Importance of Stereochemistry manik
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1. The document discusses the importance of stereochemistry in pharmacy. Biological systems often have a preference for specific stereoisomers of drugs. For example, only the L-forms of amino acids are used in protein synthesis. 2. Drug efficacy, side effects, and toxicity can be stereospecific. Only one enantiomer of drugs like statins are used clinically as the "eutomer", while the other "distomers" may not have the desired effects or could even be harmful. 3. Biological receptors like enzymes are also chiral and will only interact with one stereoisomer of a drug. This is why drugs are often administered as single enantiomers rather than racemic mixtures.
Importance of Stereochemistry manik
- 1. Medicinal Chemistry: Stereochemistry Prepared By: Md. Imran Nur Manik; B.Pharm; M.Pharm Page 1 [email protected];Lecturer; Department of Pharmacy; Northern University Bangladesh. Importance of studying stereochemistry in pharmacy 1. In biological system there is a preference of a specific stereoisomer. For example – a. There are 20 (or 23) proteogenic (protein synthesizing) amino acids. Among them, only glycine doesn’t have stereoisomers. The remaining amino acids have L- and D- forms but only the L- form is proteogenic. b. Most sugars (e.g. glucose, fructose) occur naturally as the D-form. 2. There are numerous evidences that efficacy, adverse effects and toxicity of drugs may be enantiospecific. For example: Atorvastatin, fluvastatin and rosuvastatin are drugs used for treatment of hypercholesterolemia. These three statins exist in four optical forms, but they are currently used as enantiopure drugs, i.e., only one single enantiomer. 3. The biological receptors (including enzymes) for drugs are chiral. Therefore they respond to only one isomer of a ligand/drug. The isomer with desired biological activity is called eutomer and the other isomers are called distomer. 4. Calcium channel blockers prevent calcium from entering cells of the heart and blood vessel walls, resulting in lower blood pressure. Calcium channel blocker such as Diltiazem and verapamil are both chiral, possessing asymmetric centers. In each case, the dextro-rotatory (i.e. the (+)-enantiomer) is approximately 10 times more potent as a calcium channel blocker than the levo-rotatory (i.e. (–)-enantiomer ).Amlodipine is used therapeutically as a racemic mixture, composed of S- and R-enantiomers, but its calcium channel-blocking effect is confined to S-amlodipine; R-amlodipine has 1000-fold less activity than its S-enantiomer. The affinity of its levorotary (-)-enantiomer to the calcium channels is 1,000 times superior to that of its dextrorotary (+)-enantiomer. Md. Imran Nur Manik
- 2. Medicinal Chemistry: Stereochemistry Prepared By: Md. Imran Nur Manik; B.Pharm; M.Pharm Page 2 [email protected];Lecturer; Department of Pharmacy; Northern University Bangladesh. 5. The enzymes which catalyze most reactions in the body are stereoisomer specific. This is because these enzymes themselves being biomolecules are chiral. This can be explained further. We can see that there is an enzyme with three binding site for an amino acid. If the amino acid was in a non-enzymatic reaction, the stereochemistry is selected by bulky groups’ positions and we will get all the stereoisomers even though one isomer will be preferred. But in an enzymatic reaction, the amino acid has to bind with the specific binding site before catalysis. Thus enzymatic reaction is always stereoisomer specific (other isomers of the molecule may be catalysed by the enzyme if the enzyme has additional binding site, but even then the catalysis is usually weak). Fig. The binding specificity of a chiral receptor site for a chiral molecule is usually only favorable in one way The biological receptors (including enzymes) for drugs are chiral. Therefore they respond to only one isomer of a ligand/drug. The isomer with desired biological activity is called eutomer and the other isomers are called distomer. 6. Chirality is relevant to anaesthesia, simply because more than half of the synthetic agents used in anaesthesia practice are chiral drugs. Almost all these synthetic chiral drugs are administered as racemic mixture, rather than as single pure enantiomers. Examples include inhalational general anaesthetics (e.g. isoflurane), intravenous anaesthetics (e.g. etomidate, thiopentone), neuromuscular blocking agents (e.g. cisatracurium), local anaesthetics (e.g. ropivacaine and levobupivacaine) and other agents (e.g. levosimendan, dexmedetomidine, L-cysteine). Levosimendan Dexmedetomidine Md. Imran Nur Manik