{"id":925,"date":"2020-02-18T10:41:02","date_gmt":"2020-02-18T05:11:02","guid":{"rendered":"https:\/\/medicineplexus.com\/?p=925"},"modified":"2020-02-18T10:41:02","modified_gmt":"2020-02-18T05:11:02","slug":"chirality-of-drugs","status":"publish","type":"post","link":"https:\/\/medicineplexus.com\/chirality-of-drugs\/","title":{"rendered":"Chirality of Drugs"},"content":{"rendered":"\n<p><strong>Chirality of Drugs<\/strong><\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"157\" height=\"118\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-389.png?w=157\" alt=\"\" class=\"wp-image-926\" \/><\/figure>\n\n\n\n<ul><li>Property of a compound whose molecules are not super imposable on their mirror images.<\/li><li>\u00a0Chirality\u00a0 = Handedness.<\/li><li>two isomers are identical in physiochemical properties but different in their ability to rotate plane polarized light.<\/li><li>\u00a0Necessary condition for existence of enantiomers.<\/li><\/ul>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"480\" height=\"180\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-390.png?w=480\" alt=\"\" class=\"wp-image-927\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-390.png 480w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-390-300x113.png 300w\" sizes=\"(max-width: 480px) 100vw, 480px\" \/><\/figure>\n\n\n\n<p><strong>Significance of Chirality<\/strong><\/p>\n\n\n\n<ul><li><strong>Biological activity<\/strong> may reside in <strong>only one of the stereoisomer<\/strong>.<\/li><li>Stereoisomer&#8217;s may show essentially <strong>similar qualitative&nbsp; and&nbsp; quantitative activity.<\/strong><\/li><li>Isomer may exhibit <strong>similar qualitatively but different quantitatively<\/strong>&nbsp; activities.<\/li><li>Isomer may show <strong>distinct pharmacological activity.<\/strong><\/li><\/ul>\n\n\n\n<p><strong>Types of stereoisomers<\/strong><\/p>\n\n\n\n<ul><li>Geometric isomers<\/li><li>Optical isomers<\/li><\/ul>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"490\" height=\"302\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-391.png?w=490\" alt=\"\" class=\"wp-image-928\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-391.png 490w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-391-300x185.png 300w\" sizes=\"(max-width: 490px) 100vw, 490px\" \/><\/figure>\n\n\n\n<ul><li>Because geometric isomers have different chemical and physical properties, they act differently as drugs in our bodies as well.<\/li><\/ul>\n\n\n\n<p>Example :<\/p>\n\n\n\n<ul><li><strong>cis-platin<\/strong>&nbsp; used for chemotherapy&nbsp; &#8211; it can enter cancer cells and interact with DNA<\/li><li><strong>Trans- platin<\/strong>&nbsp; &#8211; not active<\/li><\/ul>\n\n\n\n<p><strong>Optical Isomers<\/strong><\/p>\n\n\n\n<ul><li>have a chiral center (the central carbon in an optical isomer with four bonds each attached to a different group.)<\/li><li>Molecule and mirror image cannot be superimposed into each other even after twisting and turning them.<\/li><li>&nbsp;&nbsp;Identical physical and chemical properties<\/li><li><strong>Enantiomer<\/strong>: another name for a molecule that is found in optical isomers. For example, ibuprofen has a two enantiomers, a <strong>left rotating<\/strong> enantiomer and a <strong>right rotating<\/strong> enantiomer.<\/li><li>&nbsp;&nbsp;&nbsp;<strong>Dextrorotatory<\/strong> (&#8220;+&#8221; \/ \u201cd\u201d form) &#8211; clockwise direction.<\/li><li>&nbsp;&nbsp;&nbsp;<strong>Levorotatory<\/strong> (&#8220;-\u201c \/ \u201cl\u201d form) &#8211; anti-clockwise direction.<\/li><li>Clockwise \u2013&nbsp; <strong>R<\/strong> (rectus).<\/li><li>&nbsp;Anticlockwise \u2013&nbsp; <strong>S <\/strong>(sinister).<\/li><li><strong>Racemic mixture<\/strong>: A mixture of 50% left rotating and 50% right rotating optical isomers<\/li><\/ul>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"480\" height=\"102\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-392.png?w=480\" alt=\"\" class=\"wp-image-929\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-392.png 480w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-392-300x64.png 300w\" sizes=\"(max-width: 480px) 100vw, 480px\" \/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"480\" height=\"82\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-393.png?w=480\" alt=\"\" class=\"wp-image-930\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-393.png 480w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-393-300x51.png 300w\" sizes=\"(max-width: 480px) 100vw, 480px\" \/><\/figure>\n\n\n\n<p><strong>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; STEREOPHARMACOLOGY<\/strong><\/p>\n\n\n\n<ul><li>Affinity of a drug for a specific receptor and its intrinsic activity are related to its chemical structure.<\/li><li>Drug \u2013 receptor interactions are stereo selective.<\/li><li>Minor changes in drug molecule structure.&nbsp;<\/li><li>&nbsp;Major changes in pharmacological properties.<\/li><\/ul>\n\n\n\n<p><strong>Implication:<\/strong><\/p>\n\n\n\n<ul><li>Biomolecules (sugars, amino acids, DNA, proteins, steroids) are chiral<\/li><li>Proteins are built from L-amino acids, which implies that enzymes \u2013 the catalysts of nature &#8211; are chiral<\/li><li>Also, receptors (drug, taste, biopharmaceuticals, agrochemicals) are chiral and the natural ligand to a receptor is often only one specific enantiomer<\/li><li>This is why mirror image molecules can have radically different activities (effectivity, toxicity, taste) in the body.<\/li><li>E.g. olfactory sensors are chiral &#8211; Different smell<\/li><\/ul>\n\n\n\n<ul><li><strong>In 2006 &#8211;<\/strong><\/li><li>80%&nbsp; drugs approved by the FDA were chiral.<\/li><li><strong>75%<\/strong> single enantiomers.