NEW TRENDS IN THE CHEMISTRY OF ANTICANCER DRUGS

www.wjpr.netVol 4, Issue 09, 2015.

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Elserwy. World Journal of Pharmaceutical Research

NEW TRENDS IN THE CHEMISTRY OF ANTICANCER DRUGS

Walaa S. Elserwy*

Therapeutical Chemistry Department, National Research Centre, Dokki, Giza, Egypt.

ABSTRACT

The majority of conventional chemotherapeutic agents cause cell death

by directly inhibiting the synthesis of DNA or interfering with its

function. This means that they are often not tumor-specific and are

associated with considerable morbidity. Nowadays there are many

trends in the chemistry of anticancer drugs appear and there is no doubt

that almost of these trends help each others in order to give good

results in anticancer drugs research. This review aims to provide such

an overview.

KEYWORDS: Cancer, Molecular Docking, Nanotechnology,

Hormonal Therapy.

INTRODUCTION

Cancer is one of the most widespread and feared diseases in the world today, feared largely

because it is known to be difficult to cure. The main reason for this difficulty is that cancer

results from the uncontrolled multiplication of subtly modified normal human cells. Around

the world, tremendous resources are being invested in prevention, diagnosis, and treatment of

cancer. One of the main methods of modern cancer treatment is drug therapy (chemotherapy).

The development of more effective drugs for treating patients with cancer has been a major

human endeavor over the past 50 years, and the 21st century now promises some dramatic

new directions.

Cancer

What is cancer? Cancers are a large family of diseases that involves abnormal cell growth

with the potential to invade or spread to other parts of the body. They form a subset of

neoplasms. A neoplasm or tumor is a group of cells that have undergone unregulated growth,

and will often form a mass or lump.

World Journal of Pharmaceutical Research SJIF Impact Factor 5.990

7105 –2277ISSN Article viewRe. 2132-2109Volume 4, Issue 9,

Article Received on

15 July 2015,

Revised on 06 Aug 2015,

Accepted on 31 Aug 2015

*Correspondence for

Author

Dr. Walaa S. Elserwy

Therapeutical Chemistry

Department, National

Research Centre, Dokki,

Giza, Egypt.

http://www.wjpr.net/



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Fig. 1: Diagram of cells forming a tumour

Cancer Treatments

The treatment given for cancer is highly variable and dependent on the type, location, the

amount of disease and the health status of the patient.

The treatments are designed to either:

Directly kill/remove the cancer cells.

To lead to their eventual death by depriving them of signals needed for cell division.

The treatments work by stimulating the body's own defenses.

Classical types of cancer treatment

Chemotherapy: A term used for a wide array of drugs used to kill cancer cells.

Chemotherapy drugs work by damaging the dividing cancer cells and preventing their

further reproduction.

Surgery: Often the first line of treatment for many solid tumors. If the cancer is detected

at an early stage, surgery may be sufficient to cure the patient.

Radiation: The goal of radiation is to kill the cancer cells directly by damaging them

with high energy beams. The radiation is most commonly low energy x-rays for treating

skin cancers, while higher energy x-ray beams are used in the treatment of cancers within

the body.[1]

Anticancer Drugs

Introduction: It is difficult to assign a date to the beginning of the treatment of cancer with

drugs because herbs and other preparations have been used for cancer treatment since

antiquity. However, the 1890s, a decade that represents an extraordinarily creative period in

painting, music, literature, and technology, encompassed discoveries that were to set the




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scene for developments in cancer treatment in the 20th century. The discovery of penetrating

radiation, or x-rays, by Roentgen in Germany in 1895 was complemented 3 years later by the

discovery of radium by Marie and Pierre Curie. The efficacy of chemotherapy depends on the

type of cancer and the stage. In combination with surgery, chemotherapy has proven useful in

a number of different cancer types including: breast cancer, colorectal cancer, pancreatic

cancer, testicular cancer, ovarian cancer, and certain lung cancers. The overall effectiveness

ranges from being curative for some cancers, such as some leukemias, [2, 3]

to being

ineffective, such as in some brain tumors. [4]

.

