A QSAR Study for Analgesic and Anti‐inflammatory Activities of 5‐/6‐Acyl‐3‐alkyl‐2‐Benzoxazolinone Derivatives

Abstract

This paper is dedicated to Prof. Paola Gramatica on the occasion of her retirement.Abstract: In this publication, QSAR models were developed to predict analgesic and anti-inflammatory activities of some 2-benzoxazolinone derivatives using multiple linear regression method. The models were validated internally and externally according to the OECD principles. With the help of these models, pronounced molecular properties of these compounds related to activities were also explored. The developed models demonstrated that hydrophobicity, the number of halogens, and the shape of the molecular structure of these candidate drugs are prominent to represent analgesic and anti-inflammatory activities. Based on the previously tested compounds and the developed models, 77 new compounds were designed as potential analgesic and anti-inflammatory drugs. Majority of the newly designed compounds demonstrated promising analgesic and anti-inflammatory activity.(7 of 9) 1800090 Figure 4. Insubria graph. Predicted vs. leverage values of (a) A activity model and (b) AI activity model.

Quantitative Structure–Activity Relationship (QSAR) Study Predicts Small-Molecule Binding to RNA Structure

“…To fully access the numerous potentially druggable RNA targets, a rational tool for ligand design and a comprehensive understanding of RNA:small-molecule binding details are required. Recently, machine learning-aided mechanistic studies and ligand predictions have shown success in multiple complex tasks, including the design of enantioselective catalysts in organic synthesis and bioactive ligands for kinase inhibition. − Among multiple computational tools, quantitative structure–activity relationship (QSAR) studies can pinpoint guiding principles for a specific target by correlating the experimentally observed binding properties with the molecular descriptors of the ligands. − A robust and predictive QSAR model has been proven to be an efficient tool to predict the activities of small-molecule candidates and to drive hit optimization. Despite its success in protein-based ligand design, however, a few QSAR studies have been conducted for identifying RNA-targeted small molecules. − While significant work has been done to explore key descriptors involved in RNA recognition, − these existing data cannot be used as input for a QSAR approach targeting a specific RNA structure, as these data are derived from disparate methods and RNA targets.…”

Untitled

“…Given that there are several active sites on its basic structure, the 2(3H)-benzoxazolone scaffold plays a significant role in medicinal chemistry. The pharmacological effects of 2(3H)-benzoxazolone derivatives include analgesic [10], anti-inflammatory [10], antiviral [11], antifungal [12], anti-nociceptive [13], anticancer [14], and anticonvulsant [15] effects. Nevertheless, there are very few studies available that examine the cytotoxic and apoptotic effects of compounds based on benzoxazolone.…”

Investigation of some 3-substituted-2(3H)-benzoxazolone derivatives against caspase-3 : A molecular docking study

“…2(3H)-Benzoxazolone derivatives are essential compounds in pharmacological probe development because different chemical alterations can be done at various places in the core structure [5]. The derivatives synthesized over the nitrogen atom in the third position of the benzoxazolone ring have a wide range of biological activity [6]. Compounds with benzoxazolone in their structure have been shown to have analgesic [7], anti-inflammatory [8], antibacterial [9], and cytotoxic [10] properties.…”