Alkylation agents as Chemotherapeutic agents

Chemotherapy simply agency the use of chemicals to look at disease by destroying microorganism or cancerous or tumour cubiclephones. Gener eithery, chemotherapy acts by destroying rapidly dividing cells although the instrument that leads to this differs. Several divisions of chemotherapy agents exist such as the anti-metabolites, plant alkaloids the topoisomerase inhibitors, anthracyclines and alkylation agents which be discussed in this paper. Generally, alkylation agents tame by addition of alkyl mathematical sorts to the grand of deoxyribonucleic acid molecule at deem 7 atom of imidazole mathematical group (Siddik, 2002).Alkylation agents significance The adduce originates from their ability to alkylate several nuclophilic functional categories in certain cellular conditions . Ex international vitamin Aereles of alkylation agents be carboplatin, oxaliplatin and cisplatin that give out by covalent bond administration with circumstantial carboxyl, sulphurhydril and phosphate groups in molecules of biologic importance (Siddik, 2002). These ar regarded as atomic number 78- found alkylation agents. These platinum fannyd alkylation agent be shared into origin, second and third generations made up of cisplatin,caboplatin and oxaliplatin respectively.They found important use in treatment of mesothelioma . They work at all stage of cell cycle and deflower cellular deoxyribonucleic acid synthesis as rise as transcption (Siddik, 2002). Cisplatin is apply to treat lung and testicular cancers. Other alkylation agents imply chlorambucil, mechlorethamine, ifosfamide and cyclophosphamide as well as procarbazine and bulsulphan. Alkylation agents are sound at all stage of cell cycle devising them useful in treating wide range of cancer particularly the slow growing ones uniform unfluctuating tumor and leukemia (Pizzo &type A Poplack, 2006)All share biochemical mechanism although they may differ in their clinical effects. The significance of alkylation agents is not further seen in treatment of leukemia, lymphomas and solid tumors. They are also found significant in the treatment of non neoplastic conditions such as cyclophosphamide use in treatment of autoimmune disease . Pulse dose cyclophosphamide is used in lupus nephritis and other conditions like Wegeners granulomatosis, multiple sclerosis and unhealthy arthritis (Siddik, 2002).They are not however thaw of side effects especially by and by prolonged use and these let in amenorrhea (cessation of menses), oligospermia (reduction in sperm count) as well as secondary cancers such as acute myelogenous leukemia (Pizzo & Poplack, 2006). General smorgasbord of alkylating chemotherapeutical agents ? Non-specifically acting agents They crosslink yard nucleobases display in double helix of DNA and by so doing stop tumor proliferation. ? Agents that need activation This includes cyclophosphamide which needs in-vovo revolution to active product? Biakylating and Mon oakylating agents The biakylating agents are subject of reacting with two 7-N guanine symmetricalnesss. When these residues are in different DNA strands, there is resulting crosslinkage of DNA strands and this makes DNA double helix to fall in to uncoil (Siddik, 2002). However, when the two guanine moieties are in same base strands, what occurs is cognise as limpet association of DNA to the do drugs molecule. Example of biakylating agent is Bulsuphan . On the contrary, monoakylating agents are only capable of reacting with one 7-N of guanine molecule.? Classical alkylation agents These are termed alkyl groups and they include three subgroups which are (a) the northward chinese mustard greenss which include mephalan, ifosfamide, uramustine, chlorambucil, mechlorethamine and cyclophosphamide b) The nitrosoureas which are carmustine, streptozocin and lomustine c) the alkyl sulphonates such as bulsuphan. ? Alkylation-like agents They lack alkyl group entirely destroy DNA. They are regarded as alkylation-like as they coordinate to DNA so as to interrupt DNA repair permanently.They are the platinum based drugs such as cisplatin,oxaliplatin and carboplatin. They also bind at N7 role of guanine (Siddik, 2002) ? The Non-classical Certain categories are termed non-classical such as altremine and procarbazine. Furthermore, sometimes the platinum based drugs are also regarded as non-classical. northward Mustards The atomic number 7 mustards are a group of DNA alkylation agents which are not specific . They are cytotoxic and have connatural qualities to mustard gas, hence utilized as medicinal and chemical warfare agents.Nitrogen mustards stockpiled by many countries in WW II go as potent and useful tumesce agents. Nitrogen mustards suppress bone amount production of red blood cells. The first nitrogen mustard developed was mustine with anti-neoplastic chemotherapeutic value. Other examples of alkylation agents in nitrogen mustard family are mephalan, cholambu cil, cyclophosphamide, uramustine and ifosfomide (Siddik, 2002). The likes of Bis (2-chloroethyl) ethylamine and Tris (2-choloroethlamine) are few nitrogen mustards used in chemical warfare.Nitrogen mustards mode of action involves governing body of aziridinium or cyclic aminium ion when the amine nitrogen displaces chloride at intermolecular level. This is then followed by alkylation of DNA centers by the azidirium group (Siddik, 2002). break of alkylation DNA is usual during replication (Pizzo & Poplack, 2006). They prevent cell division and by so doing cause abnormal base pairing. Also it is possible that more than a single alkylation groups may exist in each molecule .In order words, these therapeutically useful alkylation agents are either bialkylating or polyalkylating agents (Siddik, 2002). The damaging effect is comparable to that which is seen with vulnerability of genetic material to radiation making it radiometric. Earlier, nitrogen mustards have been shown to form interstrand crosslinks (ICLs) and this administration takes place between N-7 of guanine residue in a 5&8242-d (GC) sequence, although it was later on discovered that nitrogen mustards form a 1,3 Interstrand crosslinks in the 5&8242-d (GNC) sequence (Siddik, 2002).For instance, cyclophosphamide (cytophosphane), a nitrogen mustard arise from oxazophorine group and exhibits their chemotherapeutic effects by its nitrogen mustard metabolite,phosphoramide which form both interstrand and intrastrand crosslinkages at N-7 position of guanine molecule causing cell death. Cyclophosphamide metabolite is usually produced in cell with low amount of ALDH. References Pizzo, P. A & Poplack, D. G. (2006). Principles and practice of pediatric oncology. Lippincott Williams & Wilkins.pp. 310-320. Siddik, Z. H (2002)Mechanism of action of Cancer chemotherapeutic agents DNA-Interactive alkylation agents and antitumour platinum based Drugs. 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