دراسة الفعالية البايولوجية المضادة للسرطان والميكروبات لسلسلة جديدة من مشتقات الثيوهيدانتوين
محتوى المقالة الرئيسي
الملخص
في الأونة الأخيرة اكتسب بعض مرضى سرطان البروستات مقاومة أدوية الجيل الثاني (أنزالوتاميد وابالوتاميد) المقررة لعلاج هذا المرض والسبب يعود الى ظهور الطفرةF876L والتي تمثل تحديا للطب الحديث .في هذه الدراسة تم تحضير سلسلة جديدة من مشتقات 2-ثايوهيدانتوين وذلك بوساطة تفاعل مشتقات الماليميايد (1c-4c) مع مشتقات الايزوثايوسيانات.
تم تشخيص المركبات المحضرة باستخدام تم دراسة سلسلة المركبات المحضرة ضد خطوط خلايا سرطان البروستات . تم استخدام فحص MTT لتحديد نشاط المركبات المحضرة ضد خطوط خلايا سرطان البروستات أذ أشارت البيانات وبالأعتماد على قيم IC50 أن بعض المركبات المحضرة لها نشاط مضاد لخطوط خلايا سرطان البروستات . تشير النتائج إلى أن المركبين1d و2d لهما نشاط جيد ضد خطوط خلايا سرطان البروستات مقارنة مع بقية مركبات السلسلة قيد الدراسة . كما تمت دراسة سلسلة المركبات المحضرة ضد أنواع مختارة من البكتيريا والفطريات، حيث أظهرت النتائج أن بعض مركبات السلسلة المحضرة لها نشاط مضاد للبكتيريا والفطريات قيد الدراسة .
Received 18/10/2022,
Revised 4/2/2023,
Accepted 5/2/2023,
Published Online First 20/5/2023
تفاصيل المقالة
هذا العمل مرخص بموجب Creative Commons Attribution 4.0 International License.
كيفية الاقتباس
المراجع
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.