Computational modeling of cyanobacterial phytoconstituents against toll-like receptors of skin cancer

Abstract

Melanoma is an extremely dangerous disease. The diagnosis and treatment of it may be difficult because of its diversity and complexity. More than 90% of the marine biomass (microflora and microalgae) constitutes the natural biodiversity reserves. TLR-related research developments indicate possible cancer therapeutic possibilities. In addition to its significant function in innate immunity, TLR activation is connected to the start of pyroptosis, apoptosis, or autophagy in malignance cells. For these reasons, TLR agonists are appealing candidates for the production of cancer medications. From the web databases, the ternary structures of the receptors (TLR3 and TLR4) and ligands are extracted. Sixty-nine compounds were subjected to a drug likeness filter, but only twenty-two were screened further for evaluating ADMET criteria, in which only seven compounds satisfied the pharmacological properties. These compounds are further analyzed for docking parameters against TLRs (TLR3 and TLR4) and molecular simulation investigation of the best cluster to evaluate the complex stability. Molecular docking methodology discovered that Scytonmein has a significant binding potential energy of −5.21 and −7.92 kcal/mol against TLR3 and TLR4, respectively, in comparison to the redock co-crystal structure (−3.98 and −4.30 kcal/mol, respectively). The simulation analysis demonstrates the significant stability of the Scytonemin and TLR4 complexes in terms of average RMSD and RMSF compared to the redock complex, while criteria like solvent-accessible surface area (SASA), gyration (Rg) and hydrogen bonding have further supported the significant interaction and stability of the conformations.

Communicated by Ramaswamy H. Sarma

Keywords:

• Melanoma
• toll-like receptors
• cyanobacteria
• drug likeness
• docking
• simulation

Acknowledgments

The authors acknowledge the Office of Doctoral Studies and Research for critically reviewing the manuscript and providing the manuscript number (IU/R&D/2022-MCN0001705). The authors thank Scientific Research Deanship, University of Ha’il, Saudi Arabia for providing financial assistance.

Authors’ contributions

IZA conceived the idea; EK and SK performed the experiments. MK and ML analyzed data and drafted he manuscript. NZAB, HAAM, KPand IZA reviewed and edited the manuscript. EK, SK and IZA contributed to study design. All authors read and approved the final manuscript.

Availability of data and materials

Data can be made available upon request.

Disclosure statement

The authors declare no conflict of interest, financial or otherwise.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by Scientific Research Deanship at University of Ha’il, Saudi Arabia through project number RG-21110.