Physicochemical Properties in Relation to Biological Action - Protein binding, Chelation, Bioisosterism, Optical and Geometrical isomerism : Pharmaguideline

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Physicochemical Properties in Relation to Biological Action - Protein binding, Chelation, Bioisosterism, Optical and Geometrical isomerism

The drug can attach to a single or several blood proteins, depending on whether it is a weak or strong acid, basic, or neutral.

 Protein Binding

  • The drug can attach to a single or several blood proteins, depending on whether it is a weak or strong acid, basic, or neutral.
  • Albumin, which accounts for half of all blood proteins, is the most important protein involved in drug binding.
  • Protein binding measurements are often expressed as a percentage of total plasma drug concentration that is bound to all plasma proteins. The amount to which a medication is linked to plasma proteins can influence drug distribution in a variety of ways.
  • The drug-protein combination does not pass across phospholipid bilayers such as capillary membranes, glomerular membranes in the kidney, and the blood-brain barrier.
  • The enzymes involved in first pass metabolism are also less accessible to bound drugs. Reversible drug protein complexes serve as a store that replenishes the concentration of the drug when metabolism and excretion have removed most of the free drug.
  • As a result, medicines with high protein binding activity levels have a longer half-life than those with low values. These elements may cause extended activity, which may be beneficial or may encourage the onset of negative side effects.

Chelation

  • Chelates are chemicals that are formed by donating electrons to metal ions and forming a ring structure.
  • Ligands are compounds that may form a ring structure with metal ions.
  • Most metals may form chelates or complexes, but the chelating ability is limited to electron-donating atoms such as N, S, and O.
  • Chelation is a process that plays an important role in biological systems and, to some extent, in understanding pharmacological action.
  • Penicillamine is effective against copper poisoning because it forms chelates with copper and other metal ions.

Biosiosterism

The application of isosterism to the modification of biological activity has given rise to the term bioisosterism. Bioisosteres are chemical substituents or groups with comparable physical or chemical characteristics that cause biological qualities that are generally similar to another chemical substance. Bioisosterism is used to lower toxicity, adjust bioavailability, or vary the activity of a lead molecule, and it may also affect the lead's metabolism.

Classical bioisosteres - As a result of atoms with the same electron configuration sharing the same biological capabilities, James Moir developed the classical concept of bioisostery, which was later improved by Irving Langmuir. The substitution of a fluorine atom for a hydrogen atom at a metabolic oxidation site may prevent such metabolism in a therapeutic candidate. Since fluorine and hydrogen are both identical in size, the molecule's overall structure remains unaltered, allowing the necessary biological function to take place. However, if the metabolic route is inhibited, the medication candidate may have a prolonged half-life.

Non-classical bioisosteres - non-classical bioisosteres may differ from classical bioisosteres in a variety of ways, but they all have the goal of delivering a comparable steric and electronic profile to the original functional group. In nonclassical bioisosteres, the binding requirements of the ligand determine the kind of functional group that is used. For example, an alkyl group may replace a cyclic moiety, an alkyl group may replace a complex heteroatom moiety, or other changes go beyond simple atom-for-atom substitutions.

Optical and Geometrical Isomerism

A molecule's physicochemical properties are dictated not only by the existence of functional groups in the molecule, but also by the specific arrangement of these groups. The human body, for example, exposes molecules to an asymmetric environment.

A compound's ability to spin planar polarized light is what distinguishes it from an optical isomer. It is determined that optical isomers have differing biological activities according to their ability to respond preferentially at an asymmetrical center within a biological system.

Geometric isomerism - This is a sort of diastereoisomer that occurs as a result of constrained rotation around a bond, such as in olefinic compounds. Geometric isomerism does not always result in optical isomerism in a compound. If the structure is asymmetric (or dissymmetric), geometric isomers can display optical activity.

It may be difficult to explain variations in biologic activity only to differences in isomer specific organization, as opposed to enantiomers. The observed differences in biological activity of geometric isomers could be explained by variations in the interatomic distance between groups. Diethylstilboestrol is a popular example, a drug synthesized to mimic the natural estrogen Estradiol. There is a 14-fold estrogenic increase in diethylstilboestrol trans as compared to its cis isomer.
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Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of pharmaguideline.com, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
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