Categories of anticancer drugs: Anticancer drugs can be divided into three main categories

based on their mechanism of action.

Fig. 2: Mechanism of action of anticancer drugs

Stop the synthesis of DNA molecule building blocks

These agents work in a number of different ways. DNA building blocks are folic acid,

heterocyclic bases, and nucleotides, which are made naturally within cells. All of these agents

work to block some steps in the formation of nucleotides or deoxyribonucleotides (necessary

for making DNA). When these steps are blocked, the nucleotides, which are the building

blocks of DNA and RNA, can't be synthesized. Thus the cells can't replicate because they

can't make DNA without the nucleotides. Examples of drugs in this class include.

1) Methotrexate (Abitrexate®)

2) Fluorouracil (Adrucil®)

3) Hydroxyurea (Hydrea®)



https://en.wikipedia.org/wiki/Leukemias


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4) Mercaptopurine (Purinethol®)

Directly damage the DNA in the nucleus of the cell

These agents chemically damage DNA and RNA. They disrupt replication of the DNA and

either totally halts replication or cause the manufacture of nonsense DNA or RNA (i.e. the

new DNA or RNA does not code for anything useful). Examples of drugs in this class

include.

1) Cisplatin (Platinol®)

2) Antibiotics - daunorubicin (Cerubidine®)

3) Doxorubicin (Adriamycin®)

4) Etoposide (VePesid®)

Effect the synthesis or breakdown of the mitotic spindles

Mitotic spindles serve as molecular railroads with "North and South Poles" in the cell when a

cell starts to divide itself into two new cells. These spindles are very important because they

help to split the newly copied DNA such that a copy goes to each of the two new cells during

cell division. These drugs disrupt the formation of these spindles and therefore interrupt cell

division. Examples of drugs in this class.

1) Vinblastine (Velban®)

2) Vincristine (Oncovin®)

3) Pacitaxel (Taxol®).

Best Selling Cancer Drugs

Nick Mulcahy wrote in Medscape Medical News (http://www.medscape.com) the best selling

cancer drugs in 2013 according to data compiled by Evaluate Pharma, a pharmaceutical

intelligence company (June 12, 2014).

Table.1: Best selling cancer drugs in 2013.

Drug Sales (in billions) Cancer Indications

Rituxan $7.78 Non-Hodgkin's lymphoma,

chronic lymphocytic leukemia

Avastin $6.75 Colorectal, lung, kidney, and

glioblastoma

Herceptin $6.56 Breast, esophageal, and gastric

Gleevec $4.69 Variety of leukemias and

gastrointestinal stromal tumors

Neulasta $4.39 Febrile neutropenia

Revlimid $4.28 Multiple myeloma, mantle cell

lymphoma, myelodysplastic



http://www.medscape.com/


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syndromes

Alimta $2.70 Lung

Velcade $2.61 Multiple myeloma, mantle cell

lymphoma

Erbitux $1.87 Colorectal, head and neck

Zytiga $1.70 Prostate

Simon King wrote in FirstWord Lists (http://www.firstwordpharma.com) the best selling

cancer drugs in 2014 (May 31st, 2015).

Table.2: Best selling cancer drugs in 2014

1. Rituxan® (Rituximab) The first selling cancer drug in 2013 and 2014, our top contender

is made by Roche Company. Rituxan is primarily found on the surface of immune system B

cells. Based on its safety and effectiveness in clinical trials,[5]

Rituxan was approved by the

U.S. Food and Drug Administration in 1997 to treat B-cell non-Hodgkin lymphomas (NHLs)

resistant to other chemotherapy regimens.[6]

It was the first monoclonal antibody drug,

meaning that the drug was the first oncology drug developed to target a specific protein or

cells, which may then stimulate the body’s immune system to attack those cells. Rituxan is

used to treat cancers of the white blood system such as leukemias and lymphomas, including

non-Hodgkin's lymphoma and lymphocyte predominant subtype of Hodgkin's Lymphoma.[7]



http://www.firstwordpharma.com/

https://en.wikipedia.org/wiki/Leukemia


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2. Avastin® (Bevacizumab) The second selling cancer drug in 2013 and 2014. Another of

