In silico design of novel indolinone-based anticancer agents and proposal of synthetic routes.
6 affiliations
- 1LIMAS Laboratory, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, Morocco.
- 2Engineering Laboratory of Organometallic, Molecular Materials, and Environment (LIMOME). Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, Morocco.
- 3Physical-Chemical Laboratory of Materials, Natural Substances and the Environment (LAMSE), Department of Chemistry, Faculty of Sciences, Techniques of Tangier-University Abdelmalek Essaadi, Tangier, Morocco.
- 4Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India.
- 5Laboratory of Analytical and Molecular Chemistry, Faculty of Sciences Ben M'Sik, Hassan II University of Casablanca, Casablanca, Morocco.
- 6Department of Chemistry, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates.
Abstract
The RAF-MEK-ERK signaling pathway plays a central role in cancer development and progression and represents an important target for anticancer drug discovery. Simultaneous targeting of components of this pathway may therefore represent a promising strategy for cancer treatment. A quantitative structure-activity relationship (QSAR) model was developed using multiple linear regression (MLR). The QSAR model showed satisfactory predictive performance based on complementary internal and external validation metrics. The selected molecular descriptors were used to guide the structural modification of substituents, resulting in higher predicted activity. Accordingly, ten new molecules were designed through strategic substituent modifications. Synthetic routes for these compounds were also proposed based on reported literature procedures. Molecular docking, molecular dynamics (MD) simulations, and Petra, Osiris, and Molinspiration (POM) analyses supported the prioritization of Pred 9 and Pred 10 as computationally designed candidates for further investigation. In silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions indicated that Pred 9 and Pred 10 may exhibit favorable pharmacokinetic properties. Overall, the results support the consideration of these compounds for experimental synthesis and biological evaluation. However, Pred 9 and Pred 10 have not yet been synthesized or experimentally evaluated for MEK1 inhibition or anticancer activity.
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BibTeX
@article{errajy2026silico,
title = {{In silico design of novel indolinone-based anticancer agents and proposal of synthetic routes.}},
author = {Mohammed Er-Rajy and Mohamed El Fadili and Hanane Etabti and Arzine Aziz and Fatimazohra Lenda and Somdutt Mujwar and Samir Chtita and Abdelouahid Samadi and Menana Elhallaoui},
journal = {Frontiers in bioinformatics},
year = {2026},
month = oct,
doi = {10.3389/fbinf.2026.1964610},
url = {https://europepmc.org/article/MED/42953008},
note = {CC BY},
}
RIS
TY - JOUR
TI - In silico design of novel indolinone-based anticancer agents and proposal of synthetic routes.
AU - Mohammed Er-Rajy
AU - Mohamed El Fadili
AU - Hanane Etabti
AU - Arzine Aziz
AU - Fatimazohra Lenda
AU - Somdutt Mujwar
AU - Samir Chtita
AU - Abdelouahid Samadi
AU - Menana Elhallaoui
PY - 2026
DA - 2026/10/14
JO - Frontiers in bioinformatics
DO - 10.3389/fbinf.2026.1964610
UR - https://europepmc.org/article/MED/42953008
AB - The RAF-MEK-ERK signaling pathway plays a central role in cancer development and progression and represents an important target for anticancer drug discovery. Simultaneous targeting of components of this pathway may therefore represent a promising strategy for cancer treatment. A quantitative structure-activity relationship (QSAR) model was developed using multiple linear regression (MLR). The QSAR model showed satisfactory predictive performance based on complementary internal and external validation metrics. The selected molecular descriptors were used to guide the structural modification of substituents, resulting in higher predicted activity. Accordingly, ten new molecules were designed through strategic substituent modifications. Synthetic routes for these compounds were also proposed based on reported literature procedures. Molecular docking, molecular dynamics (MD) simulations, and Petra, Osiris, and Molinspiration (POM) analyses supported the prioritization of Pred 9 and Pred 10 as computationally designed candidates for further investigation. In silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions indicated that Pred 9 and Pred 10 may exhibit favorable pharmacokinetic properties. Overall, the results support the consideration of these compounds for experimental synthesis and biological evaluation. However, Pred 9 and Pred 10 have not yet been synthesized or experimentally evaluated for MEK1 inhibition or anticancer activity.
SN - 2673-7647
ER -