Study of the Anticancer and Antimicrobial Biological Activity of a New Series of Thiohydantoin Derivatives
Keywords:Anti-bacterial activity, Antifungal activity, Isothiocyanate, Prostate cancer, Thiohydantoin
Recently, some prostate cancer patients have acquired resistance to the second -generation drugs (anzalutamide and apalutamide) prescribed for the treatment of this disease due to the emergence of the F876L mutation, which represents a challenge to modern medicine. In this study, a new series of 2-thiohydantoin derivatives were prepared through the reaction of different derivatives of maleimide (1c-4c) with isothiocyanate derivatives. The prepared compounds were diagnosed using FT-IR,1H-NMR ,13C-NMR, Mass spectra. The prepared series compounds has been studied against prostate cancer cells. The MTT assay was used to determine the activity of the prepared compounds against prostate cancer cells. The data indicated, depending on the IC50 values, that some of the prepared compounds have anti-prostate cancer activity. The results indicate that compounds 1d and 2d have good anti-prostate cancer activity compared to the rest of the compounds. The prepared series of compounds were also studied against selected types of bacteria and fungi, as the results showed that some of the compounds in the series had anti-bacterial and anti-fungal activity.
Published Online First 20/5/2023
Baeyer A. Vorläufige Notiz über das Hydantoïn. Liebigs Ann Chem. 1861;117(2):178–180. https://doi.org/10.1002/jlac.18611170204.
Klason P. An apparatus for preparing chloride. P Chem Ztg. 1890; 14: 543.
Han X , Wang C, Qin C, Xiang W, Fernandez-Salas E, Yang, C Y, et al. Discovery of ARD-69 as a highly potent proteolysis targeting chimera (PROTAC) degrader of androgen receptor (AR) for the treatment of prostate cancer. J. Med. Chem. 2019; 62(2): 941-964.https://doi.org/10.1021/acs.jmedchem.8b01631 .
Khodair A I, Bakare S B, Awad M K, Nafie M S. Design, synthesis, DFT, molecular modelling studies and biological evaluation of novel 3-substituted (E)-5-(arylidene)-1-methyl-2-thioxoimidazolidin-4-ones with potent cytotoxic activities against breast MCF-7, liver HepG2, and lung A549. J Mol Struct. 2021; 1229: 129805.https://doi.org/10.1016/j.molstruc.2020.129805.
Xu X , Ge R , Li L, Wang J , Lu X, Xue S. Exploring the tetrahydroisoquinoline thiohydantoin scaffold blockade the androgen receptor as potent anti-prostate cancer agents. Eur J Med Chem. 2018; 143: 1325-1344. https://doi.org/10.1016/j.ejmech.2017.10.031.
AbdulJabar L A, Al-Shawi A A A , Mutlaq D Z. Anti-liver and anti-breast cancer activities of 2-thioxo-4- imidazolidinone derivatives. Med Chem Res. 2021; 30: 1943–1953. https://doi.org/10.1007/s00044-021-02769-8.
Wang A, Wang Y, Meng X , Yang Y. Design, synthesis and biological evaluation of novel thiohydantoin derivatives as potent androgen receptor antagonists for the treatment of prostate cancer. Bioorg Med Chem. 2021; 31: 115953. doi: https://doi.org/10.1016/j.bmc.2020.115953.
Elbadawi M M, Khodair A I, Awad M K, Kassab S E, Elsaady M T, Abdellatif K R. Design, synthesis and biological evaluation of novel thiohydantoin derivatives as antiproliferative agents: A combined experimental and theoretical assessments. J Mol Struct. 2022; 1249: 131574. https://doi.org/10.1016/j.molstruc.2021.131574.
Camargo P G, Bortoleti B T D S , Fabris M, Gonçalves M D , Tomiotto-Pellissier F , Costa I N, et al. Thiohydantoins as anti-leishmanial agents: n vitro biological evaluation and multi-target investigation by molecular docking studies. J Biomol Struct Dyn. 2022; 40(7): 3213-3222. https://doi.org/10.1080/07391102.2020.1845979.
