Topological Polar Surface Area, Molecular Weight, and Rotatable Bond Count Account for the Variations in the Inhibitory Potency of Antimycotics against Microsporum canis

Antifungal agents are the group of drugs commonly prescribed in the treatment of fungal infections, which are widely spread among the global population. Their properties, such as absorption, distribution, metabolism, route of elimination or plasma protein binding (PPB), considerably influence their therapeutic success, while a number of the molecular physicochemical properties of the drug notably influence all these processes. Lipophilicity (log P), molecular weight (Mw), volume (Vol), polar surface area (PSA) and solubility (log S) play important roles in drug absorption, penetration into tissues, distribution and route of elimination or the degree of plasma protein binding. In this study, the relationships between these five molecular properties of eight antifungal drugs and their plasma protein binding data obtained from relevant literature were investigated. The Selected physicochemical molecular descriptors of the drug were calculated using software packages. The established relationships between PPB and PSA; Mw; Vol and log S were showed relatively poor correlation (r < 0.35). The best correlation was obtained for the relationship between PPB data and the lipophilicity descriptor X log P3 (correlation coefficient r = 0.55). In further investigation, multiple linear regression analysis was applied. The best correlation was obtained with application of lipophilicity with polar surface area (r = 0.918) and volume (r = 0.916) or molecular weight (r = 0.896) as independent variables.

Download Full-text

MOLECULAR DOCKING AND PHARMACOKINETIC PREDICTION OF HERBAL DERIVATIVES AS MALTASE-GLUCOAMYLASE INHIBITOR

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i9.19337 ◽

2017 ◽

Vol 10 (9) ◽

pp. 392 ◽

Cited By ~ 1

Author(s):

Peter Juma Ochieng ◽

Tony Sumaryada ◽

Daniel Okun

Keyword(s):

Molecular Docking ◽

Surface Area ◽

Docking Studies ◽

Polar Surface Area ◽

Autodock Vina ◽

Standard Drug ◽

Lipinski’S Rule ◽

Structure Activity ◽

Topological Polar Surface Area ◽

High Binding Affinity

Objective: To perform molecular docking and pharmacokinetic prediction of momordicoside F2, beta-sitosterol, and cis-N-feruloyltyramine herbal derivatives as maltase-glucoamylase (MGAM) inhibitors for the treatment of diabetes.Methods: The herbal derivatives and standard drug miglitol were docked differently onto MGAM receptor using AutoDock Vina software. In addition, Lipinski’s rule, drug-likeness, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties were analyzed using Molinspiration, ADMET structure–activity relationship, and prediction of activity spectra for substances online tools.Results: Docking studies reveal that momordicoside F2, beta-sitosterol, and cis-N-feruloyltyramine derivatives have high binding affinity to the MGAM receptor (−7.8, −6.8, and −6.5 Kcal/Mol, respectively) as compared to standard drug miglitol (−5.3 Kcal/Mol). In addition, all the herbal derivatives indicate good bioavailability (topological polar surface area <140 Ȧ and Nrot <10) without toxicity or mutagenic effects.Conclusion: The molecular docking and pharmacokinetic information of herbal derivatives obtained in this study can be utilized to develop novel MGAM inhibitors having antidiabetic potential with better pharmacokinetic and pharmacodynamics profile.

Download Full-text

Discovery of a Potent Free Fatty Acid 1 Receptor Agonist with Low Lipophilicity, Low Polar Surface Area, and Robust in Vivo Efficacy

Journal of Medicinal Chemistry ◽

10.1021/acs.jmedchem.5b01962 ◽

2016 ◽

Vol 59 (6) ◽

pp. 2841-2846 ◽

Cited By ~ 17

Author(s):

Steffen V. F. Hansen ◽

Elisabeth Christiansen ◽

Christian Urban ◽

Brian D. Hudson ◽

Claire J. Stocker ◽

...

Keyword(s):

Fatty Acid ◽

Free Fatty Acid ◽

Surface Area ◽

Receptor Agonist ◽

Polar Surface Area ◽

In Vivo Efficacy ◽

Polar Surface

Download Full-text

The effect of the solvent nature on the quinoline derivatives physicochemical characteristics

Butlerov Communications ◽

10.37952/roi-jbc-01/19-60-11-31 ◽

2019 ◽

Vol 60 (11) ◽

pp. 31-39

Author(s):

Vladimir V. Shcherbakov ◽

◽

Svetlana V. Kurbatova ◽

Margarita N. Zemtsova ◽

◽

...

Keyword(s):

Dipole Moment ◽

Surface Area ◽

Chemical Nature ◽

Solvation Energy ◽

Biologically Active ◽

Quinoline Derivatives ◽

Polar Surface Area ◽

Polar Surface ◽

Solvent Nature ◽

Derivatives Of

The influence of the solvent nature on some physicochemical parameters of the quinoline derivatives molecules is investigated. It was noted that a variety of intermolecular interactions arising between the dissolved substance and the solvent and often accompanied by the phenomena of solvation, association, etc. leads to a variety of structural and energy changes in such systems and complicating their description. The most urgent problems of solutions include issues related to the solubility and bioavailability of biologically active compounds and drugs, the study of their ability to dissolve, the permeability of biological barriers, targeted delivery, etc., as well as the problems associated with the study of sorption of organic compounds from aqueous-organic eluents, for example, in liquid chromatography. Derivatives of quinoline (4-carboxy- and 4-aminoquinoline), known as potential drugs with various types of pharmacological action, were used as research objects. Using quantum chemical calculations, the dipole moment of the amino and carboxy derivatives of quinoline was determined, and the data obtained for vacuum and in solvents of various chemical nature were compared. A significant effect of solvent polarity on the dipole moment of quinoline derivatives dissolved in these solvents was found. The values of the solvation energy of quinoline derivatives in solvents of various chemical nature are calculated. It is shown that a change in the solvation energy is determined both by the structure of the molecules of the quinoline derivatives and by the polarity of the solvent. A nonlinear change in the energy of solvation with a change in the polarity of the solvent is established. A comparison is made of the values of the quinoline derivatives molecules polar surface area in solvents of various chemical nature. It was found that the polar surface area of the studied compounds changes slightly with a change in the nature of the solvent.

Download Full-text