Research Information System
The 10th International Mediterranean Symposium on Medicinal and Aromatic Plants, İstanbul, Turkey, 25 - 27 April 2024, vol.1, no.1, pp.138
Selaginella, a diverse genus with a rich medicinal history, has been used in traditional remedies, including for cancer treatment [1]. Based on our previous research, we have identified the potential of some of the Selagibenzophenone B (SB) analogs to selectively target prostate cancer cells [2]. Through in silico studies, we have designed novel SB derivatives and found that they reveal PARP-1 as a promising target. In the case of castration-resistant prostate cancer (CRPC), a type of cancer that is notoriously resistant to conventional treatments [3], there is hope in targeted therapies that focus on inhibiting PARP-1 [4]–[6]. Our objective is to discover compounds that can effectively inhibit PARP-1. The cytotoxic impact of SB derivatives on CRPC and human normal prostate cells was assessed through the SRB assay. Wound healing and colony formation assays were conducted to evaluate the cell migration and invasion capacities of the lead compounds (with IC50 ≤ 10 µM and SI >2). Gene expressions at the mRNA level were examined via Q-PCR to comprehend the type of cell death induced by the derivatives. The potential of these compounds to bind PARP-1 for inhibition was determined by molecular docking analyses. Molecular dynamics simulations were employed to determine the binding free energy of protein-ligand complexes. The lead SB derivatives exhibited selective inhibition of cell survival, migration, and colony formation in prostate cancer cell lines compared to healthy cells. In addition, molecular docking and molecular dynamics studies revealed a high binding affinity between these compounds and PARP-1. The lead compounds were also found to be druggable based on Lipinski and Veber filter assessments. In essence, SBs have the capacity to function as inhibitors of PARP1 and could be progressed as promising candidates for anticancer treatment. Our team is currently conducting further analyses to confirm their effectiveness and understand their mechanism of action.
Key Words: Castration-resistant prostate cancer, PARP-1, Selagibenzophenone
Acknowledgement: Some of the computational analyses were conducted using resources from TUBITAK ULAKBIM, the High Performance
and Grid Computing Center (TRUBA). This study received partial funding from the Health Institutes of Türkiye (TUSEB) under project
number B-22842, as well as from the Canakkale Onsekiz Mart University BAP unit under project number FYL-2023-4406. The authors express
their gratitude to TUBITAK, TUSEB, and ÇOMUBAP for their financial support.
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