What is the pharmacophore of a drug?

“A pharmacophore is the ensemble of steric and electronic features that is necessary to ensure the optimal supramolecular interactions with a specific biological target structure and to trigger (or to block) its biological response.”

What is an example of a pharmacophore?

An example of a pharmacophore model of the benzodiazepine binding site on the GABAA receptor. White sticks represent the carbon atoms of the benzodiazepine diazepam, while green represents carbon atoms of the nonbenzodiazepine CGS-9896.

How do you identify a pharmacophore in a molecule?

The pharmacophore can be relatively easily identified if the 3D structure structure is available for several ligands bound to the same binding site of the same protein by aligning the features of all the ligands and finding their largest common arrangement, referred to as the common pharmacophore (CP).

What is the pharmacophore of penicillin?

The pharmacophore (part of a molecule that confers pharmacological activity) of penicillins is called the penicillin nucleus. It contains a β-lactam ring.

What is Auxochrome in chemistry?

An auxochrome is a functional group of atoms with one or more lone pairs of electrons when attached to a chromophore, alters both the wavelength and intensity of absorption.

Is the beta-lactam ring a pharmacophore?

Accordingly, the pharmacophore of β-lactam antibiotics is considered to comprise both the β-lactam ring (which is strained and therefore contains an electrophilic carbonyl for attack by the PBP) and the C-2 carboxylic acid, which mimics the C-terminal acid of the native peptide chain.

What is the target for clavulanic acid?

Clavulanic acid from a clinical point of view can target two enzymes (L, D-TP and β-lactamase) simultaneously, which could be a potential candidate to treat drug, multi-drug resistant bacteria and other bacterial infections as combination therapy.

What are Auxochromes and chromophores?

Auxochromes are a bunch of atoms that when combined with an appropriate chromophore heighten or enhance the color. Chromophores are constituents of molecules that absorb or reflect certain colors when light fall on them. They are used together to make dyes.

What are Auxochromes give examples?

Examples include the hydroxyl group (−OH), the amino group (−NH2), the aldehyde group (−CHO), and the methyl mercaptan group (−SCH3). An auxochrome is a functional group of atoms with one or more lone pairs of electrons when attached to a chromophore, alters both the wavelength and intensity of absorption.

What is β-lactam ring?

A beta-lactam (β-lactam) ring is a four-membered lactam. A lactam is a cyclic amide, and beta-lactams are named so because the nitrogen atom is attached to the β-carbon atom relative to the carbonyl. The simplest β-lactam possible is 2-azetidinone.

How does beta-lactamase inactivate ampicillin?

The beta-lactamase enzymes inactivate beta-lactam antibiotics by hydrolyzing the peptide bond of the characteristic four-membered beta-lactam ring rendering the antibiotic ineffective. The inactivation of the antibiotic provides resistance to the bacterium.

How does clavulanic acid deactivate lactamase?

Clavulanic acid is a suicide inhibitor, covalently bonding to a serine residue in the active site of the β-lactamase. This restructures the clavulanic acid molecule, creating a much more reactive species that attacks another amino acid in the active site, permanently inactivating it, and thus inactivating the enzyme.

How does clavulanate work?

It works by stopping the growth of bacteria. Clavulanic acid is in a class of medications called beta-lactamase inhibitors. It works by preventing bacteria from destroying amoxicillin.

What is the role of auxochrome?

An auxochrome is a functional group of atoms attached to the chromophore which modifies the ability of the chromophore to absorb light, altering the wavelength or intensity of the absorption.

What do u mean by auxochrome?

An auxochrome is a group of atoms attached to a chromophore which modifies the ability of that chromophore to absorb light. They themselves fail to produce the colour; but when present along with the chromophores in an organic compound intensifies the colour of the chromogen.

How do beta-lactams inhibit Transpeptidase?

Inhibition of transpeptidase activity by β-lactam antibacterials prevents the bacterium from synthesising an intact cell wall when it divides. The transmembrane osmotic gradient then leads to swelling, rupture and death of the bacterium. Some bacterial cells also contain enzymes that cause cell lysis when activated.

What is a pharmacophore?

IUPAC defines a pharmacophore to be “an ensemble of steric and electronic features that is necessary to ensure the optimal supramolecular interactions with a specific biological target and to trigger (or block) its biological response”. A pharmacophore model explains how structurally diverse ligands can bind to a common receptor site.

How are pharmacophore models used in drug discovery?

Furthermore, pharmacophore models can be used to identify through de novo design or virtual screening novel ligands that will bind to the same receptor. An example of a pharmacophore model of the benzodiazepine binding site on the GABA A receptor.

Which pharmacophore features are highlighted in the yellow circles?

Note the aligned pharmacophore features are highlighted in small yellow circles (Fig d). Fig a was obtained from pharmmapper, while Fig b, c and d were obtained using LigandScout 2.0. Structural Analysis of Docked complexes

What is the pharmacophore model in VSA?

A validated pharmacophore model serves as a template to search a large database of ligands to derive novel scaffolds bearing chemical features similar to the query pharmacophore. Handling of the conformational flexibility of database ligands and pharmacophore mapping are the two major steps in VS.