Designed 1-Hydroxynaphthalene-2-Carboxanilide Derivatives were evaluated for their Anticancer drug candidate properties by performing a Silico Pharmacokinetic and Silico Toxicological Analysis

Abstract

Cancer continues to be a significant worldwide threat to health and there is a desperate requirement for
more effective and safer anticancer agents. A total of seventy-five 1-hydroxynaphthalene-2-carboxanilide
derivatives were tested systematically evaluated using computer-aided drug design methods in the present
study with reference to Anticancer 1-hydroxynaphthalene-2-carboxanilides with a p53-independent
mechanism of action were designed and synthesized. First, all seventy-five compounds were pre-screened
for physicochemical and pharmacokinetic properties on [SwissADME](https://www.swissadme.ch) and
thirty compounds were chosen for in-depth toxicity and pharmacokinetic analysis on [ADMETlab 3.0]
(https://admetlab3.scbdd.com) with favourable ADME profiles. The study explored various aspects of the
compounds, such as their physiochemical properties, LogP, aqueous solubility, drug kinetic parameters,
drug-likeness, medicinal chemistry accessibility, and toxicity profiles, to thoroughly evaluate their
therapeutic potential. The majority of the compounds showed good oral absorption, moderate water
solubility and good lipophilicity (LogP of < 5.). Drug-likeness evaluation showed that the compounds tested
had minimal rule violations with a consistent bioavailability score of 0.55. The BOILED-Egg model showed
good gastrointestinal absorption and permeability characteristics, and the bioavailability radar showed that
a few derivatives were located in optimal physicochemical area for an oral drug. The toxicity predictions
indicated moderate toxicity profile with some compounds being low in hepatotoxicity and cardiotoxicity
risk. In addition, the compounds selected were expected to not be substrates of P-glycoprotein, resulting
in good membrane transport properties. Based on the integrated ADME and ADMET analysis, the five
compounds (3, 14, 15, 16 and 26) were selected as the most suitable lead candidates for further drug
development and evaluation as anticancer agents with balanced pharmacokinetic and safety profile. The
results of this study indicate that in the future, 2-hydroxynaphthalene-3-carboxanilide derivatives can be
used as scaffolds for designing new cancer drugs. Such derivatives can be capable of possessing better drug
like properties.