Ionic Liquids Immobilized Synthesis of New Xanthenes Derivatives and their Antiproliferative, Molecular Docking, and Morphological Studies


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Аннотация

Background::Xanthenes and benzoxanthenesare are highly valuable compounds in organic chemistry and medicinal chemistry. Xanthene derivatives were found to have many applications in medicinal chemistry.

Objective::This work aims to explore the synthesis of xanthene derivatives with various substituents and find the possibility of their uses as anticancer agents.

Methods:The basic starting compound through this work was the 2,3-dihydro-1H-xanthen-1-one (3), which was synthesized from the reaction of cyclohexan-1,3-dione and 2-hydroxybenzaldehyde. Compound 3 was used to synthesize new thiophene, pyrimidine, isoxazole, and thiazole derivatives based on the xanthenes nucleus. Fused xanthene derivatives were obtained through further heterocyclization reactions. Multicomponent reactions expressed in this work were carried out in the presence of solvent catalyzed by Et3N and in solvent-free ionic liquid immobilized catalyst.

Results::Cytotoxicity for the newly synthesized compounds toward cancer cell lines was measured, and the results revealed that many compounds exhibited high inhibitions.

Conclusion::The antiproliferative activity of the synthesized compounds was studied on six selected cancer cell lines. The nature of the heterocyclic ring and the variations of substituted groups showed a high effect through the inhibitions of the tested compound.

Об авторах

Rafat Mohareb

Department of Chemistry, Cairo University

Автор, ответственный за переписку.
Email: info@benthamscience.net

Rehab Ibrahim

Department of Chemistry,, High Institute For Engineering and Technology-Obour

Email: info@benthamscience.net

Fatma Al Farouk

School of Life and Medical Sciences, University of Hertfordshire, Hosted by Global Academic Foundation,

Email: info@benthamscience.net

Ensaf Alwan

Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries,, Future University in Egypt

