Chemotherapy

Chemotherapy is the use of medications aimed to kill those actively dividing cells. It is used to control or destruct cancer or prevent recurrence of the disease. Chemotherapy works to treat the disease throughout the body and is supposed to relieve symptoms and extend the life of the patient.

Chemistry plays a crucial role in drug development for cancer treatment methods. Chemists have to identify the chemical compounds that exhibit anticancer activity. Having used some techniques, such as distillation and chromatographic separation, scientists can isolate, purify and determine the structure of natural products considered pharmaceuticals. Chemistry is used to determine the structure-activity relationship, defined as the relationship between the chemical structure of a molecule and its biological or pharmacological activity (Shields). Working on treating cancer, chemists have to study the complicated kinetics of chemical compounds within the body, paying attention to the positive and negative changes of physiology caused by a drug.

 

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Chemotherapy drug groups are based on factors depending on their chemical structure and their relationship to another drug and are classified as reactive or interactive. In the first case, the chemical reaction of the drug with a target molecule determines the level of biological activity of the latter. The chemical interferes with the regular cellular processes and, consequently, causes cell death. Such reactive molecules may result in the powerful side effects. If biological activity depends only on the drug's structure, we are dealing with the interactive drugs.

The most effective reactive drugs react slowly to get to their targets and quickly enough to impair the cells before they are rectified. Such strategy can be shown on the example of a platinum drug cisplatin. The +2 oxidation state of the platinum atom of cisplatin builds four coordinated chains in a square projection. Chloride anions deliver two electrons and one negative charge that neutralize the molecule, while ammine supplies two electrons from the filled orbital of nitrogen. As a result, a molecule can cross cell membranes and remains stable to nucleophilic attack. The chlorides start leaving the platinum slowly. Then the molecules of water replace them, thus, being independently and doubly charged. These build-ups are abridged inside the cell, since they cannot penetrate into the cell membrane. Leaving group made of water results in quick reactions with intracellular nucleophiles. The cross-linking of protein and DNA appears readily while being attacked from two sides.

Interactive drugs have the affinity to block normal molecules from binding, thus, reaching the targets before they are decomposed. “Many of these have been extracted from fungi, bacteria, and plants”.

Most anticancer agents appear to have their primary effect on either macromolecular synthesis or function. It means that “they interfere with the DNA (deoxyribonucleic acid), RNA (ribonucleic acid) or proteins or with the appropriate functioning of the preformed molecule”. Thus, alkylating agents interact with the DNA, antibiotics serve as anti-infective substances and antimetabolites/ inhibitors interfere with normal biochemistry; hormones deal with receptors on tumor cells and cytokines regulate the balance of the intercellular communication system. More detailed review of anti-cancer chemicals will help to understand their function.

The chemicals which can prevent cancer cells from reproducing through direct DNA damage belong to Alkylating agents group. Alkylating agents may include different classes of chemicals, such as nitrogen mustards, nitrosoureas, alkyl sulfonates, triazines, and ethylenimines. As a class of drug, these agents work in all phases of the cell cycle. The platinum drugs (cisplatin, carboplatin) relate to alkylating agents since they kill cells in a similar way. Antimetabolites are the group of medicines which interfere with DNA and RNA and work when the cells are dividing at the phase of genetic information copying. The reactions caused with antimetabolites deactivate an enzyme action or replace nucleic acids in DNA and RNA with analogues that retard cells’ replication or repair. Antitumor antibiotics are made of micro-organisms. Examples of these drugs are Bleomycin, Doxorubicin, Mitoxantrone and Daunorubicin.

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In addition, there are drugs that treat cancer, but are not considered as chemotherapy. The drugs, which are made from natural products, refer to the group of Plant alkaloids. Hormonal agents, such ascorticosteroid hormones and sex hormones, help to reduce swelling around tumors of the spinal cord and the brain or control the growth of tumor.

Oncologists recommend a combination of drugs for cancer treatment. Chemotherapy should be given at high enough levels to cure or control the cancer. However, the side effects must be kept at a minimum.