Chen L, Hao Y, Song H, Liu Y, Li Y, Zhang J, Wang Q. Design, synthesis, characterization, and biological activities of novel spirooxindole analogues containing hydantoin, thiohydantoin, urea, and thiourea moieties. J Agric Food Chem. 2020; 68(39): 10618-10625. https://doi.org/10.1021/acs.jafc.0c04488 .
Peng X R, Zhang R R, Liu J H, Li Z R, Zhou L, Qiu M H. Lepithiohydimerins A—D: Four Pairs of Neuroprotective Thiohydantoin Dimers Bearing a Disulfide Bond from Maca (Lepidium meyenii Walp.). Chin J Chem. 2021; 39(10): 2738-2744. https://doi.org/10.1002/cjoc.202100353 .
Tejchman W, Orwat B, Korona-Głowniak I, Barbasz A, Kownacki I, Latacz G, et al. Highly efficient microwave synthesis of rhodanine and 2-thiohydantoin derivatives and determination of relationships between their chemical structures and antibacterial activity. RSC Adv. 2019;9(67): 39367-39380. https://doi.org/10.1039/C9RA08690K .
De Carvalho P G , Ribeiro J M , Garbin R P B , Nakazato G , Yamada Ogatta S F , de Fátima. Synthesis and antimicrobial activity of thiohydantoins obtained from L-amino acids. Lett Drug Des Discov. 2020; 17(1): 94-102. https://doi.org/10.2174/1570180816666181212153011.
Mutlaq D Z, Al-Shawi A A, AbdulJabar L A. Antioxidant and antimicrobial activities of some novel 2-thiohydantoin derivatives. Egypt. J. Chem. 2021; 64(3): 1315-1321. https://doi.org/10.21608/EJCHEM.2020.47419.2963 .
Huang Y, Guo Z, Song H, Liu Y, Wang L, Wang Q. Design, synthesis, and biological activity of β-carboline analogues containing hydantoin, thiohydantoin, and urea moieties. J Agric Food Chem. 2018; 66(31): 8253-8261. https://doi.org/10.1021/acs.jafc.8b03087.
Lee T H, Khan Z, Kim S Y , Lee K R. Thiohydantoin and hydantoin derivatives from the roots of Armoracia rusticana and their neurotrophic and anti-neuroinflammatory activities. J Nat Prod. 2019; 82(11): 3020-3024. https://doi.org/10.1021/acs.jnatprod.9b00527.
Sawyers C L , Jung M E, Chen C D , Ouk S, Welsbie D, Tran C, et al. Diarylhydantoin Compounds. PCT Int. Patent Appl. WO2006/124118, November 23, (2006).
Jung M E , Ouk S , Yoo D, Sawyers C L, Chen C, Tran C, et al. StructureActivity Relationship for Thiohydantoin Androgen Receptor Antagonists for CastrationResistant Prostate Cancer (CRPC). J Med. Chem. 2010; 53: 2779-2796. https://doi.org/10.1021/jm901488g .
Brave M, Weinstock C, Brewer J R, Chi D C, Suzman D L, Cheng J, et al. An FDA Review of Drug Development in Nonmetastatic Castration-resistant Prostate CancerFDA Review: Drug Development in nmCRPC. Clin Cancer Res. 2020; 26(18): 4717-4722. https://doi.org/10.1158/1078-0432.CCR-19-3835.
Korpal M, Korn J M, Gao X, Rakiec D P, Ruddy D A, Doshi S, et al. An F876L mutation in androgen receptor confers genetic and phenotypic resistance to MDV3100 (enzalutamide). Cancer Discov. 2013; 3(9): 1030-1043. https://doi.org/10.1158/2159-8290.CD-13-0142
Joseph J D, Lu N, Qian J , Sensintaffar J , Shao G , Brigham D , et al. A Clinically Relevant Androgen Receptor Mutation Confers Resistance to Second-Generation Antiandrogens Enzalutamide and ARN-509AR F876L Confers Enzalutamide and ARN-509 Resistance. Cancer Discov. 2013; 3(9): 1020-1029.; https://doi.org/10.1158/2159-8290.CD-13-0226.