Email: info@benthamscience.net

Список литературы

  1. Mahmoud, N.F.H.; El-Sewedy, A. Facile synthesis of novel heterocyclic compounds based on pyridine moiety with pharmaceutical activities. J. Heterocycl. Chem., 2020, 57(4), 1559-1572. doi: 10.1002/jhet.3881
  2. Lim, S.J.; Fox, P. Effects of halogenated aromatics/aliphatics and nitrogen(N)-heterocyclic aromatics on estimating the persistence of future pharmaceutical compounds using a modified QSAR model. Sci. Total Environ., 2014, 470-471, 348-355. doi: 10.1016/j.scitotenv.2013.09.089 PMID: 24144939
  3. Srivastava, V.; Singh, P.K.; Tivari, S.; Singh, P.P. Visible light photocatalysis in the synthesis of pharmaceutically relevant heterocyclic scaffolds. Org. Chem. Front., 2022, 9(5), 1485-1507. doi: 10.1039/D1QO01602D
  4. Kabir, E.; Uzzaman, M. A review on biological and medicinal impact of heterocyclic compounds. Results Chem., 2022, 4, 100606. doi: 10.1016/j.rechem.2022.100606
  5. Sallam, E.R.; Aboulnaga, S.F.; Samy, A.M.; Beltagy, D.M.; Desouky, J.M.E.; Abdel-Hamid, H.; Fetouh, H.A. Synthesis, characterization of new heterocyclic compound: Pyrazolyl hydrazino quinoxaline derivative: 3-5-(hydroxy1methyl)-1-phenylpyrazol-3-yl-2-2, 4, 5-trimethoxybenzylidine hydrazonyl-quinoxaline of potent antimicrobial, antioxidant, antiviral, and antitumor activity. J. Mol. Struct., 2023, 1271, 133983. doi: 10.1016/j.molstruc.2022.133983
  6. Banerjee, A.G.; Kothapalli, L.P.; Sharma, P.A.; Thomas, A.B.; Nanda, R.K.; Shrivastava, S.K.; Khatanglekar, V.V. A facile microwave assisted one pot synthesis of novel xanthene derivatives as potential anti-inflammatory and analgesic agents. Arab. J. Chem., 2016, 9, S480-S489. doi: 10.1016/j.arabjc.2011.06.001
  7. Taghartapeh, M.R.; Noroozi Pesyan, N.; Rashidnejad, H.; Khavasi, H.R.; Soltani, A. Synthesis, spectroscopic and photophysical studies of xanthene derivatives. J. Mol. Struct., 2017, 1149, 862-873. doi: 10.1016/j.molstruc.2017.08.054
  8. Kusampally, U.; Pagadala, R.; Kamatala, C.R. Metal free Lewis acid promoted one-pot synthesis of 14-aryl-14H dibenzoa,j xanthenes and their simple biological evolution. Tetrahedron Lett., 2017, 58(33), 3316-3318. doi: 10.1016/j.tetlet.2017.07.037
  9. Srinivas Lavanya Kumar, M.; Singh, J.; Manna, S.K.; Maji, S.; Konwar, R.; Panda, G. Diversity oriented synthesis of chromene-xanthene hybrids as anti-breast cancer agents. Bioorg. Med. Chem. Lett., 2018, 28(4), 778-782. doi: 10.1016/j.bmcl.2017.12.065 PMID: 29352645
  10. Khaki, D.; Namazi, H.; Amininasab, S.M. Synthesis and identification of new thermostable polyamides containing xanthene units with antibacterial properties and relevant composite grafted with modified GO nanoparticles. React. Funct. Polym., 2021, 158, 104780. doi: 10.1016/j.reactfunctpolym.2020.104780
  11. Gong, J.; Liu, C.; Jiao, X.; He, S.; Zhao, L.; Zeng, X. Novel mitochondria-targeted viscosity probe based on a fluorescent rotatable xanthene-hemicyanine dyad. Microchem. J., 2020, 158, 105191. doi: 10.1016/j.microc.2020.105191
  12. Almalki, F.A. An overview of structure-based activity outcomes of pyran derivatives against Alzheimer’s disease. Saudi Pharm. J., 2023, 31(6), 998-1018. doi: 10.1016/j.jsps.2023.04.030 PMID: 37234350
  13. Zhang, C.; Wu, J.; Liu, W.; Zhang, W.; Lee, C.S.; Wang, P. NIR-II xanthene dyes with structure-inherent bacterial targeting for efficient photothermal and broad-spectrum antibacterial therapy. Acta Biomater., 2023, 159, 247-258. doi: 10.1016/j.actbio.2023.01.031 PMID: 36724864
