Investigating the anticancer potential of phytochemicals from the mangrove Rhizophora mucronata as inhibitors of lung cancer-associated proteins: Insights from multiscale computational and in silico analyses
8 affiliations
- 1Department of Medical Physics, College of Applied Medical Sciences, University of Kerbala, Karbala, Iraq
- 2Ministry of Education, General Directorate of Education in Kerbala, Iraq
- 3Department of Agroforestry and Environmental Science, Sylhet Agricultural University, Sylhet, Bangladesh
- 4College of Agricultural Sciences, IUBAT—International University of Business Agriculture and Technology, Dhaka, Bangladesh
- 5Department of General Medicine, Saveetha Institute of Medical and Technical Sciences in Saveetha Medical College and Hospital, Chennai, India
- 6College of Arts and Sciences, Department of Chemistry, IUBAT—International University of Business Agriculture and Technology, Dhaka, Bangladesh
- 7Department of Biology, College of Science, University of Babylon, Babylon, Iraq
- 8Department of Environmental Health, College of Applied Medical Sciences, University of Kerbala, Karbala, Iraq
Abstract
Lung cancer remains the leading cause of cancer-related mortality worldwide, with a five-year survival rate of approximately 20–25% despite advances in targeted therapy and immunotherapy. There is a continuous need for novel, low-toxicity compounds capable of modulating key oncogenic pathways in non-small cell lung cancer (NSCLC). Mangrove ecosystems are rich reservoirs of bioactive phytochemicals, yet the inhibitory potential of compounds from Rhizophora mucronata against validated lung cancer-associated proteins has not been systematically explored using multi-scale computational approaches. This study employed an integrated computational pipeline to evaluate 14 phytochemicals from R. mucronata. Density Functional Theory (DFT) calculations at the B3LYP/6-31G* level were performed to characterize electronic properties of the ligands. Molecular docking studies were conducted using both AutoDock Vina (PyRx) and Schrödinger Glide against the Keap1 Kelch domain (PDB 1X2J) and the YEATS2 YEATS domain (PDB 5XNV). Top-ranked complexes were subjected to 100-ns molecular dynamics (MD) simulations in Desmond, and pharmacokinetic and toxicity profiles were predicted using SwissADME and pkCSM. Among the screened compounds, ligand L10 (cyclohexane-1,2,3,4,5,6-hexaol) exhibited the smallest HOMO–LUMO energy gap (0.36 eV), favorable binding affinities (Glide score of –7.789 kcal/mol against 1X2J), multiple hydrogen-bonding interactions, and stable complex behavior during MD simulations (Cα RMSD < 3 Å). Several other ligands (L02, L05, and L07) also displayed promising profiles. Most compounds complied with Lipinski’s rule of five and showed acceptable predicted ADMET properties. These preliminary findings suggest that Rhizophora mucronate -derived phytochemicals, particularly L10, are promising candidates for further experimental evaluation as modulators of Keap1 and YEATS2 in lung cancer. This study provides a computational framework for prioritizing natural product leads from mangrove species for subsequent in vitro and in vivo validation.
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BibTeX
@article{mahdi2026investigating,
title = {{Investigating the anticancer potential of phytochemicals from the mangrove Rhizophora mucronata as inhibitors of lung cancer-associated proteins: Insights from multiscale computational and in silico analyses}},
author = {Zena Abdul-Ameer Mahdi and Batool Shakir Abed AlmjalawI and Mollah Naimuzzaman and Md Mahabub Hasan and Ajoy Kumer and Farah Tareq Al-Alaq and Hussein O.M. Al-Dahmoshi and Faizur Rahman and Md. Fayez Al-Hakim Khan and Noor S.K. Al-Khafaji and Sarah Alwan Malik Al-Yasiri},
journal = {PLOS One},
year = {2026},
month = oct,
doi = {10.1371/journal.pone.0359525},
url = {https://doi.org/10.1371/journal.pone.0359525},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Investigating the anticancer potential of phytochemicals from the mangrove Rhizophora mucronata as inhibitors of lung cancer-associated proteins: Insights from multiscale computational and in silico analyses
AU - Zena Abdul-Ameer Mahdi
AU - Batool Shakir Abed AlmjalawI
AU - Mollah Naimuzzaman
AU - Md Mahabub Hasan
AU - Ajoy Kumer
AU - Farah Tareq Al-Alaq
AU - Hussein O.M. Al-Dahmoshi
AU - Faizur Rahman
AU - Md. Fayez Al-Hakim Khan
AU - Noor S.K. Al-Khafaji
AU - Sarah Alwan Malik Al-Yasiri
PY - 2026
DA - 2026/10/07
JO - PLOS One
DO - 10.1371/journal.pone.0359525
UR - https://doi.org/10.1371/journal.pone.0359525
AB - Lung cancer remains the leading cause of cancer-related mortality worldwide, with a five-year survival rate of approximately 20–25% despite advances in targeted therapy and immunotherapy. There is a continuous need for novel, low-toxicity compounds capable of modulating key oncogenic pathways in non-small cell lung cancer (NSCLC). Mangrove ecosystems are rich reservoirs of bioactive phytochemicals, yet the inhibitory potential of compounds from Rhizophora mucronata against validated lung cancer-associated proteins has not been systematically explored using multi-scale computational approaches. This study employed an integrated computational pipeline to evaluate 14 phytochemicals from R. mucronata. Density Functional Theory (DFT) calculations at the B3LYP/6-31G* level were performed to characterize electronic properties of the ligands. Molecular docking studies were conducted using both AutoDock Vina (PyRx) and Schrödinger Glide against the Keap1 Kelch domain (PDB 1X2J) and the YEATS2 YEATS domain (PDB 5XNV). Top-ranked complexes were subjected to 100-ns molecular dynamics (MD) simulations in Desmond, and pharmacokinetic and toxicity profiles were predicted using SwissADME and pkCSM. Among the screened compounds, ligand L10 (cyclohexane-1,2,3,4,5,6-hexaol) exhibited the smallest HOMO–LUMO energy gap (0.36 eV), favorable binding affinities (Glide score of –7.789 kcal/mol against 1X2J), multiple hydrogen-bonding interactions, and stable complex behavior during MD simulations (Cα RMSD < 3 Å). Several other ligands (L02, L05, and L07) also displayed promising profiles. Most compounds complied with Lipinski’s rule of five and showed acceptable predicted ADMET properties. These preliminary findings suggest that Rhizophora mucronate -derived phytochemicals, particularly L10, are promising candidates for further experimental evaluation as modulators of Keap1 and YEATS2 in lung cancer. This study provides a computational framework for prioritizing natural product leads from mangrove species for subsequent in vitro and in vivo validation.
SN - 1932-6203
ER -