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Radiolabeling and In-Silico Study of 131I-(4-fluorobenzoyl-3-methylthiourea) as Radiopharmaceuticals for Breast Cancer Theranostics

Febby Pratama, Ruswanto Ruswanto, Tita Nofianti, Anindita Tri Kusuma Pratita, Isti Daruwati, Veronika Yulianti Susilo, Holis Abdul Holik

Abstract


The chemicals produced from thiourea are actively being studied as anticancer possibilities. In complexes with radionuclides like Iodine-131, the 1-(4-Fluorobenzoyl)-3-methyl thiourea is a promising ligand for theragnostic applications. This study aimed to label 1-(4-fluorobenzoyl-3-methylthiourea) with iodine-131 and observe its interaction with breast cancer receptors. The radiolabeling of 131I-(4-fluorobenzoyl-3-methylthiourea) uses the radioiodination method with Chloramine-T, and an in-silico investigation of breast cancer receptors was conducted. According to the results of molecular docking using AutoDockTools, this radiopharmaceutical molecule has the best activity on the HER2 receptor (PDB ID: 3PP0) compared to the native ligand and control positive, with a binding affinity of -6.13 kcal/mol and a Ki value of 32.05 mM. According to the molecular dynamics data using Desmond, the radiopharmaceutical molecule 131I-(4-Fluorobenzoyl-3-methylthiourea) displays good stability starting from the 50ns range. The indirect radioiodination method has successfully labeled 1-(4-Fluorobenzoyl-3-methylthiourea) with iodine-131.

Keywords


HER2; iodine-131; molecular dynamics; radioiodination; thiourea

References


Sriyani ME, Widyasari BEM, Febriyanti CH, et al. Karakteristik Fisikokimia Senyawa Kuersetin Bertanda Radioaktif Iodium-131. gnd. 2020;23(1):9. doi:10.17146/gnd.2020.23.1.5515

Ersahin D, Doddamane I, Cheng D. Targeted Radionuclide Therapy. Cancers. 2011;3(4):3838-3855. doi:10.3390/cancers3043838

Petrov SA, Yusubov MS, Beloglazkina EK, Nenajdenko VG. Synthesis of Radioiodinated Compounds. Classical Approaches and Achievements of Recent Years. IJMS. 2022;23(22):13789. doi:10.3390/ijms232213789

Yeong CH, Cheng M hua, Ng KH. Therapeutic radionuclides in nuclear medicine: current and future prospects. J Zhejiang Univ Sci B. 2014;15(10):845-863. doi:10.1631/jzus.B1400131

Ílem-Özdemir D. Estimating Binding Capability of Radiopharmaceuticals by Cell Culture Studies. Int J Med Nano Res. 2016;3(1). doi:10.23937/2378-3664/1410014

Daruwati I, Anggraini Y, Wangsaatmadja AH. Labeling of Piperine with Iodine-131 as Radiotracer in the Development of Cancer Drugs from Indonesia’s Natural Products. IJPST. 2019;1(3):18. doi:10.24198/ijpst.v1i3.21031

Ruswanto R, Nugraha A. Sintesis Senyawa 1-(4-Heptilbenzoil-3-metiltiourea) dan Uji Sitotoksisitas Terhadap Sel T47D Sebagai Kandidat Antikanker. j. 2015;14(1):145. doi:10.36465/jkbth.v14i1.123

Canudo-Barreras G, Ortego L, Izaga A, Marzo I, Herrera RP, Gimeno MC. Synthesis of New Thiourea-Metal Complexes with Promising Anticancer Properties. Molecules. 2021;26(22):6891. doi:10.3390/molecules26226891

Huang RZ, Zhang B, Huang XC, et al. Synthesis and biological evaluation of terminal functionalized thiourea-containing dipeptides as antitumor agents. RSC Adv. 2017;7(15):8866-8878. doi:10.1039/C6RA25590F

Parmar DR, Soni JY, Guduru R, et al. Discovery of new anticancer thiourea-azetidine hybrids: design, synthesis, in vitro antiproliferative, SAR, in silico molecular docking against VEGFR-2, ADMET, toxicity, and DFT studies. Bioorganic Chemistry. 2021;115:105206. doi:10.1016/j.bioorg.2021.105206

Pingaew R, Prachayasittikul V, Anuwongcharoen N, Prachayasittikul S, Ruchirawat S, Prachayasittikul V. Synthesis and molecular docking of N,N′-disubstituted thiourea derivatives as novel aromatase inhibitors. Bioorganic Chemistry. 2018;79:171-178. doi:10.1016/j.bioorg.2018.05.002

Ruswanto R, Mardianingrum R, Lestari T, Nofianti T, Tuslinah L, Nurmalik D. In silico study of the active compounds in bitter melon (Momordica charantia L) as antidiabetic medication. Pharmaciana. 2018;8(2):194. doi:10.12928/pharmaciana.v8i2.8993

Ruswanto, Miftah AM, Tjahjono DH, Siswandono. Synthesis and in vitro Cytotoxicity of 1-Benzoyl-3-methyl Thiourea Derivatives. Procedia Chemistry. 2015;17:157-161. doi:10.1016/j.proche.2015.12.105

Ruswanto R, Miftah AM, Tjahjono DH, Siswandono. In silico study of 1-benzoyl-3-methylthiourea derivatives activity as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor candidates. Chemical Data Collections. 2021;34:100741. doi:10.1016/j.cdc.2021.100741

