Related Experiment Video
Updated: Feb 11, 2026
In Silico Modeling Method for Computational Aquatic Toxicology of Endocrine Disruptors: A Software-Based Approach Using QSAR Toolbox
Published on: August 28, 2019
The anesthetic action of some polyhalogenated ethers-Monte Carlo method based QSAR study
Mlađan Golubović1, Milan Lazarević2, Dragan Zlatanović3
1Center for Anesthesiology and Reanimatology, Clinical Center Niš, Niš, Serbia.
Abstract:
Up to this date, there has been an ongoing debate about the mode of action of general anesthetics, which have postulated many biological sites as targets for their action. However, postoperative nausea and vomiting are common problems in which inhalational agents may have a role in their development. When a mode of action is unknown, QSAR modelling is essential in drug development. To investigate the aspects of their anesthetic, QSAR models based on the Monte Carlo method were developed for a set of polyhalogenated ethers. Until now, their anesthetic action has not been completely defined, although some hypotheses have been suggested. Therefore, a QSAR model should be developed on molecular fragments that contribute to anesthetic action. QSAR models were built on the basis of optimal molecular descriptors based on the SMILES notation and local graph invariants, whereas the Monte Carlo optimization method with three random splits into the training and test set was applied for model development. Different methods, including novel Index of ideality correlation, were applied for the determination of the robustness of the model and its predictive potential. The Monte Carlo optimization process was capable of being an efficient in silico tool for building up a robust model of good statistical quality. Molecular fragments which have both positive and negative influence on anesthetic action were determined. The presented study can be useful in the search for novel anesthetics.
Insights
Quantitative Structure-Activity Relationship (QSAR) models were developed to understand general anesthetic action. This research identified key molecular fragments influencing anesthetic effects, aiding the search for new anesthetic drugs.
Area of Science:
- Pharmacology
- Medicinal Chemistry
- Computational Chemistry
Background:
- The precise mechanism of action for general anesthetics remains debated, with multiple biological targets proposed.
- Postoperative nausea and vomiting are frequent complications potentially linked to inhalational anesthetic agents.
Purpose of the Study:
- To develop Quantitative Structure-Activity Relationship (QSAR) models for polyhalogenated ethers to elucidate their anesthetic properties.
- To identify specific molecular fragments contributing to anesthetic action, given the incomplete understanding of their mechanism.
Main Methods:
- QSAR models were constructed using optimal molecular descriptors derived from SMILES notation and local graph invariants.
- The Monte Carlo optimization method with random training/test set splits was employed for model development.
- Model robustness and predictive potential were assessed using various statistical methods, including the Index of ideality correlation.
Main Results:
- A robust QSAR model with good statistical quality was successfully developed using in silico methods.
- Specific molecular fragments were identified as having both positive and negative influences on anesthetic activity.
- The Monte Carlo optimization proved effective for building reliable predictive models.
Conclusions:
- The study provides valuable insights into the structure-activity relationships of general anesthetics.
- The identified molecular fragments can guide the design and discovery of novel anesthetic agents.
- QSAR modeling serves as an essential tool in drug development when mechanisms of action are not fully understood.
Related Concept Videos
01:23Local Anesthetics: Mechanism of Action
Local anesthetics are amphiphilic molecules consisting of a hydrophobic aromatic part linked to a hydrophilic group by an ester or amide linkage. They are weak bases and are usually available as salts, which increases their solubility and stability. Once administered, LAs exist in the body either...
02:29Ethers from Alcohols: Alcohol Dehydration and Williamson Ether Synthesis
Ethers can be prepared from organic compounds by various methods. Some of them are discussed below,
Preparation of Ethers by Alcohol Dehydration
In this method, in the presence of protic acids, alcohol dehydrates to produce alkenes and ethers under different conditions. For example, in the presence of sulphuric acid, dehydration of ethanol at 413 K yields ethoxyethane, whereas it yields ethene at 443 K.
02:36Crown Ethers
02:28Structure and Nomenclature of Ethers
Ethers are organic compounds with an ether functional group which is characterized by an oxygen atom connected to two — identical or different — alkyl, aryl, or vinyl groups. The C–O–C linkage in dimethyl ether — the simplest ether — has an approximately tetrahedral bond angle of 110.3 degrees. The oxygen atom is sp3- hybridized, with the C–O distance being about 140 pm.
Classification of Ethers
Based on their attached substituent...
02:17Physical Properties of Ethers
An ether molecule has a net dipole moment due to the polarity of C–O bonds. Subsequently, boiling points of ethers are lower than those of alcohols of comparable molecular weight and slightly higher than those of hydrocarbons of comparable molecular weight (Table 1).
Ethers can act as hydrogen bond acceptors, making them more water-soluble than hydrocarbons, but since ethers cannot act as hydrogen bond donors, they are much less soluble in water than alcohols. Ethers are considered...
01:06Fixed Action Patterns