IntroductionCancer is a disease characterised by abnormal and uncontrolled cell division attacking the surrounding tissues and organs, and also the distant body parts by circulating with blood and lymph. Cancer is classified into the following categories:1) Carcinoma: This type of cancer starts in the skin or tissues lining the internal organs. There are many sub-types of carcinoma, likeadenocarcinoma,basal cell carcinoma, squamous cell carcinoma, andtransitional cellcarcinoma.2) Sarcoma: This type of cancer starts in the bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissues.3) Leukaemia: This type of cancer starts in the blood -forming tissues (i.e., the bone marrow) and produces numerous abnormal blood cells.4) Lymphoma and Myeloma: This type of cancer starts in the cells of immune system.5) Central Nervous System Cancers: This type of cancer starts in the brain and spinal cord tissues.Antineoplastic or anticancer drugs are used for treating malignancies or cancerous growths. Either these drugs are used alone (chemotherapy) or in combination with surgery or radiation therapy.3.1.2. ClassificationThe anti-neoplastic agents are classified as follows:1) Alkylating agentsNitrogen mustards Mechlorethamine (Mustine HCl) , Ifosfamide, Cyclophosphamide, Chlorambucil, and MelphalanEthylenimine ThiotepaAlkyl sulfonate BusulfanNitrosoureas Carmustine (BCNU) and Lomustine (CCNU)Triazine Dacarbazine (DTIC)2) AntimetabolitesFolate antagonist Methotrexate (Mtx)Purine antagonist 6-Mercaptopurine (6 -MP), 6-Thioguanine (6 -TG), and AzathioprinePyrimidine antagonist5-Fluorouracil (5 -FU) and Cytarabine (cytosine arabinoside)
Certain drugs effectively kill the cycling cells during specific cell cycle phases;these drugs are called phase-specific drugs (figure 3.1). Some other drugs like alkylating agents, are cytotoxic towards the cycling cells in the cell cycle ; these drugs are called cycle-specific drugs.3.1.4. Recent Developments The current strategies for drug development involve drugs with novel modes of action, monoclonal antibodies directed against specific cellular targets, drugs modulating or reversing drug resistance, and drugs used for providing supportive care to the cancer patients. Simple and effective antiemetic therapy and hematopoietic growth factors are the s upportive therapies due to which the administration and management of chemotherapy has become safer and easier.The goals of traditional chemotherapy were limited to ease the symptoms only. Increasing the cytotoxic chemotherapy resulted in significant tumour regression and also improved the control of cancer. The development and acce ptance of combination chemotherapy improved the outcome for incurable neoplastic diseases. This newer approach to cancer treatment included the theoretical point that targeting multiple biochemical processes produces a greater overall effect on tumour regression and remission. The chemotherapy goals shifted to a curative approach for cancers that showed complete responses to chemotherapy. Table 3.1: Chemotherapy Sensitive TumoursRelative Chemosensitivity and Expected Survival OutcomeTypes of Cancer1) Highly Sensitive: Normal survival, possible cure Acute leukaemia in children , Hodgkin’s disease, Diffuse large cell lymphoma, Burkitt’s lymphoma, Wilms’ tumo ur, Testicular carcinoma, Embryonal carcinoma, Ewing’s sarcoma, and Skin cancer.2) Moderately Sensit ive: Increase in survivalOvarian carcinoma, Breast carcinoma, Endometrial carcinoma, Acute leukaemia in adults, Small cell lung cancer, Prostate cancer, Stomach cancer, Cervical cancer, and Neuroblastoma.3) Minimally Sensitive: Someincrease in survival Head and neck cancers, Gastrointestinal cancers, Endocrine gland tumours, Malignant melanoma, Osteogenic sarcoma, and Soft tissue sarcoma.4) Marginally Sensitive: No documented increase in survival Bladder cancer, Oesophageal cancer, Non -small cell lung cancer, Pancreatic carcinoma, and Hepatocellular carcinoma. 3.2. ALKYLATING AGENTS3.2.1. IntroductionAlkylating agents exert cytotoxic and radiomimetic actions. Many of these agents act on dividing and resting cells, and thus are cell cycle -non-specific. Some o f these agents show CNS stimulant and cholinergic properties. Alkylating agents are chemically reactive compounds. It combines most easily with nucleophilic centres, and a fully saturated carbon atom of the alkylating group attaches to the nucleophile.
Subject:- Medicinal chemistry 2
Semester:- Sem 5
Course:- Bachelor of pharmacy