  14. Abdel-Lateef, M.A.; Omar, M.A.; Ali, R.; Derayea, S.M. Xanthene based spectroscopic probe for the analysis of HCV antiviral, daclatasvir dihydrochloride, through feasible complexation reaction. Microchem. J., 2019, 145, 672-675. doi: 10.1016/j.microc.2018.11.038
  15. Gerstmeier, J.; Kretzer, C.; Di Micco, S.; Miek, L.; Butschek, H.; Cantone, V.; Bilancia, R.; Rizza, R.; Troisi, F.; Cardullo, N.; Tringali, C.; Ialenti, A.; Rossi, A.; Bifulco, G.; Werz, O.; Pace, S. Novel benzoxanthene lignans that favorably modulate lipid mediator biosynthesis: A promising pharmacological strategy for anti-inflammatory therapy. Biochem. Pharmacol., 2019, 165, 263-274. doi: 10.1016/j.bcp.2019.03.003 PMID: 30836057
  16. Maia, M.; Resende, D.I.S.P.; Durães, F.; Pinto, M.M.M.; Sousa, E. Xanthenes in medicinal chemistry – synthetic strategies and biological activities. Eur. J. Med. Chem., 2021, 210, 113085. doi: 10.1016/j.ejmech.2020.113085 PMID: 33310284
  17. Rahimi, J.; Maleki, A. Preparation of a trihydrazinotriazine-functionalized core-shell nanocatalyst as an extremely efficient catalyst for the synthesis of benzoxanthenes. Mater. Today Chem., 2020, 18, 100362. doi: 10.1016/j.mtchem.2020.100362
  18. Kefayati, H.; Bazargard, S.J.; Vejdansefat, P.; Shariati, S.; Kohankar, A.M. Fe3O4@MCM-41-SO3H@HMImHSO4: An effective magnetically separable nanocatalyst for the synthesis of novel spirobenzoxanthene-indolinediones. Dyes Pigments, 2016, 125, 309-315. doi: 10.1016/j.dyepig.2015.10.034
  19. Safaei-Ghomi, J.; Eshteghal, F. Nano-Fe3O4/PEG/succinic anhydride: A novel and efficient catalyst for the synthesis of benzoxanthenes under ultrasonic irradiation. Ultrason. Sonochem., 2017, 38, 488-495. doi: 10.1016/j.ultsonch.2017.03.047 PMID: 28633851
  20. Quintás, D.; García, A.; Domínguez, D. Synthesis of spiropyrrolidine or piperidine-3,9′-xanthenes by anionic cycloacylation of carbamates. Tetrahedron Lett., 2003, 44(52), 9291-9294. doi: 10.1016/j.tetlet.2003.10.065
  21. Mroß, G.; Reinke, H.; Fischer, C.; Langer, P. Synthesis of functionalized 2-alkoxybenzoates, 2-aryloxybenzoates and xanthones based on formal 3+3 cyclocondensations of 3-alkoxy- and 3-aryloxy-1-silyloxy-1,3-butadienes with 3-silyloxy-2-en-1-ones. Tetrahedron, 2009, 65(19), 3910-3917. doi: 10.1016/j.tet.2009.02.052
  22. Anna, C.Z.; Chen, Z.; Qiao, H.; Gao, J.; Zhu, M.; Li, C. Synthesis of xanthones from 4-(2-phenoxyphenyl)-1-tosyl-1H-1,2,3-triazole via rhodium-catalyzed annulation/oxidation. Catal. Commun., 2021, 161, 106360. doi: 10.1016/j.catcom.2021.106360
  23. Sahoo, S.R.; Singh, V.K. Brønsted acid catalyzed friedel–crafts alkylation of naphthols with in situ generated naphthol-derived ortho -quinone methides: Synthesis of chiral and achiral xanthene derivatives. J. Org. Chem., 2023, 88(5), 3159-3172. doi: 10.1021/acs.joc.2c02939 PMID: 36866580
  24. Mohareb, R.M.; Mukhtar, S.; Parveen, H.; Abdelaziz, M.A.; Alwan, E.S. Anti-proliferative, morphological and molecular dockingstudies of new thiophene derivatives and their strategy in ionic liquids immobilized reactions. Anticancer. Agents Med. Chem., 2024, 24(9), 4748.
  25. Tandon, R.; Tandon, N.; Patil, S.M. Overview on magnetically recyclable ferrite nanoparticles: Synthesis and their applications in coupling and multicomponent reactions. RSC Advances, 2021, 11(47), 29333-29353. doi: 10.1039/D1RA03874E PMID: 35479579
  26. Mohareb, R.M.; Abdallah, A.E.M.; Abdelaziz, M.A. New approaches for the synthesis of pyrazole, thiophene, thieno2,3-bpyridine, and thiazole derivatives together with their anti-tumor evaluations. Med. Chem. Res., 2014, 23(2), 564-579. doi: 10.1007/s00044-013-0664-7