<\/li><li><strong>FDA now requires information about the structure and activity of each isomer present<\/strong> in a racemic mixture of a new medication.<\/li><\/ul>\n\n\n\n<p><strong>CHIRAL INVERSION<\/strong><\/p>\n\n\n\n<ul><li>Unique metabolic pathway.<\/li><li>&nbsp;Enzymatic or non-enzymatic.<\/li><li>&nbsp;Involves unidirectional conversion of one enantiomeric form to another.<strong>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;<\/strong><\/li><\/ul>\n\n\n\n<p><strong>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; <em><u>R&nbsp; \u2192&nbsp; S<\/u><\/em><\/strong><\/p>\n\n\n\n<p><strong>CHIRAL SWITCH<\/strong><\/p>\n\n\n\n<ul><li>Development of a single enantiomer from a previously marketed racemate.<\/li><li>&nbsp;Resulted in a number of agents being re-marketed as &nbsp;chiral drugs.<\/li><li>&nbsp;Same or similar therapeutic indications.<\/li><li>Novel indications for old compounds.<\/li><\/ul>\n\n\n\n<p><strong>THALIDOMIDE<\/strong><\/p>\n\n\n\n<ul><li>&nbsp;&nbsp;One asymmetric carbon atom, exists as 2 enantiomers<\/li><li>S-Enantiomer \u2192 sedative<\/li><li><strong>R-Enantiomer <\/strong><strong>\u00ae Teratogen <\/strong><strong>\u00e0 Phocomelia<\/strong><\/li><\/ul>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"480\" height=\"360\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-394.png?w=480\" alt=\"\" class=\"wp-image-931\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-394.png 480w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-394-300x225.png 300w\" sizes=\"(max-width: 480px) 100vw, 480px\" \/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"480\" height=\"360\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-395.png?w=480\" alt=\"\" class=\"wp-image-932\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-395.png 480w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-395-300x225.png 300w\" sizes=\"(max-width: 480px) 100vw, 480px\" \/><\/figure>\n\n\n\n<p><img loading=\"lazy\" decoding=\"async\" width=\"480\" height=\"360\" src=\"\">&nbsp;S-Amlodipine is effective at half the dose of racemate&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;<\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"480\" height=\"360\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-396.png?w=480\" alt=\"\" class=\"wp-image-933\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-396.png 480w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-396-300x225.png 300w\" sizes=\"(max-width: 480px) 100vw, 480px\" \/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"480\" height=\"360\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-397.png?w=480\" alt=\"\" class=\"wp-image-934\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-397.png 480w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-397-300x225.png 300w\" sizes=\"(max-width: 480px) 100vw, 480px\" \/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"480\" height=\"360\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-398.png?w=480\" alt=\"\" class=\"wp-image-935\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-398.png 480w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-398-300x225.png 300w\" sizes=\"(max-width: 480px) 100vw, 480px\" \/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"480\" height=\"360\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-399.png?w=480\" alt=\"\" class=\"wp-image-936\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-399.png 480w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-399-300x225.png 300w\" sizes=\"(max-width: 480px) 100vw, 480px\" \/><\/figure>\n\n\n\n<p>\u00a0\u00a0 <\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"480\" height=\"360\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-400.png?w=480\" alt=\"\" class=\"wp-image-937\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-400.png 480w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-400-300x225.png 300w\" sizes=\"(max-width: 480px) 100vw, 480px\" \/><\/figure>\n\n\n\n<p><\/p>\n\n\n\n<p><strong>ADVANTAGES OF CHIRAL DRUGS<\/strong><\/p>\n\n\n\n<ul><li>Chiral drug is a single agent instead of a mixture of two distinct drugs.<\/li><li>&nbsp;Simplifies the interpretation of the Basic Pharmacology.<\/li><li>&nbsp;Greater selectivity for their biological&nbsp; targets improved therapeutic indices and reduced adverse effects.<\/li><li>&nbsp;Longer or shorter duration of action &#8211;&nbsp; more appropriate dosing frequency.<\/li><li>&nbsp;Decreased inter individual variability.<\/li><\/ul>\n\n\n\n<ul><li><strong>SOME DRUGS ARE BETTER AS RACEMATES &#8211; b&nbsp; BLOCKERS<\/strong><\/li><\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Chirality of Drugs Property of a compound whose molecules are not super imposable on their mirror images. \u00a0Chirality\u00a0 = Handedness. two isomers are identical in physiochemical properties but different in their ability to rotate plane polarized light. \u00a0Necessary condition for existence of enantiomers. Significance of Chirality Biological activity may reside in only one of the[&#8230;]\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_seopress_robots_primary_cat":"","_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","footnotes":""},"categories":[3],"tags":[],"_links":{"self":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/925"}],"collection":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/comments?post=925"}],"version-history":[{"count":0,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/925\/revisions"}],"wp:attachment":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media?parent=925"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/categories?post=925"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/tags?post=925"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}