Roche’s long standing cancer blockbusters. Avastin is produced in a mammalian (Chinese

Hamster Ovary cell) expression system in a nutrient medium. Avastin, like most of the

medicines on our list, has now been on the market for a decade. The drug, which is known

generically as Bevacizumab, is used primarily to treat colon cancer, has gained several new

expansions in the years since its initial approval in 2003, and is now used to treat lung, breast,

and kidney cancers. Clinical trials are underway to test an intra-arterial technique for

delivering the drug directly to brain tumors, bypassing the blood–brain barrier.[8]

Avastin has

also demonstrated activity in glioblastoma multiforme. [9]

3. Herceptin® (Trastuzumab) The third selling cancer drug in 2013 and 2014. Herceptin,

generically known as Trastuzumab and developed by Genentech (Roche), is one of the most

widely used breast cancer treatments currently on the market. The biotech company

Genentech developed Herceptin jointly with UCLA and gained FDA approval in September

1998.

4. Revlimid® (Lenalidomide)

Fig. 3: Revlimid [Systematic (IUPAC) name: (RS)-3-(4-Amino-1-oxo 1,3-dihydro-2H-

isoindol- 2-yl)piperidine-2,6-dione]

The sixth selling cancer drug in 2013 and the fourth selling cancer drug in 2014. Like several

other drugs on this list, Revlimid is an older medicine, first approved by the FDA in 2006.

Revlimid has significantly improved overall survival in myeloma (which generally carries a

poor prognosis), although toxicity remains an issue for users. [10]

It costs $163,381 per year

for the average patient. [11]

Revlimid is one of the novel drug agents used to treat multiple

myeloma. It is a more potent molecular analog of Thalidomide, which inhibits tumor

angiogenesis and tumor proliferation. [12, 13]

Revlimid synthesized as below. [14]



https://en.wikipedia.org/wiki/Bevacizumab#cite_note-BBB-19

https://en.wikipedia.org/wiki/Glioblastoma_multiforme

https://en.wikipedia.org/wiki/International_Union_of_Pure_and_Applied_Chemistry_nomenclature


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Fig. 4: Revlimid synthesis

5. Gleevec® (Imatinib)

Fig. 5: Gleevec [Systematic (IUPAC) name: 4-[(4-methylpiperazin-1-yl)methyl]-N-(4-

methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}phenyl)benzamide]

The fourth selling cancer drug in 2013 and the fifth selling cancer drug in 2014. Gleevec was

first approved in 2001, often called a ―wonder drug‖ or ―miracle drug". Because the BCR-

Abl tyrosine kinase enzyme exists only in cancer cells and not in healthy cells, Gleevec

works as a form of targeted therapy, only cancer cells are killed through the drug's action. In

this regard, Gleevec was one of the first cancer therapies to show the potential for such

targeted action, and is often cited as a paradigm for research in cancer therapeutics. [15]

A

2012 economic analysis funded by Bristol-Myers Squibb estimated that the discovery and

development of Gleevec and related drugs had created $143 billion in societal value at a cost

to consumers of approximately $14 billion. The $143 billion figure was based on an

estimated 7.5 to 17.5 year survival advantage conferred by Gleevec treatment, and included

the value of ongoing benefits to society after the Gleevec patent expiration. [16]

After the

Philadelphia chromosome mutation and hyperactive BCR-Abl protein was discovered, the

investigators screened chemical libraries to find a drug that would inhibit that protein, they

identified 2-phenylaminopyrimidine. This lead compound was then tested and modified by

the introduction of methyl and benzamide groups to give it enhanced binding properties,

resulting in Gleevec. [17]




https://en.wikipedia.org/wiki/Benzamide


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6. Velcade® (Bortezomib)

Fig. 6: Velcade [Systematic (IUPAC) name: [(1R)-3-methyl-1-({(2S)-3-phenyl-2-

[(pyrazin-2-ylcarbonyl)amino]propanoyl}amino)butyl]boronic acid]

