and more important. Basic research directed against different

organisms in Nature could reveal unexpected insights into fundamental biological mechanisms
but also new pharmaceutical or biotechnological possibilities of more immediate use. Many
different strategies have been used prospecting the biodiversity of Earth in the search for novel
structure-activity relationships, which has resulted in important discoveries in drug development.
However, we believe that the development of multidisciplinary incentives will be necessary for a
future successful exploration of Nature. With this aim, one way would be a modernization and
renewal of a venerable proven interdisciplinary science, Pharmacognosy, which represents an
integrated way of studying biological systems. This has been demonstrated based on an
explanatory model where the different parts of the model are explained by our ongoing research.
Anti-inflammatory natural products have been discovered based on ethnopharmacological
observations, marine sponges in cold water have resulted in substances with ecological impact,
combinatory strategy of ecology and chemistry has revealed new insights into the biodiversity of
fungi, in depth studies of cyclic peptides (cyclotides) has created new possibilities for engineering
of bioactive peptides, development of new strategies using phylogeny and chemography has
resulted in new possibilities for navigating chemical and biological space, and using bioinformatic
tools for understanding of lateral gene transfer could provide potential drug targets. A
multidisciplinary subject like Pharmacognosy, one of several scientific disciplines bridging biology
and chemistry with medicine, has a strategic position for studies of complex scientific questions
based on observations in Nature. Furthermore, natural product research based on intriguing
scientific questions in Nature can be of value to increase the attraction for young students in
modern life science.

Natural products in drug discovery:

Natural products have been the single most productive source of leads for
the development of drugs. Over a 100 new products are in clinical
development, particularly as anti-cancer agents and anti-infectives.
Application of molecular biological techniques is increasing the availability
of novel compounds that can be conveniently produced in bacteria or
yeasts, and combinatorial chemistry approaches are being based on natural
product scaffolds to create screening libraries that closely resemble drug-
like compounds. Various screening approaches are being developed to
improve the ease with which natural products can be used in drug discovery
campaigns, and data mining and virtual screening techniques are also being
applied to databases of natural products. It is hoped that the more efficient
and effective application of natural products will improve the drug
discovery process.

Pathway of natural products:

Natural products for cancer chemotherapy:

Natural products have been the mainstay of cancer chemotherapy for the
past 30 years. However, the quickening pace of (aberrant) gene
identification, and the new technologies of combinatorial chemistry and
high-throughput screening, should provide access to a wide range of new,
totally synthetic drugs. Will these new approaches sound the death knell
for therapies based on natural products? In reality, natural products are
likely to provide many of the lead structures, and these will be used as
templates for the construction of novel compounds with enhanced
biological properties.

Some plant anti tumour products:

Camptotheca acuminata
The cancer treatment drug topotecan is a synthetic chemical compound similar in
chemical structure to camptothecin which is found in extracts of Camptotheca (happy
tree).[7]
Catharanthus roseus
Vinca alkaloids were originally manufactured by extracting them
from Catharanthus (Madagascar Periwinkle).[1]
Podophyllum spp.
Two chemotherapy drugs, etoposide and teniposide, are synthetic chemical
compounds similar in chemical structure to the toxin podophyllotoxin which is found
in Podophyllum peltatum (May Apple).[1]
Taxus brevifolia
Chemicals extracted from clippings of Taxus brevifolia (Pacific yew) have been used as
the basis for two chemotherapy drugs, docetaxel and paclitaxel.[8]
Euphobia peplus
Contains ingenol mebutate (Picato) which is used to treat skin cancer [9]
Maytenus ovatus
Trastuzumab emtansine (Kadcyla) is an antibody conjugated to a synthetic derivative of
the cytotoxic principle of the Ethiopian plant Maytenus ovatus. It used to treat breast
cancer.

Treatment of cancer:

The goal of cancer treatment is to achieve a cure for your cancer, allowing you to live
a normal life span. This may or may not be possible, depending on your specific
situation. If a cure isn't possible, your treatments may be used to shrink your cancer
or slow the growth of your cancer to allow you to live symptom free for as long as
possible.

