UNIVERSITY OF BUCHAREST
FACULTY OF PHYSICS

Guest
2024-11-24 11:13
 HOME     CONFERENCES     SEARCH            LOGIN     NEW USER     IMAGES   


Conference: Bucharest University Faculty of Physics 2021 Meeting


Section: Biophysics; Medical Physics


Title:
Mechanism of action prediction of TPPS4 photosensitiser in melanoma treatment using molecular docking


Authors:
Ana-Maria UDREA (1), Simona STROESCU (1,2), Mihai BONI (1), Mihail Lucian PASCU (1), Angela STAICU (1)


*
Affiliation:
1) National Institute of Laser, Plasma and Radiation Physics, 409 Atomistilor str., RO-077125 Magurele, Ilfov.

2) Faculty of Biology, University of Bucharest, 36-46 M. Kogălniceanu Boulevard, 050107, Bucharest



E-mail
ana.udrea@inflpr.ro


Keywords:
Melanoma; Photodynamic therapy; TPPS4; Molecular Docking


Abstract:
Melanoma appears when the melanocytes become maligned. Usually, melanomas appear on the skin but may also occur in the brain or gastrointestinal tract. Melanoma had a bad prognostic: for the five-year relative survival rate, for patients with stage IV melanoma, is 10% [1]. Photodynamic therapy (PDT) is an alternative cancer treatment. PDT uses a light source to photoactivate a sensitiser to generate singlet oxygen. Previous studies reported that PDT had positive results in melanoma [2–4]. This study investigates 5,10,15,20-tetrakis(4-sulfonatophenyl) porphyrin (TPPS4) efficiency as a photosensitiser in melanoma treatment using Molecular Docking simulations. The photosensitiser should be close to the target since singlet oxygen has a short migration. We predicted the binding affinity of the photosensitiser to receptors that might be a target in melanoma or PDT treatment. The predictions include: Serine/threonine-protein kinase B-raf (BRAF), erythropoietin-producing hepatocellular receptor A2 (EphA2), B-cell lymphoma-extra-large (Bcl- xL), Myeloid cell leukemia 1 (Mcl-1), BID, Proaspase-3 and Procaspase-7. We obtained high biological activity (due to low free energy of binding) on all the possible targets in PDT or melanoma. The shifted position of the TPPS4 from the binding sites of the target also suggests that the photosensitiser has no effect without light exposure after administration.


References:

[1] Heistein JB, Acharya U. Malignant Melanoma. [Updated 2020 Dec 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470409/

[2] Baldea I, Filip AG.Photodynamic Therapy in Melanoma--an Update. J Physiol Pharmacol 2012, 63 (2), 109–118.

[3] Baldea I, Giurgiu L, Teacoe ID, Olteanu DE, Olteanu FC, Clichici S, Filip AG. Photodynamic Therapy in Melanoma - Where Do We Stand?, CMC 2019, 25 (40), 5540–5563. https://doi.org/10.2174/0929867325666171226115626.

[4] Agostinis P, Berg K, Cengel KA, Foster TH, et al. Photodynamic Therapy of Cancer: An Update. CA Cancer J Clin 2011, 61 (4), 250–281. https://doi.org/10.3322/caac.20114.



Acknowledgement:
This research was funded by Romanian National Authority for Scientific Research and Innovation, CNCS/CCCDI-UEFISCDI, projects PN-III-P1-1.1-PCCDI-2017-0728, PN-III-P2-2.1-PED-2019-4771, PN-III-P2-2.1-PED-2019-1264, PN-III-P2-2.1-PED-2019-5283.