The eighth selling cancer drug in 2013 and the sixth selling cancer drug in 2014. The drug

was approved as a first line treatment for the blood cancer by the UK’s National Institute for

Health and Care. In May 2003, seven years after the initial synthesis, Velcade was approved

in the United States by FDA for use in multiple myeloma. [18]

7. Alimta® (Pemetrexed)

dihydro -1,7-oxo-4-amino-(2-[2-4{[-2-)S) name: (2IUPACSystematic ([ : AlimtaFig. 7

pyrrolo [2,3-d]pyrimidin-5-yl)ethyl]benzoyl]amino} pentanedioic acid]

The seventh selling cancer drug in 2013 and 2014. First developed to treat mesothelioma and

later also approved for the treatment of lung cancer. On September 2008, the FDA granted

approval as a first-line treatment, in combination with Cisplatin, against lung cancer. [19, 20]

8. Zytiga® (Abiraterone)

Fig. 8: Zytiga [Systematic (IUPAC) name: (3β)-17-(pyridin-3-yl)androsta-5,16-dien-3-

ol]

The tenth selling cancer drug in 2013 and the eighth selling cancer drug in 2014. In the early

1990s, Mike Jarman, Elaine Barrie and Gerry Potter of the Cancer Research UK Centre for







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Cancer Therapeutics within the Institute of Cancer Research in London set out to develop

drug treatments for prostate cancer. Zytiga was first approved in 2011.

9. Erbitux® (Cetuximab) The ninth selling cancer drug in 2013 and 2014. Erbitux

developed as part of a partnership between Merck and Bristol-Myers Squibb Company. The

drug, used in the treatment of colon, head, and neck cancers is specialized; however, Merck

has done little to expand the drug to new indications, resulting in a steady drop-off in sales.

Erbitux only works on tumors that are not mutated. [21]

10. Afinitor® (Everolimus)

Fig. 9: Afinitor [Systematic (IUPAC) name: dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-(2-

hydroxyethoxy)-3-methoxycyclohexyl]propan-2-yl]-19,30-dimethoxy-15,17,21,23,29,35-

hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.0 hexatriaconta-16,24,26,28-tetraene-

2,3,10,14, 20-pentone]

The tenth selling cancer drug in 2014 but didn't find in the list of best selling anticancer drugs

in 2013. Afinitor (everolimus) is a cancer medicine that interferes with the growth of cancer

cells and slows their spread in the body.

11. Neulasta® (Pegfilgrastim) The fifth selling cancer drug in 2013 but didn't find in the list

of best selling anticancer drugs in 2014. Neulasta (pegfilgrastim) is a man-made form of a

protein that stimulates the growth of white blood cells in the body. White blood cells help the

body fight against infection.

New Trends In The Chemistry Of Anticancer Drugs

1- Molecular Docking

Introduction: The field of molecular docking has emerged during the last three decades,

driven by the needs of structural molecular biology and structure-based drug discovery. It has

been greatly facilitated by the dramatic growth in the availability and power of computers,

and the growing ease of access to small molecule and protein databases. [22–25]

Docking is a





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method which predicts the preferred orientation of one molecule to a second when bound to

each other to form a stable complex. [26]

Hence docking plays an important role in the rational

design of drugs.[27]

Theory: There are a number of excellent reviews of molecular docking methods [28, 29]

and a

large number of publications comparing the performance of a variety of molecular docking

tools.[30–37]

Fig. 10: A typical docking workflow. This flowchart shows the key steps common to all

docking protocols.

Methods: No matter which docking method is selected, the user needs to prepare the

appropriate input files. This will depend on the docking method used. The number of docking

programs currently available is high and has been steadily increasing over the last decades.

The following list presents an overview of the most common protein-ligand docking

programs, [38]

with indication of the corresponding year of publication and country of origin.

This list is comprehensive but not complete.