Meerloo J V, Kaspers G J, Cloos J. Cell sensitivity assays: the MTT assay. Cancer cell culture. 2011; 731:237. https://doi.org/10.1007/978-1-61779-080-5_20 .
Bouzroura S, Hammal L, Nedjar‐ Kolli B, Balegroune F, Hamadene M, Poulain S. Synth. Commun. 2008; 38: 448-455. https://doi.org/10.1080/00397910701316987 .
Troin Y, Bentarzi Y, Nedjar-Kolli B, Plas A, Chalard P. Arkivoc. 2010; 328-337. http://dx.doi.org/10.3998/ark.5550190.0011.a27.
Smania Jr A , Monache F D , Smania E D F A , Cuneo R S. Antibacterial activity of steroidal compounds isolated from Ganoderma applanatum (Pers.) Pat.(Aphyllophoromycetideae) fruit body. Int J Med Mushrooms. 1999; 1(4):325-3330. https://doi.org/10.1615/IntJMedMushr.v1.i4.40 .
Thangavelu R, Devi P G, Gopi M, Mustaffa M M .Management of Eumusae leaf spot disease of banana caused by Mycosphaerella eumusae with Zimmu (Allium sativum× Allium cepa) leaf extract. Crop Prot. 2013;46: 100-105. https://doi.org/10.1016/j.cropro.2012.12.022.
Ali Z Z M, Abdulla A M. Synthesis and Antimicrobial Schreening of New 4, 5, 6, 7-Tatra Hydro Benzo Thiophene Derivatives. Baghdad Sci J. 2019; 16(1): 68-77. http://dx.doi.org/10.21123/bsj.2019.16.1.0068.
Alsahib S A. Characterization and Biological Activity of Some New Derivatives Derived from Sulfamethoxazole Compound. Baghdad Sci J. 2020; 17(2): 471-480. DOI: http://dx.doi.org/10.21123/bsj.2020.17.2.0471.
Wu Y, Ding X , Xu S , Yang Y , Zhang X , Wang C , et al. Design and synthesis of biaryloxazolidinone derivatives containing a rhodanine or thiohydantoin moiety as novel antibacterial agents against Gram-positive bacteria. Bioorg Med Chem Lett. 2019; 29(3): 496-502. https://doi.org/10.1016/j.bmcl.2018.12.012 .
AbdulJabar L A, Mutlaqa D Z, Al-Shawia A A A. Sythesis of Novel 2-Thioxo-4-Imidazolidinone Derivatives and Evaluate Their Antibacterial, And Antifungal Activities. Egypt J Chem. 2021:64; 3059 - 3067. https://doi.org/10.21608/EJCHEM.2021.66960.3442 .
Kania A , Tejchman W, Pawlak A M , Mokrzyński K , Różanowski B , Musielak B M , et al. Preliminary Studies of Antimicrobial Activity of New Synthesized Hybrids of 2-Thiohydantoin and 2-Quinolone Derivatives Activated with Blue Light. Molecules. 2022; 27(3): 1069. https://doi.org/10.3390/molecules27031069.
Ghasempour L, Asghari S, Tajbakhsh M, Mohseni M. One‐pot synthesis of new hydantoin (thiohydantoin) derivatives and evaluation of their antibacterial and antioxidant activities. J Heterocycl Chem. 2020; 57(12): 4136-4148. https://doi.org/10.1002/jhet.4120 .
Mollanejad K, Asghari S, Jadidi K. Diastereoselective synthesis of pyrrolo [1, 2‐c] imidazoles using chiral thiohydantoins, malononitrile, and aldehydes and evaluation of their antioxidant and antibacterial activities. J Heterocycl Chem. 2020; 57(2): 556-564. https://doi.org/10.1002/jhet.3762.
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