Cancer treatments may be used as:

 Primary treatment. The goal of a primary treatment is to completely remove

the cancer from your body or kill all the cancer cells.
 Any cancer treatment can be used as a primary treatment, but the most
common primary cancer treatment for the most common types of cancer is
surgery. If your cancer is particularly sensitive to radiation therapy or
chemotherapy, you may receive one of those therapies as your primary
treatment.

 Adjuvant treatment. The goal of adjuvant therapy is to kill any cancer cells

that may remain after primary treatment in order to reduce the chance that the
cancer will recur.

Any cancer treatment can be used as an adjuvant therapy. Common adjuvant

therapies include chemotherapy, radiation therapy and hormone therapy.

Neoadjuvant therapy is similar, but treatments are used before the primary
treatment in order to make the primary treatment easier or more effective.

 Palliative treatment. Palliative treatments may help relieve side effects of

treatment or signs and symptoms caused by cancer itself. Surgery, radiation,
chemotherapy and hormone therapy can all be used to relieve symptoms. Other
medications may relieve symptoms such as pain and shortness of breath.

Palliative treatment can be used at the same time as other treatments intended
to cure your cancer.

Many cancer treatments are available. Your treatment options will depend on several
factors, such as the type and stage of your cancer, your general health, and your
preferences. Together you and your doctor can weigh the benefits and risks of each
cancer treatment to determine which is best for you.

Cancer treatment options include:

 Surgery. The goal of surgery is to remove the cancer or as much of the

cancer as possible.

 Chemotherapy. Chemotherapy uses drugs to kill cancer cells.

 Radiation therapy. Radiation therapy uses high-powered energy beams,

such as X-rays or protons, to kill cancer cells. Radiation treatment can come
from a machine outside your body (external beam radiation), or it can be placed
inside your body (brachytherapy).
 Bone marrow transplant. Your bone marrow is the material inside your
bones that makes blood cells from blood stem cells. A bone marrow transplant,
also knowns as a stem cell transplant, can use your own bone marrow stem
cells or those from a donor.

A bone marrow transplant allows your doctor to use higher doses of

chemotherapy to treat your cancer. It may also be used to replace diseased
bone marrow.

 Immunotherapy. Immunotherapy, also known as biological therapy, uses

your body's immune system to fight cancer. Cancer can survive unchecked in
your body because your immune system doesn't recognize it as an intruder.
Immunotherapy can help your immune system "see" the cancer and attack it.

 Hormone therapy. Some types of cancer are fueled by your body's

hormones. Examples include breast cancer and prostate cancer. Removing
those hormones from the body or blocking their effects may cause the cancer
cells to stop growing.

 Targeted drug therapy. Targeted drug treatment focuses on specific

abnormalities within cancer cells that allow them to survive.

 Cryoablation. This treatment kills cancer cells with cold. During cryoablation,

a thin, wandlike needle (cryoprobe) is inserted through your skin and directly
into the cancerous tumor. A gas is pumped into the cryoprobe in order to freeze
the tissue. Then the tissue is allowed to thaw. The freezing and thawing
process is repeated several times during the same treatment session in order to
kill the cancer cells.

 Radiofrequency ablation. This treatment uses electrical energy to heat

cancer cells, causing them to die. During radiofrequency ablation, a doctor
guides a thin needle through the skin or through an incision and into the cancer
tissue. High-frequency energy passes through the needle and causes the
surrounding tissue to heat up, killing the nearby cells.

 Clinical trials. Clinical trials are studies to investigate new ways of treating

cancer. Thousands of cancer clinical trials are underway.
 Conclusion:
High‐throughput screening and combinatorial chemistry have not provided the numbers of high ‐quality
leads that were anticipated. In the future success of the pharmaceutical industry depends not only on high‐
throughput screening and combinatorial chemistry, but on the combining of complementary
technologies, such as natural product discovery, genomics, proteomics, metabolomics, metagenomics,
structure‐function drug design, semi‐synthesis, recombinant DNA methodology, genome mining and
combinatorial biosynthesis. Synthetic biology offers exciting technologies for new natural product drug
discovery and the future development of anti‐tumor compounds  . [13]

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