Synthetic Anticancer Drug Useful Against Ovarian Cancer

7/29/2019 Synthetic Anticancer Drug Useful Against Ovarian Cancer

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SYNTHETIC ANTICANCER DRUGS

USEFUL AGAINST OVARIAN CANCER

Submitted by: Faiz Miran

Submitted to:


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AN OVERVIEW

Ovarian cancer, a condition characterized by an overgrowth of malignant cells in one or both of

the ovaries, is one of the deadliest and under-recognized cancers affecting women. Ovarian

cancer is diagnosed in nearly a quarter of a million women globally each year. It is the eighth

most common cancer in women and the seventh leading cause of cancer death among women,

responsible for approximately 140,000 deaths each year. It has the highest mortality rate of all

gynecological cancers. The prognosis for ovarian cancer patients is poor, particularly when the

disease is diagnosed in its later stages. Symptoms are ambiguous and often misdiagnosed, so the

majority of patients are only identified in the advanced stages of the disease. Ovarian cancer is

therefore often referred to as The Silent Killer.

The current standard of care for ovarian cancer - surgery and chemotherapy has

remained unchanged for many years and the 5-year survival rate has improved by only 9% since

1975. Statistics show that just 45% of women with ovarian cancer are likely to survive for five

years compared to up to 89% of women with breast cancer. This outcome is due, in large part, to

the lack of effective prevention and early detection strategies; when diagnosed at an early stage,

the survival rate is approximately 95% with current treatment modalities. Thus, prevention and

early detection of this disease would be of clear clinical benefit

OVARIAN CANCER TREATMENT

When symptoms finally show up and the doctor suspects that a patient may have ovarian cancer,

laparoscopy is conducted to confirm diagnosis. It is a direct visual examination of the abdominal

cavity, the ovaries, the exterior of the fallopian tubes and the uterus using an instrument that is

inserted just underneath the navel. Upon confirmation of ovarian cancer, the doctor explores the

extent of the cancer and submits the patient for surgery. The surgeon removes the growth or


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much of the malignant tissue. In most cases, the whole ovary or both of the ovaries and the

fallopian tubes are removed as they the malignant cancer cells have already affected these areas.

This kind of surgery is called salpingooophorectomy. If the malignant cells affect the uterus,

hysterectomy is conducted (surgical removal of the uterus). Surgery is usually ensued by

radiotherapy, which is the use of high energy radiation to destroy malignant cancer cells in the

body and shrink remaining tumors, which may later on become malignant. This procedure may

be done using an external machine or a radioactive material put inside the body near the

malignant cells.

The patient also undergoes chemotherapy, whereby the patient is given anti-cancer drugs to help

hasten up ovarian cancer treatment. Drugs may be administered orally (through the mouth),

intravenously (through the veins) or through the muscles (by means of injection of a needle.

Most anticancer drugs given to the patient have chemical compounds that are toxic to the

malignant cells; thus, growth of the cancer cells is reduced or stopped. These anticancer drugs

are called cytotoxic drugs. Other anticancer drugs used are synthetic forms of sex hormones such

as androgen drugs and progesterone drugs. In most instances, different kinds of anticancer drugs

are prescribed in combination in order to speed up ovarian cancer treatment. However, not all

ovarian cancer patients are given with the same anticancer drugs. The drugs given to a patient

depends on the extent or stage of development of the ovarian cancer and her general health

condition.

SYENTHETIC ANTICANCER DRUGS USES FOR OVARIAN CANCER

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

treatment of ovarian cancer. Identification of cytotoxic compounds led the development of


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ovarian anticancer therapeutics for several decades. Advances in cancer treatment, however,

continued to be limited by the identification of unique biochemical aspects of malignancies that

could be exploited to selectively target tumor cells. Schwartzman et al. noted in 1988 that of over

600,000 compounds screened by then, less than 40 agents were routinely used in the clinic. The

recent growth in molecular sciences and the advances in genomics and proteomics have

generated several potential new drug targets, leading to changes in the paradigms of anticancer

drug discovery toward synthetic molecularly targeted therapeutics. These shifting paradigms

have not only resulted in the greater involvement of biological scientists in the drug discovery

process but also required changes in the screening and clinical evaluation of drug candidates.

Both small and large synthetic molecular compounds continue to be investigated as anticancer

agents.

Although cytotoxic strategy has achieved significant success, the recent developments in

molecular biology and an understanding of the pharmacology of cancer at a molecular level have

challenged researchers to come up with target-based drugs. These are the agents that are pre-

designed to inhibit and/or modify a selected molecular marker deemed important in cancer

prognosis, growth, and/ or metastasis. Several target-based synthetic compounds have emerged

in recent years. Camptothecin, an alkaloid from the Chinese tree, Camptotheca acuminata

Descne , was discovered by Wall and Wani. Although showing promising antitumor activity,

clinical studies were discontinued due to unpredictable side effects. Subsequent semisynthetic

modifications led to the development of Ironotecan (Topotecin, Campto), a derivative of

camptothecin that is now clinically available. The camptothecins act by inhibition of the

topoisomerase I.


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N

N

O

OH

Camptothecin

N

N

O

OH

N

N

N

O

O

Ironotecan

Included among the most important anticancer drugs in use today are tamoxifen and

methotrexate, which are both synthetic drugs for ovarian cancer. Tamoxifen was derived from

the diethylstilbesterol nucleus, which itself was patterned after estradiol. First reported for its

contraceptive activity in rats, tamoxifen was later found to bind to human estrogen receptors,

thus paving the way for its use in the treatment of breast cancer. Tamoxifen is now one of the

most widely used and successful drugs in the treatment of ovarian cancer. Methotrexate is an

antifolate, patterned after physiological folate, is one of the most widely used antineoplastic

drugs available, and shows efficacy in the treatment of a variety of neoplasms.

O

O

O


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ON

CH3

CH3CH3

Tamoxifen

Methotrexate

Although most of the drugs in use today are synthetic drugs, many (perhaps half or more) had

their beginnings as natural products. Only a few have been cited here for illustrative purposes.

Safety, efficacy, pharmacokinetics, metabolic or chemical stability, and other important

characteristics of a drug are functions of the chemical structure of the molecule, not its origin.

The molecular structure of a compound, which defines its interactions with other molecules in

the body, is the prime reason it exhibits desirable and/or undesirable biological activities.

Whether the compound is of natural or synthetic origin is irrelevant. To correlate origin with an

expected greater or lesser safety profile or desirable features is unfounded, and can be

dangerously misleading. Many of the most toxic chemical substances known are natural

products, and some of the safest, most effective, and widely used drugs are of synthetic origin. In

fact, structureactivity relationship (SAR) studies and synthetic modifications of bioactive

N

N N

N

NH2

NH2

N

CH3

CONHCH(CO2H)CH2CH2CO2H


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natural products are usually done in an effort to produce an improved drug substance with a

better therapeutic index. Thus, many of the most successful and important drug substances are

derived through a combination of natural product chemistry and synthetic chemistry.

Synthetic Anticancer Drug Useful Against Ovarian Cancer

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