Sources of Drugs : Natural and modern sources

Sources of drugs

Sources of drugs

Throughout history, new drug discovery has enabled human well-being and advancement, not only by ensuring survival in the wake of infections and debilitating diseases but also by steadily advancing the quality of life. For example, the discovery of penicillin by Alexander Fleming in 1928 saved countless lives and paved the way for the antibiotic medicines. More recent examples of life-saving medicines include the discovery and commercialization of statins for the management of hypercholesterolemia and humanized monoclonal antibodies targeting the immune checkpoints for the immunotherapy of cancer.

Identification of new molecules with the potential to produce a desired therapeutic effect involves a combination of (1) molecular physiology and pathophysiology; that is, research on the molecular mechanisms of biological process and disease progression; (2) review of known therapeutic agents; and/or (3) conceptualization and synthesis/procurement of potential new molecules that may also involve random selection and broad biological screening.

Plant sources

Natural compounds extracted from plants have often provided novel structures for therapeutic applications. For example, vincristine is derived from the periwinkle plant Vinca rosea, etoposide is from the mandrake plant Podophyllum peltatum

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, taxol is from the pacific yew Taxus brevifolia, doxorubicin is a fermentation product of the bacteria Streptomyces, l-asparaginase is from Escherichia coli or E. cartovora, rhizoxin is from the fungus Rhizopus chinensis, cytarabine is from the marine sponge Cryptotethya crypta, and bryostatin is from the sea moss Bugula neritina.

Another example is paclitaxel (Taxol®), prepared from the extract of the pacific yew, used in the treatment of ovarian cancer. Digoxin is one of the most widely used drugs in the management of congestive heart failure, weakened heart, and irregular heart beat (arrhythmia). The common garden plant, the foxglove or Digitalis purpurea , is the source of digoxin.

Organic synthesis

Chemical synthesis could involve (a) synthesis of analogs of natural compounds in an effort to improve affinity, specificity, or potency to improve the safety and efficacy profile of the original natural compound; (b) synthesis of a natural molecule from a more abundantly available intermediate to reduce cost and/or improve purity (e.g., taxotere was developed to overcome the supply problems with taxol); or (c) synthesis of a new, unique chemical structure.

Synthesis of analogs of natural compounds is exemplified by the following: carboplatin—an analog of cisplatin with reduced renal toxicity, doxorubicin—an analog of daunomycin with lower cardiotoxicity, and topotecan—an analog of camptothecin with lower toxicity. Synthesis of analogs of known drugs is sometimes aimed at improving the targeting and the pharmacokinetics of a drug. The tauromustine couples a nitrosourea anticancer agent to a brain-targeting peptide.

Synthesis of new molecular entities (NMEs) that are analogs of known compounds or completely novel structures involves computer modeling of drug–receptor interactions, followed by synthesis and evaluation by using tools such as solid-state and combinatorial chemistry. For example, methotrexate and 5-fluorouracil were developed as analogs of natural compounds that demonstrated anticancer activity.

Animal sources

The use of animals in the production of various biologic products, including serum, antibiotics, and vaccines, has life-saving significance. Hormonal substances, such as thyroid extract, insulin, and pituitary hormones obtained from the endocrine glands of cattle, sheep and swine, are lifesaving drugs used daily as replacement therapy.

Genetic engineering

In addition to the use of whole animals, cultures of cells and tissues from animal and human origin are routinely used for the discovery and development of new drugs—both small molecules and biologicals, such as vaccines. Drugs that were traditionally produced in animals are increasingly being synthesized by using cell and tissue cultures. The two basic technologies that drive the genetic field of drug development are recombinant DNA technology and monoclonal antibody production.

Recombinant DNA technology involves the manipulation of cellular DNA to produce desired proteins, which may then be extracted from cell cultures for therapeutic use. Recombinant DNA technology has the potential to produce a wide variety of proteins. For example, human insulin, human growth hormone, hepatitis B vaccine, and interferon are produced by recombinant DNA technology.

A growing class of biologics is monoclonal antibodies against cellular targets aimed for destruction, such as molecular markers on tumors. Monoclonal antibodies target a single epitope, an antigen surface recognized by the antibody, as against natural polyclonal antibodies, which bind to different epitopes on one or more antigen molecules. This confers a high degree of specificity to monoclonal antibodies.

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While recombinant DNA techniques usually involve protein production within cells of lower animals, monoclonal antibodies are produced in cells of higher animals, sometimes in the patient, to ensure the lack of patient immune reaction against these macromolecules on administration.

Monoclonal antibodies are used as anticancer therapeutics, in home pregnancy testing products, and for drug targeting to specific sites within the body. In home pregnancy testing products, the monoclonal antibody used is highly sensitive to binding at one site of the human chorionic gonadotropin (HCG) molecule, a specific marker to pregnancy because HCG is synthesized exclusively by the placenta.

Gene therapy

Gene therapy is the process of correction or replacement of defective genes and has the potential to be used to prevent, treat, cure, diagnose, or mitigate human disease caused by genetic disorders. Oligonucleotides and small interfering RNA (siRNA) are used to inhibit aberrant protein production, whereas gene therapy aims at expressing therapeutic proteins inside the body.

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