Table.3: List of Protein-Ligand Docking Software

Program Country of Origin Year Published

AADS India 2011

ADAM Japan 1994

AutoDock USA 1990

AutoDock Vina USA 2010

BetaDock South Korea 2011

DARWIN USA 2000

DOCK USA 1988

Glide USA 2004

EADock Switzerland 2007

eHiTS UK 2006

EUDOC USA 2001




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FDS UK 2003

ICM-Dock USA 1997

Docking may be useful for comparing drugs with each other in order to know which drug

more active, for example: Ambrish KS.et.al in 2015 studied the molecular docking of

Thalidomide, Lenalidomide (The sixth selling cancer drug in 2013 and the fourth selling

cancer drug in 2014) and Pomalidomide with human activated C-protein, which is

responsible for multiple myeloma and noticed that Pomalidomide binds more efficiently than

Lenalidomide.[39]

Fig. 11: Schematic structures of Thalidomide (a), Lenalidomide (b) and

Pomalidomide (c).

Fig. 12: Representative structure of human activated C-protein (a), docked with

Thalidomide (b), Lenalidomide (c) and Pomalidomide (d). The docking region is

encircled by white color.




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2- Nanotechnology

What is Nanotechnology? Nanotechnology is science, engineering, and

technology conducted at the nanoscale, which is about 1 to 100 nanometers. Nanoscience and

nanotechnology are the study and application of extremely small things and can be used

across all the other science fields, such as chemistry, biology, physics, materials science, and

engineering. One of the most active research areas of nanotechnology is nanomedicine, which

applies nanotechnology to highly specific medical interventions for the prevention, diagnosis

and treatment of diseases. [40, 41]

How it Start? The ideas and concepts behind nanoscience and nanotechnology started with a

talk entitled ―There’s Plenty of Room at the Bottom‖ by physicist Richard Feynman at an

American Physical Society meeting at the California Institute of Technology on December

29, 1959. In his talk, Feynman described a process in which scientists would be able to

manipulate and control individual atoms and molecules. Nanotechnology as defined by size is

naturally very broad, including fields of science as organic chemistry and molecular biology,

etc. [42]

Fig. 13: Richard Feynman (born in May 11, 1918, Queens, New York, United States,

died in February 15, 1988 (aged 69) Los Angeles, California, United States)

Nanocarriers Conventional chemotherapy employs drugs that are known to kill cancer cells

effectively. But these cytotoxic drugs kill healthy cells in addition to tumor cells, leading to

adverse side effects such as nausea, hair-loss and fatigue. Nanoparticles can be used as drug

carriers for chemotherapeutic to deliver medication directly to the tumor while sparing

healthy tissue. Nanocarriers have several advantages over conventional chemotherapy. They

can.




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Protect drugs from being degraded in the body before they reach their target.

Enhance the absorption of drugs into tumors and into the cancerous cells themselves.

Prevent drugs from interacting with normal cells, thus avoiding side effects.

Targeting Strategies Two basic requirements should be realized in the design of nanocarriers

to achieve effective drug delivery (Fig.14). First, drugs should be able to reach the desired

tumor sites. Second, drugs should only kill tumor cells without harmful effects to healthy

tissue. [43]

These requirements may be enabled using two strategies: passive and active

targeting of drugs. [44]

Fig. 14

Passive Targeting Passive targeting takes advantage of the unique pathophysiological

characteristics of tumor vessels, enabling nanodrugs to accumulate in tumor tissues.

Typically, tumor vessels are highly disorganized and dilated with a high number of pores.

The 'leaky' vascularization, which refers to the EPR effect, allows migration of

macromolecules up to 400 nm in diameter into the surrounding tumor region. [44–46]

Active Targeting One way to overcome the limitations of passive targeting is to attach

affinity ligands (antibodies, [47]

peptides, [48]

or small molecules [49]

that only bind to

specific receptors on the cell surface) to the surface of the nanocarriers by a variety of

conjugation chemistries. Nanocarriers will recognize and bind to target cells through

ligand–receptor. In order to achieve high specificity, those receptors should be highly

expressed on tumor cells, but not on normal cells. To fully explore the application of

targeted drug delivery, we need to investigate whether the specific diseases are the correct

application for targeting and whether the properties of the therapeutic drugs, as well as

their site and mode of action, are suited for targeting. [50]

There are many patents on the

clinical use of nanoparticles, for example, Jose P.et.al in 2014 reviewed patents on the




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clinical use of nanoparticles for gastrointestinal cancer diagnosis and therapy and to offer

an overview of the impact of nanotechnology on the management of this disease.[51]

Gold Nanoparticles in (Chemotherapy) A gold nanoparticle in chemotherapy is the use of

gold in therapeutic treatments, often for cancer or arthritis. To increase specificity and

likelihood of drug delivery.

