انزيمات 5 Chemotherapy Drugs Drug is a substance used in the diagnosis, treatment, or prevention of a disease or as a component of a medication, they are essentially poisons a small amount wakes you, and any substance intended for use in the diagnosis, cure, treatment, or prevention of disease in humans or other animals is called Drug. Figure(1a) shows simplest structure & large molecules – proteins, molecular weight about 70 kDa, in a human protein structure of tissue plasminogen activator (t-PA; Figure1b). (a) (b) (c) Types of Drugs:- Drugs have two types:- 1- Agonist Drugs (activator) An agonist is a chemical that binds to a receptor and activates the receptor to produce a biological response. Whereas an agonist causes an action, an antagonist blocks the action of the agonist. 2-Antagonist Drugs (inhibitor) They are sometimes called blockers; examples include alpha blockers, beta blockers, with a specific molecule in the biologic system that plays a regulatory role. The target molecule is called a receptor. Drugs interact with receptors by means of chemical forces or bonds. These are of three major types: covalent, electrostatic, and hydrophobic. Example of highly reactive, covalent bond-forming drugs are the DNA- alkylating agents used in cancer chemotherapy to disrupt cell division in the tumor. محاضرة الانزيمات 5 Figure(1) a: Lithium is a practically very important drug in psychiatry, with a molecular weight 6 Da. b:Tissue plasminogen activator is a protein that is recombinantly isolated and used to dissolve blot clots. t-PA is now the ‘gold standard’ in the thrombolytic therapy of brain and myocardial infarctions. The molecular weight of t-PA is about 70 kDa. C:indicate the structure of Aspirin as pain relief drug.

Figure (2):The effect of Aspirin as a pain relief. Covalent bonds are very strong and in many cases not reversible under biologic conditions. For Aspirin is used for inflammation, pain, fever, and blood thinner. The covalent bond formed between Aspirin and an enzyme called cyclooxygenase or (COX) casing deactivation of this enzyme. Cyclooxygenase or (COX) is a key enzyme involved at inflammation and activate the formation of blood clotting (by platelets and red blood cells in blood stream after injury), or stimulate the hypothalamus to increase body Temperature. Inactivation of this enzyme case a pain relief or decrease the body Temperature figure (2). About 2.5 million people/ Year are used Aspirin. Aspirin has disappeared from the bloodstream (after about 15 minutes). Figure (2):The effect of Aspirin as a pain relief. Chemotherapy Chemotherapy:- is the use of any drug to treat any disease. But to most people, the word chemotherapy means drugs used for cancer treatment. It’s often shortened to “chemo.” Chemotherapy is used of chemicals (Drugs) to destroy infectious microorganisms and cancerous cells without damaging the host’s cells. These chemicals function by inhibiting certain cellular enzyme reactions, a highly reactive, covalent bond-forming drugs are the DNA- alkylating agents used in cancer chemotherapy to disrupt cell division in the tumor. Chemotherapeutic agents are divided into:- 1- Antimetabolites. 2- Antibiotics.

Methotrexate Mechanism:- Chemotherapy ANTIMETABOLITES 1-ANTIMETABOLITES: Are chemicals that have structure closely related to that of the substrates of the enzymes act on, thus inhibiting enzymes activity. The presence of antimetabolites can have toxic effects on cells, such as damage cell growth and cell division, so these compounds are used as chemotherapy for cancer. Antimetabolite Drug: Methotrexate, Its a folic acid analog (antifolates that interfere with the use of folic acid). Folic acid is known to prevent certain birth defects(it's important during early stages when baby's brain and spinal cord are being developed, and women who consumed more folic acid had a significant reduced risk of developing high blood pressure, also Folic acid is essential for the production, repair and functioning of DNA, our genetic map and a basic building block of cells. So getting enough folic acid is particularly important. Methotrexate Mechanism:- Mechanism of action: Inhibits dihydrofolate reductase enzyme (DHFR) by binding with high affinity to the active catalytic site of dihydrofolate reductase (DHFR) this inhibit the metabolic processes thereby interferes with the formation of DNA, RNA, and cellular proteins( disturp DNA production of cancer cells). Clinical Applications: Breast cancer, head and neck cancer , primary central nervous system lymphoma, bladder cancer. Toxicity: Mucositis, diarrhea.

ANTIBIOTICS Chemotherapy 2- ANTIBIOTICS: Are compounds produced by one microorganism that are toxic to another Microorganism Figure (3). Their function by inhibiting enzymes that are essential to bacterial growth. Among the most commonly used antibiotics are Penicillin and Tetracycline. Figure (3):The effect of toxic microorganism (Prokaryote) to another Microorganism (Eukaryote). Drug : PENICILLIN It’s a bactericidal antibiotic for (Gram positive+, and Gram negative - bacteria), penicillins inhibit bacterial cell wall synthesis. All penicillin have the basic structure consist of thiazolidine ring & β-lactam ring, shown in Figure(4) below . A thiazolidine ring is attached to a β-lactam ring that carries a secondary amino group, the substituents can be attached to the amino group. Penicillin prevent the bacterial cell wall formation. β-Lactam antibiotics inhibit the formation of peptidoglycan cross-links in the bacterial cell wall, this is achieved through binding of the four-membered β-lactam ring of penicillin to the enzyme DD-Transpeptidase. As a consequence, DD-Transpeptidase cannot catalyze formation of the cross-links of cell wall, and an imbalance between cell wall production and degradation develops, causing the cell to rapidly die. Figure(4):The effect of Penicillin on bacterial cell wall production. Penicillin

How Is Chemotherapy Used to Treat Cancer? Surgery and radiation therapy remove, kill, or damage cancer cells in a certain area, but chemo can work throughout the whole body. This means chemo can kill cancer cells that have spread (metastasized) to parts of the body far away from the original (primary) tumor. Goals of chemotherapy treatment There are three main goals for chemotherapy (chemo) in cancer treatment: 1- Cure If possible, chemo is used to cure cancer, meaning that the cancer is destroyed – it goes away and doesn’t come back. Most doctors don’t use the word “cure” except as a possibility or intention. 2- Control If cure is not possible, the goal may be to control the disease. Chemo is used to shrink tumors and/or stop the cancer from growing and spreading. This can help the person with cancer feel better and live longer. 3- Palliation Chemo can also be used to ease symptoms caused by the cancer. When the cancer is at an advanced stage, meaning it’s not under control. For instance, chemo may be used to help shrink a tumor that’s causing pain or pressure.