Page 156 - EJMO-9-1

Eurasian Journal of Medicine and
Oncology
Potential of flavonoids against glioblastoma

Multiple models, including iLOGP, XLOGP3, WLOGP, Cheminformatics tool “Calculation of molecular properties
MLOGP, and SILICOS-IT, assessed lipophilicity. The and bioactivity score” (molinspiration.com), which is
consensus log P was determined to predict membrane renowned for its ability to calculate molecular properties
o/w
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permeability and interaction potential. Water solubility was and bioactivity scores. This comprehensive analysis
calculated using ESOL, Ali, and SILICOS-IT models, with focused on various key biological targets, including G
log S values guiding the prediction of oral bioavailability. protein-coupled receptors (GPCRs), ligand modulators for
Medicinal chemistry filters, such as PAINS and Brenk, ion channels, nuclear receptor ligands, kinase inhibitors,
were applied to identify structural alerts, while synthetic protease inhibitors, and enzyme inhibitors.
accessibility scores predicted the ease of compound To perform this assessment, the phytochemicals, saved
synthesis. Drug likeness was further evaluated using LRF, in MOL format, were submitted as input files into the
Ghose, Veber, and Egan criteria, alongside bioavailability Molinspiration platform. This facilitated the computation
scores. Skin permeability coefficients (log k ) were also of bioactivity scores, allowing us to gain insights into the
p
calculated to assess absorption potential. potential efficacy and interaction of these compounds with
This approach not only enhanced our understanding the targeted biological pathways. The results from this
of the drug-like behavior of the phytochemicals but also evaluation are critical for understanding the therapeutic
identified any possible limitations that could hinder their potential of the phytochemicals and guiding further
research into their pharmacological applications.
development as therapeutic agents. By ensuring that the
compounds met these stringent criteria, we paved the way 2.4.10. DFT calculations
for their potential progression to the next phases of drug
development, reducing the likelihood of costly failures at To explore the molecular characteristics of the isolated
later stages. phytochemicals, we employed DFT using the B3LYP
method in conjunction with a 3-21G basis set. This
2.4.8. Toxicity assessment computational approach allowed us to determine the
optimized molecular conformations of both compounds in
Toxicity assessment is an essential stage in effective drug
development, as it evaluates the potential harmful effects of their energy-minimized ground states. The visualizations
of these optimized structures were carried out using
compounds on living organisms. In our current research, GaussView 5.0.8 software and the Gaussian 09W program. 30
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we undertook a comprehensive toxicity evaluation using
two advanced tools: the Pharmacokinetics and Toxicity In addition to structural optimization, we investigated
Prediction (PkCSM; uq.edu.au) online server and StopTox the frontier molecular orbitals (FMO), molecular
(unc.edu). electrostatic potential (MEP), and various chemical
reactivity descriptors, as established by Koopman’s
The PkCSM online server provides a robust platform 31
for assessing toxicity through various parameters presented theorem. The FMO cubes were further visualized using
VESTA (version 3), enhancing the computational clarity
in both binary yes/no formats and specified units. of our findings. This multifaceted approach provides
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This dual approach enables a nuanced understanding valuable insights into the electronic properties of the
of the toxicological profile of the compounds, allowing phytochemicals, contributing to a deeper understanding
researchers to identify any concerning attributes early in of their potential biological activities and interactions.
the development process.

In addition, we employed StopTox, which incorporates 3. Results
a comprehensive “6-pack” assessment. This tool evaluates 3.1. In vitro results
several critical toxicity endpoints, including acute oral
toxicity, acute dermal toxicity, acute inhalation toxicity, The anticancer activity of compounds isolated from
irritation (skin and eye), skin corrosion, and skin P. chinensis was systematically evaluated using the
sensitization. By utilizing these sophisticated tools, we glioblastoma (U87) cell line, focusing on varying
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aimed to ensure that any potential drug candidates exhibit concentrations (25, 50, and 75 µg/mL) and time points
acceptable safety profiles, thereby mitigating risks associated (24 and 48 h). The results, summarized in Table 1, reveal
with their development and potential clinical application. a compelling dose- and time-dependent inhibition of cell
viability by both compounds.
2.4.9. Bioactivity evaluation At a concentration of 25 µg/mL, Compound 1 exhibited

The bioactivity of the isolated phytochemicals was a modest reduction in cell viability after 24 h of treatment,
thoroughly evaluated using the Molinspiration with an inhibition rate of 10.11%. Notably, this inhibitory

Volume 9 Issue 1 (2025) 148 doi: 10.36922/ejmo.5768