Fig. 15: Gold Nanoparticles

Gold nanorod technology: Gold nanorod technology developed by Mostafa A. El-Sayed lab.

Mostafa A. El-Sayed (born 8 May 1933) is an Egyptian-American chemical physicist, a

leading nanoscience researcher, a member of the National Academy of Sciences and a US

National Medal of Science laureate. A major focus of his lab is currently on the optical and

chemical properties of noble metal nanoparticles and their applications in nanocatalysis,

nanophotonics and nanomedicine. Gold nanoparticles (AuNPs), nanorods, and nanoshells

with unique properties [52-54]

have been shown to be of potential use in anticancer drug

delivery systems and photothermal cancer treatment agents. [55-58]

Fig. 16: Mostafa El-Sayed, born in 8 may 1933, Egypt

Drug Vectorization Nanovectors should contain anticancer drug as core nanoparticles, in

which it can protect normal cells by storing anticancer drugs inside. Research shows that

80~90% of breast cancer tumor cells have estrogen receptors [59]

and 60~70% of prostate



https://en.wikipedia.org/wiki/Nanorod


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cancer tumor cells have androgen receptors.[60]

These significant amounts of hormone

receptors play a role in intermolecular actions. This role is now used by targeting and

therapeutic ligands on gold nanoparticles to target tissue-selective anti-tumor drug delivery.

In order to have multiple targeting and therapeutic ligands bind with gold nanoparticles, the

gold nanoparticles has undergo polymer stabilization. For example, anti-estrogen molecules

with thiolated PEG bind with gold nanoparticles via Au-S bonds, this process forms thiolate

protected gold nanoparticles. [61]

For example: In 2009 Mostafa A. El-Sayed et.al synthesized

Tamoxifen-poly (ethylene glycol)-thiol gold nanoparticle conjugates and approved that they

enhanced potency and selective delivery for breast cancer treatment. [62]

Fig. 17: Synthesis of Thiol-PEGylated Tamoxifen (TAM-PEG-SH) (a) and Covalent

Attachment to 25 nm Gold Nanoparticles (AuNPs) (b)

3-Hormonal Therapy

What hormones are? Hormones are natural substances made by glands in our bodies. The

network of glands that make hormones is called the endocrine system. Hormones are carried

in our bloodstream and act as messengers between one part of our body and another. They

have lots of effects and one of these is controlling the growth and activity of certain cells and

organs.

What hormone therapy is? Some cancers use these hormones to grow. Hormone therapy for

cancer is the use of medicines to block the effects of hormones. It does not work for all types

of cancer. Doctors use hormone therapy for people with cancers that are hormone sensitive or

hormone dependent.




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Types of hormone therapy: There are a number of different types of hormone therapy, for

example.

Adrenal steroid inhibitors: This type of hormone therapy interferes with the hormones

produced by the adrenal gland. The adrenal glands are located on top of the kidneys. The

outer portion of the adrenal gland (the adrenal cortex) produces hormones called

corticosteroids. When these corticosteroids are blocked from being made, they are not able to

signal the body to produce other hormones such as estrogen and androgens. The resulting

decrease of estrogens and androgens interferes with the stimulation of cancer growth in

tumors that are influenced by these hormones. For example of adrenal steroid inhibitors.

Aminoglutethimide, Mitotane

Fig. 18: a) Aminoglutethimide, b) Mitotane

Androgens: are hormones such as testosterone and androsterone that produce or stimulate

the development of male characteristics. In women, these hormones can be converted

into estrogen. Androgens as cancer therapy are used to oppose the activity of estrogen,

thereby slowing the growth of cancer. For example of androgens.

