What is HBA and HBD?

What is HBA and HBD?

Alcohol and phenol hydroxyls are common in drugs and are often involved in hydrogen bonding, the oxygen as a H-bond acceptor (HBA) and the hydrogen as hydrogen-bond donor (HBD). Bond directions must be considered; slight deviations are possible. Such bonds are generally important in drug-target binding.

What does log p tell you about a drug?

The Log P value of the compound indicates the permeability of the drugs to reach the target tissue in the body. All the investigated compounds are lipophilic because the Log P > 0 (or P > 1) (Table 3).

What is the rule of 5 in drug discovery?

In the drug discovery setting, the Rule of 5 predicts that poor absorption or permeation is more likely when there are more than 5 H-bond donors, 10 H-bond acceptors, the molecular weight is greater than 500, and the calculated Log P (CLog P) is greater than 5.

What is drug-likeness screening?

As defined earlier, “drug-likeness” assesses qualitatively the chance for a molecule to become an oral drug with respect to bioavailability. Drug-likeness was established from structural or physicochemical inspections of development compounds advanced enough to be considered oral drug-candidates.

What are hydrogen bond donors?

Hydrogen bond donor: A bond or molecule that supplies the hydrogen atom of a hydrogen bond. A generic hydrogen bond. X-H is the hydrogen bond donor (shown in red) and A is the hydrogen bond acceptor.

Is menthol a hydrogen bond donor?

All-atom molecular dynamics simulations have been employed to study deep eutectic solvents (DESs) consisting of thymol or naphthol as hydrogen bond donor (HBD) and menthol as hydrogen bond acceptor (HBA).

What does negative logD mean?

What does a negative log D mean? Negative values of logD (-1.44 to 0) in the physiologically relevant pH range (pH 1–8) lead us to conclude that this compound would be more susceptible to higher aqueous solubility and of lower lipophilicity in the body. As a result we would expect membrane permeability to be poor.

How does logP affect drug absorption?

High lipophilicity (logP>5) often contributes to high metabolic turnover, low solubility, and poor oral absorption. In addition, highly lipophilic compounds tend to bind to hydrophobic targets other than the desired target, and, therefore, there is an increased risk of promiscuity and toxicity.

What is clog P?

The logP value of a compound, which is the logarithm of its partition coefficient between n-octanol and water log(coctanol/cwater), is a well established measure of the compound’s hydrophilicity. Low hydrophilicities and therefore high logP values cause poor absorption or permeation.

Why is Lipinski’s Rule important?

The rule is important to keep in mind during drug discovery when a pharmacologically active lead structure is optimized step-wise to increase the activity and selectivity of the compound as well as to ensure drug-like physicochemical properties are maintained as described by Lipinski’s rule.

What is bioavailability score?

The bioavailability score (BA score) is a determinant of oral absorption of drug substances. Any drug molecules satisfying the ‘rule of five’ with a BA score of 0.55 are considered as sufficiently absorbable via oral route [49] . All of the prodrugs scored 0.55, thus demonstrating good oral bioavailability. …