![]() ![]() Additionally, about half of all proteins contain a metal 31 which are required to carry out their functions. These metalloenzymes are carbonic anhydrase, Vitamin B12-dependent enzymes, nitrogenase, superoxide dismutase, chlorophyll-containing proteins, hydrogenases, ribozyme and deoxyribozyme, and matrix metalloproteinases. In all metalloenzymes, the metal ion catalyzes reactions that are difficult to achieve in organic chemistry. The shape of the active site in all enzymes is crucial. In all metalloenzymes, the metal ion is bound to the protein with one labile coordination site, and the metal ion is usually located in a pocket whose shape fits the substrate. There are a large number of enzymes that contain metals and such enzymes are known as metalloenzymes. All direct structural analogs of cisplatin produce a very similar array of adducts on target DNA and thus they all induce similar biological consequences and may have a spectrum of clinical activity genuinely complementary to the parent drug even though structurally dissimilar. 14 Satraplatin is a direct analog of cisplatin (1). However, despite the reputed inertness of Pt (IV) compounds, satraplatin undergoes rapid biotransformation in human red blood cells. Satraplatin (5, JM216), another platinum-based antineoplastic agent, is under investigation for the treatment of advanced prostate cancer, but it has not yet received approval from the U.S. ![]() 12, 13 It had been earlier used in Europe for a number of years. Further attempt to reduce the toxicity and drug resistance led to develop a new drug oxaliplatin (4) which was finally granted approval for use in the US in August 2002 for colorectal cancer in combination with 5-fluorouracil (5-FU). In fact, for some tumors cisplatin was still to be therapeutically more effective than carboplatin. Consequently, another compound, carboplatin (3), was developed which had slightly low toxicity but its effectiveness to cancer was not much superior to cisplatin. ![]() 7–9 However, some cancers were found to be resistant to cisplatin, 10‒11 and additionally several side effects were found to be associated with it. Cisplatin is used to treat germ-cell cancers, gestational trophoblastic tumors, epithelial ovarian cancer, and small cell lung cancer as well as for the palliation of bladder, cervical, nasopharyngeal, esophageal, and head and neck cancers. In addition to cisplatin (1), there are several drugs that are complexed with platinum. Now we present here in brief some description of drugs that contain metals and also the enzymes that essentially require metals. Metals can serve to bind and orient substrate with respect to functional groups in the active site. 6 Without appropriate metal ion, a biochemical reaction catalyzed by a particular metalloenzyme may proceed very slow. ![]() Metals ions also play essential roles in a variety of enzymes and control enzyme-catalyzed reactions by modifying electron flow in substrates or enzymes. Two most important drugs, cisplatin (1) and auranofin (2), are widely used for the treatment of genitourinary and head and neck tumors, respectively. The drug industry has not relied only on essential metal ions but also on other metals. The most important aspect of metal ions is their use in drug discovery. 1‒5 Thus, now-a-days, the important aspect of medicinal bioinorganic chemistry is related to study at the molecular level the diseases caused by the deficiency or excess of the various metal ions and to find their remedy. The deficiency of Fe and Co leads to anemia, that of Cu leads to brain and heart diseases and anemia, that of Zn leads to growth retardation and skin changes, that of Ca leads to bone deterioration, and that of Cr reduces the glucose tolerance. Among these metals, the most notable that usually exist in the form of ions, are Fe, Co, Ni, Ca, Cu, Zn, and Cr. Among the metals that are currently known to be essential for normal biological functions in humans are sodium (Na), potassium (K), magnesium (Mg), and calcium (Ca) that belong to main group of elements, and vanadium (V), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), molybdenum (Mo), and cadmium (Cd) that belong to transition metal group of elements in periodic table. Essential metal ions can also be toxic if present in excess, but their presence is crucial for survival. However, a few metal ions, particularly the so called heavy metal ions, such as mercury and lead, can be dangerous due to their toxic effects. Metal ions are required to keep the human body healthy because several critical biological functions in humans depend upon their presence, and their absence or scarcity may lead to diseases. ![]()
0 Comments
Leave a Reply. |