Fluoxymesterone, Testosterone, Testolactone

Fig. 19: a) Fluoxymesterone, b) Testosterone, c) Testolactone




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Antiestrogens: bind to estrogen receptor site on cancer cells thus blocking estrogen from

going into the cancer cell. This interferes with cell growth and eventually leads to cell

death. For example of antiestrogens.

Tamoxifen, Toremifene

Fig. 20: a) Tamoxifen, b) Toremifene

4-Photodynamic Therapy (PDT)

Fig. 21: Close up of surgeons' hands in an operating room with a beam of light traveling

along fiber optics for photodynamic therapy. Its source is a laser beam which is split at

two different stages to create the proper therapeutic wavelength. A patient is given a

photosensitive drug that is absorbed by cancer cells. During the surgery, the light beam

is positioned at the tumor site, which then activates the drug that kills the cancer cells,

thus photodynamic therapy (PDT).

What photodynamic therapy is? Photodynamic therapy (PDT), sometimes called

photochemotherapy, is a form of phototherapy using nontoxic light-sensitive compounds that

are exposed selectively to light, whereupon they become toxic to targeted malignant and

other diseased cells. PDT is used clinically to treat a wide range of medical conditions, such

as malignant cancers. [63]




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History While the applicability and potential of PDT has been known for over a hundred

years,[64]

the development of modern PDT has been a gradual one, involving scientific

progress in the fields of photobiology and cancer biology, as well as the development of

modern photonic devices, such as lasers and LEDs.[65]

It was John Toth as product manager

for Cooper Medical Devices Corp/Cooper Lasersonics who acknowledged the

"photodynamic chemical effect" of the therapy and wrote the first "white paper" branding the

therapy as "Photodynamic Therapy" (PDT).

How PDT works When the sensitizing drugs are exposed to their particular light, they

produce a type of oxygen that kills nearby cells. PDT directly kills cancer cells. The

sensitizing drug may damage blood vessels in the tumor, and stop it from receiving nutrients

that it needs. PDT may also trigger the immune system to attack the cancer cells. in order to

achieve the selective destruction of the target area using PDT while leaving normal tissues

untouched, either the photosensitizer can be applied locally to the target area. For instance, in

the treatment of skin conditions, including acne, psoriasis, and also skin cancers, the

photosensitizer can be applied locally excited by a light source. In the local treatment of

internal tissues and cancers, after photosensitizers have been administered intravenously,

light can be delivered to the target area using endoscopes and fiber optic catheters.

PDT drugs approved in the US to treat cancer Several photosensitizing agents are currently

approved by the US Food and Drug Administration (FDA) to treat certain cancers. For

example.

Porfimer sodium (Photofrin®)

Porfimer sodium is the most widely used and studied photosensitizer. It’s activated by red

light from a laser. It accumulates in malignant tissue and is activated by laser light to produce

a cytotoxic effect. It is given for obstructing oesophageal cancer and non-small cell lung

cancer. The main complications are oesophagitis and photo-reactions [66]

. In one case, a 75-

year-old man with emphysema and a tumor of the right intermediate bronchus had four

months' treatment and the tumor disappeared with no recurrence for three years. It is safe for

patients with poor pulmonary function. [67]




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Fig. 22: Porfimer sodium

CONCLUSION

Cancer is one of the most widespread and feared diseases in the world today, feared largely

because it is known to be difficult to cure. The main reason for this difficulty is that cancer

results from the uncontrolled multiplication of subtly modified normal human cells. Around

the world, tremendous resources are being invested in prevention, diagnosis, and treatment of

cancer. One of the main methods of modern cancer treatment is drug therapy (chemotherapy).

Nowadays there are many trends in the chemistry of anticancer drugs.

ACKNOWLEDGMENTS

The authors would like to thank National Research Centre, Therapeutical Chemistry

Department, Dokki, Giza, Egypt for providing all the facilities for the research.

Conflict of interest No conflict of interest is there to declare.

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