  27. Mohareb, R.M.; Wardakhan, W.W.; Hamed, F.I. Synthesis and cytotoxicity of fused thiophene and pyrazole derivatives derived from 2-N-acetyl-3-cyano-4,5,6,7-tetrahydrobenzobthiophene. Med. Chem. Res., 2015, 24(5), 2043-2054. doi: 10.1007/s00044-014-1273-9
  28. Mohareb, R.M.; Zaki, M.Y.; Abbas, N.S. Synthesis, anti-inflammatory and anti-ulcer evaluations of thiazole, thiophene, pyridine and pyran derivatives derived from androstenedione. Steroids, 2015, 98, 80-91. doi: 10.1016/j.steroids.2015.03.001 PMID: 25759119
  29. Liu, L.; Siegmund, A.; Xi, N.; Kaplan-Lefko, P.; Rex, K.; Chen, A.; Lin, J.; Moriguchi, J.; Berry, L.; Huang, L.; Teffera, Y.; Yang, Y.; Zhang, Y.; Bellon, S.F.; Lee, M.; Shimanovich, R.; Bak, A.; Dominguez, C.; Norman, M.H.; Harmange, J.C.; Dussault, I.; Kim, T.S. Discovery of a potent, selective, and orally bioavailable c-met inhibitor: 1-(2-hydroxy-2-methylpropyl)- N-(5-(7-methoxyquinolin-4-yloxy)pyridin-2-yl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (AMG 458). J. Med. Chem., 2008, 51(13), 3688-3691. doi: 10.1021/jm800401t PMID: 18553959
  30. Ismail, L.A.; Alfaifi, M.Y.; Elbehairi, S.E.I.; Elshaarawy, R.F.M.; Gad, E.M.; El-Sayed, W.N. Hybrid organoruthenium(II) complexes with thiophene-β-diketo-benzazole ligands: Synthesis, optical properties, CT-DNA interactions and anticancer activity. J. Organomet. Chem., 2021, 949, 121960. doi: 10.1016/j.jorganchem.2021.121960
  31. Romagnoli, R.; Preti, D.; Hamel, E.; Bortolozzi, R.; Viola, G.; Brancale, A.; Ferla, S.; Morciano, G.; Pinton, P. Concise synthesis and biological evaluation of 2-Aryl-3-Anilinobenzobthiophene derivatives as potent apoptosis-inducing agents. Bioorg. Chem., 2021, 112, 104919. doi: 10.1016/j.bioorg.2021.104919 PMID: 33957538
  32. Hollick, J.J.; Golding, B.T.; Hardcastle, I.R.; Martin, N.; Richardson, C.; Rigoreau, L.J.M.; Smith, G.C.M.; Griffin, R.J. 2,6-Disubstituted pyran-4-one and thiopyran-4-one inhibitors of DNA-Dependent protein kinase (DNA-PK). Bioorg. Med. Chem. Lett., 2003, 13(18), 3083-3086. doi: 10.1016/S0960-894X(03)00652-8 PMID: 12941339
  33. Dömling, A. Recent developments in isocyanide based multicomponent reactions in applied chemistry. Chem. Rev., 2006, 106(1), 17-89. doi: 10.1021/cr0505728 PMID: 16402771
  34. Rivera, D.G.; León, F.; Concepción, O.; Morales, F.E.; Wessjohann, L.A. A multiple multicomponent approach to chimeric peptide-peptoid podands. Chemistry, 2013, 19(20), 6417-6428. doi: 10.1002/chem.201201591 PMID: 23512744
  35. Azgomi, A.; Mokhtary, M. Nano-Fe3O4@SiO2 supported ionic liquid as an efficient catalyst for the synthesis of 1,3-thiazolidin-4-ones under solvent-free conditions. J. Mol. Catal. A Chem., 2013, 398, 58-64. doi: 10.1016/j.molcata.2014.11.018
  36. Ugi, I.; Werner, B.; Dömling, A. The chemistry of isocyanides, their multicomponent reactions and their libraries. Molecules, 2003, 8(1), 53-66. doi: 10.3390/80100053
  37. Azgomi, N.; Mokhtary, M. Nano-Fe3O4@SiO2 supported ionic liquid as an efficient catalyst for the synthesis of 1,3-thiazolidin-4-ones under solvent-free conditions. J. Mol. Catal. Chem., 2015, 398, 58-64. doi: 10.1016/j.molcata.2014.11.018
  38. Peach, M.L.; Tan, N.; Choyke, S.J.; Giubellino, A.; Athauda, G.; Burke, T.R., Jr; Nicklaus, M.C.; Bottaro, D.P.; Bottaro, D.P. Directed discovery of agents targeting the Met tyrosine kinase domain by virtual screening. J. Med. Chem., 2009, 52(4), 943-951. doi: 10.1021/jm800791f PMID: 19199650