Renadi S, Pratita ATK, Mardianingrum R, Ruswanto R. The Potency of Alkaloid Derivates as Anti-Breast Cancer Candidates: In Silico Study. Valensi. 2023;9(1):89-108. doi:10.15408/jkv.v9i1.31481

Mardianingrum R, Ruswanto R, Agustien GS, Nuraisah A. The Active Compound of Bangle Essential Oil as Cyclooxygenase-2 (Cox-2) Inhibitor: In Silico Approach. Valensi. 2020;6(2):156-168. doi:10.15408/jkv.v6i2.16943

Ruswanto R, Nofianti T, Mardianingrum R, Lestari T. Desain dan Studi In Silico Senyawa Turunan Kuwanon-H sebagai Kandidat Obat Anti-HIV. JKV. 2018;4(1):57-66. doi:10.15408/jkv.v4i1.6867

Ruswanto R, Mardianingrum R, Nofianti T, Fizriani R, Siswandono S. Computational Study of Bis-(1-(Benzoyl)-3-Methyl Thiourea) Platinum (II) Complex Derivatives as Anticancer Candidates. AABC. 2023;Volume 16:15-36. doi:10.2147/AABC.S392068

Septian AD, Wardani GA, Mardianingrum R, Ruswanto R. The Virtual Screening of Flavonoid Derivatives on Progesterone, Estrogen, and HER-2 Receptor for Breast Cancer Treatment Candidate. Valensi. 2023;9(1):163-182. doi:10.15408/jkv.v9i1.31482

Kumar S, Sharma PP, Shankar U, et al. Discovery of New Hydroxyethylamine Analogs against 3CL pro Protein Target of SARS-CoV-2: Molecular Docking, Molecular Dynamics Simulation, and Structure–Activity Relationship Studies. J Chem Inf Model. 2020;60(12):5754-5770. doi:10.1021/acs.jcim.0c00326

Daruwati I, Gwiharto AK, Kurniawan A, et al. Synthesis, stability, and cellular uptake of 131I-estradiol against MCF7 and T-47D human cell lines as a radioligand for binding assay. Heliyon. 2021;7(11):e08438. doi:10.1016/j.heliyon.2021.e08438

Muttaqin FZ. Studi Molecular Docking, Molecular Dynamic, dan Prediksi Toksisitas Senyawa Turunan Alkaloid Naftiridin Sebagai Inhibitor Protein Kasein Kinase 2-α Pada Kanker Leukimia. PHARMACOSCRIPT. 2019;2(1):49-64. doi:10.36423/pharmacoscript.v2i1.241

Ruswanto R, Rahayuningsih N, Hidayati NLD, Nuryani GS, Mardianingrum R. Uji In Vitro dan Studi In Silico Senyawa Turunan N’-Benzoylisonicotinohydrazide sebagai Kandidat Antituberkulosis. 2019;17.

Vinsiah R, Fadhillah F. Studi Ikatan Hidrogen Sistem Metanol-Metanol dan Etanol-Etanol dengan Metode Molekular Dinamik. sainmatika. 2018;15(1):14. doi:10.31851/sainmatika.v15i1.1739

Pires DEV, Blundell TL, Ascher DB. pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures. J Med Chem. 2015;58(9):4066-4072. doi:10.1021/acs.jmedchem.5b00104

Prayoga H, Yulianti Y, Riyanto A. Analisis Dinamika Molekul Protein Lysozyme Putih Telur dengan Model Potensial Lennard-Jones Menggunakan Aplikasi GROMACS. JTAF. 2018;6(2):239-248. doi:10.23960/jtaf.v6i2.1849

Hollup SM, Fuglebakk E, Taylor WR, Reuter N. Exploring the factors determining the dynamics of different protein folds. Protein Science. 2011;20(1):197-209. doi:10.1002/pro.558

Yin C, Feng L, Zhang N, Cheng Y. How environmental factors affect the structural properties and biofunctions of keratin: A molecular dynamics study. Materials Today Communications. 2023;34:105254. doi:10.1016/j.mtcomm.2022.105254

Dubost E, McErlain H, Babin V, Sutherland A, Cailly T. Recent Advances in Synthetic Methods for Radioiodination. J Org Chem. 2020;85(13):8300-8310. doi:10.1021/acs.joc.0c00644

Kumar K, Ghosh A. Radiochemistry, Production Processes, Labeling Methods, and ImmunoPET Imaging Pharmaceuticals of Iodine-124. Molecules. 2021;26(2):414. doi:10.3390/molecules26020414

Saha GB. Fundamentals of Nuclear Pharmacy. Springer International Publishing; 2018. doi:10.1007/978-3-319-57580-3

Vallabhajosula S, Killeen RP, Osborne JR. Altered Biodistribution of Radiopharmaceuticals: Role of Radiochemical/Pharmaceutical Purity, Physiological, and Pharmacologic Factors. Seminars in Nuclear Medicine. 2010;40(4):220-241. doi:10.1053/j.semnuclmed.2010.02.004


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DOI: 10.15408/jkv.v10i1.34258

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Copyright (c) 2024 Ruswanto Ruswanto, Febby Pratama, Tita Nofianti, Anindita Tri Kusuma Pratita, Isti Daruwati, Veronika Yulianti Susilo, Holis Abdul Holik

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