ABSTRACT
A quantitative structure-activity relationship (QSAR) model was built from a dataset of 54 peptide-type compounds as SARS-CoV inhibitors. The analysis was executed to identify prominent and hidden structural features that govern anti-SARS-CoV activity. The QSAR model was derived from the genetic algorithm-multi-linear regression (GA-MLR) methodology. This resulted in the generation of a statistically robust and highly predictive model. In addition, it satisfied the OECD principles for QSAR validation. The model was validated thoroughly and fulfilled the threshold values of a battery of statistical parameters (e.g. r 2 = 0.87, Q 2 loo = 0.82). The derived model is successful in identifying many atom-pairs as important structural features that govern the anti-SARS-CoV activity of peptide-type compounds. The newly developed model has a good balance of descriptive and statistical approaches. Consequently, the present work is useful for future modifications of peptide-type compounds for SARS-CoV and SARS-CoV-2 activity.
Subject(s)
Antiviral Agents , Betacoronavirus/drug effects , Peptides , Quantitative Structure-Activity Relationship , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Betacoronavirus/enzymology , Coronavirus 3C Proteases , Cysteine Endopeptidases , Inhibitory Concentration 50 , Linear Models , Molecular Structure , Peptides/chemistry , Peptides/pharmacology , SARS-CoV-2 , Viral Nonstructural Proteins/antagonists & inhibitorsABSTRACT
Human African trypanosomiasis (HAT) is prevalent in African countries, covering 37 countries, mostly sub-Saharan. A limited number of drugs are available to cure this neglected disease. In the present work, quantitative structure-activity (toxicity) relationships (QSA(T)R) analysis has been performed for a dataset of 54 6-arylpyrazine-2-carboxamides as Trypanosoma brucei inhibitors to identify the important structural features required for future optimization of lead candidates. The QSA(T)R models satisfy OECD guidelines and have high statistical robustness. The QSA(T)R models are based on easily interpretable molecular descriptors. The QSA(T)R models indicate that Trypanosoma brucei inhibitory activity of 6-arylpyrazine-2-carboxamides has correlation with the presence of N-sec-butylformamide and substituted benzene. The results could be beneficial for further optimization of 6-arylpyrazine-2-carboxamides as Trypanosoma brucei inhibitors. Some potential candidate molecules have been proposed.
Subject(s)
Antiprotozoal Agents/chemistry , Antiprotozoal Agents/pharmacology , Pyrazines/chemistry , Pyrazines/pharmacology , Quantitative Structure-Activity Relationship , Trypanosoma brucei brucei/drug effects , Models, Molecular , Molecular StructureABSTRACT
Polyphenols are natural compounds that show a wide spectrum of biological actions potentially beneficial for the human health. Wine is an alcoholic beverage that contains a large amount of polyphenols extracted from grapes during the processes of vinification. These molecules are associated with anticancerogenic, antidiabetic, neuroprotective, hormonal, antimicrobial, cardioprotective, and other health effects of wine. The present review provided an overview of well know and recent achievement in analytical methodology for the analysis of polyphenols in wine, and their biological activities.
