Unveiling the multitargeted potency of Sodium Danshensu against cervical cancer: a multitargeted docking-based, structural fingerprinting and molecular dynamics simulation study

• Published in: Journal of biomolecular structure & dynamics Vol. 42; no. 16; pp. 8268 - 8280
• Main Authors: Alghamdi, Saad, Baeissa, Hanadi M., Azhar Kamal, Mohammad, Rafeeq, Misbahuddin M., Al Zahrani, Abdullah, Maslum, Ali Ahmed, Hakeem, Israa J., Alazragi, Reem S., Alam, Qamre
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01-11-2024
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Binding Sites; Cervical cancer; docking-based interaction fingerprints; FDA-approved drugs; Female; Humans; Lactates - chemistry; Lactates - pharmacology; Ligands; Molecular Docking Simulation; Molecular Dynamics Simulation; pharmacokinetics; Protein Binding; Structure-Activity Relationship; Uterine Cervical Neoplasms - drug therapy; FDA-approved drugs; docking-based interaction fingerprints; pharmacokinetics; Cervical cancer; molecular dynamics simulation
• ISSN: 0739-1102; 1538-0254; 1538-0254
• DOI: 10.1080/07391102.2023.2248260

Cervical Cancer (CC) is one of the most common types of cancer in women worldwide, with a significant number of deaths reported yearly. Despite the various treatment options available, the high mortality rate associated with CC highlights the need to develop new and effective therapeutic agents. In this study, we have screened the complete prepared FDA library against the Mitotic kinesin-like protein 1, Cyclin B1, DNA polymerase, and MCM10-ID using three glide-based molecular docking algorithms: HTVS, SP and XP to produce a robust calculation. All four proteins are crucial proteins that actively participate in CC development, and inhibiting them together can be a game-changer step for multitargeted drug designing. Our multitargeted screening identified Sodium (Na) Danshensu, a natural FDA-approved phenolic compound of caffeic acid derivatives isolated from Salvia miltiorrhiza. The docking score ranges from −5.892 to −13.103 Kcal/mol, and the screening study was evaluated with the pharmacokinetics and interaction fingerprinting to identify the pattern of interactions that revealed that the compound has bound to the best site it can be fitted to where maximum bonds were created to make the complex stable. The molecular dynamics simulations for 100 ns were then extended to validate the stability of the protein-ligand complexes. The results provide insight into the repurposing, and Na-danshensu exhibited strong binding affinity and stable complex formation with the target proteins, indicating its potential as a multitargeted drug against CC.
Communicated by Ramaswamy H. Sarma