  39. De Bacco, F.; Luraghi, P.; Medico, E.; Reato, G.; Girolami, F.; Perera, T.; Gabriele, P.; Comoglio, P.M.; Boccaccio, C. Induction of MET by ionizing radiation and its role in radioresistance and invasive growth of cancer. J. Natl. Cancer Inst., 2011, 103(8), 645-661. doi: 10.1093/jnci/djr093 PMID: 21464397
  40. Knudsen, B.S.; Gmyrek, G.A.; Inra, J.; Scherr, D.S.; Vaughan, E.D.; Nanus, D.M.; Kattan, M.W.; Gerald, W.L.; Vande Woude, G.F. High expression of the Met receptor in prostate cancer metastasis to bone. Urology, 2002, 60(6), 1113-1117. doi: 10.1016/S0090-4295(02)01954-4 PMID: 12475693
  41. Humphrey, P.A.; Zhu, X.; Zarnegar, R.; Swanson, P.E.; Ratliff, T.L.; Vollmer, R.T.; Day, M.L. Hepatocyte growth factor and its receptor (c-MET) in prostatic carcinoma. Am. J. Pathol., 1995, 147(2), 386-396. PMID: 7639332
  42. Rubin, J.; Bottaro, D.P.; Aaronson, S.A. Hepatocyte growth factor/scatter factor and its receptor, the c-met proto-oncogene product. Biochim. Biophys. Acta Rev. Cancer, 1993, 1155(3), 357-371. doi: 10.1016/0304-419X(93)90015-5 PMID: 8268192
  43. Organ, S.L.; Tsao, M.S. An overview of the c-MET signaling pathway. Ther. Adv. Med. Oncol., 2011, 3(1_suppl(Suppl.)), S7-S19. doi: 10.1177/1758834011422556 PMID: 22128289
  44. Jeffers, M.; Rong, S.; Vande Woude, G.F. Hepatocyte growth factor/scatter factor—Met signaling in tumorigenicity and invasion/metastasis. J. Mol. Med. (Berl.), 1996, 74(9), 505-513. doi: 10.1007/BF00204976 PMID: 8892055
  45. Verras, M.; Lee, J.; Xue, H.; Li, T.H.; Wang, Y.; Sun, Z. The androgen receptor negatively regulates the expression of c-Met: Implications for a novel mechanism of prostate cancer progression. Cancer Res., 2007, 67(3), 967-975. doi: 10.1158/0008-5472.CAN-06-3552 PMID: 17283128
  46. Li, S.; Zhao, Y.; Wang, K.; Gao, Y.; Han, J.; Cui, B.; Gong, P. Discovery of novel 4-(2-fluorophenoxy)quinoline derivatives bearing 4-oxo-1,4-dihydrocinnoline-3-carboxamide moiety as c-Met kinase inhibitors. Bioorg. Med. Chem., 2013, 21(11), 2843-2855. doi: 10.1016/j.bmc.2013.04.013 PMID: 23628470
  47. Gieni, R.S.; Li, Y. HayGlass, K.T. Comparison of 3Hthymidine incorporation with MTT- and MTS-based bioassays for human and murine IL-2 and IL-4 analysis Tetrazolium assays provide markedly enhanced sensitivity. J. Immunol. Methods, 1995, 187(1), 85-93. doi: 10.1016/0022-1759(95)00170-F PMID: 7490461
  48. Devoos, L.; Biguenet, A.; Rousselot, J.; Bour, M.; Plésiat, P.; Fournie, D.; Jeannot, K. Performance of discs, sensititre EUMDROXF microplates and MTS gradient strips for the determination of the susceptibility of multidrug-resistant Pseudomonas aeruginosa to cefiderocol. Clin. Microbiol. Infect., 2023, 29(5), 652.e1-652.e8. doi: 10.1016/j.cmi.2022.12.021
  49. Zhao, R.; Cai, K.; Yang, J.J.; Zhou, Q.; Cao, W.; Xiang, J.; Shen, Y.H.; Cheng, L.L.; Zang, W.D.; Lin, Y.; Yuan, Y.Y.; Xu, W.; Tao, H.; Zhao, S.M.; Zhao, J.Y. Nuclear ATR lysine-tyrosylation protects against heart failure by activating DNA damage response. Cell Rep., 2023, 42(4), 112400. doi: 10.1016/j.celrep.2023.112400 PMID: 37071536
  50. Liu, L.; Simon, M.; Muggiolu, G.; Vilotte, F.; Antoine, M.; Caron, J.; Kantor, G.; Barberet, P.; Seznec, H.; Audoin, B. Changes in intra-nuclear mechanics in response to DNA damaging agents revealed by time-domain Brillouin micro-spectroscopy. Photoacoustics, 2022, 27, 100385. doi: 10.1016/j.pacs.2022.100385 PMID: 36068801
  51. Nunhart, P.; Konkoľová, E.; Janovec, L.; Jendželovský, R.; Vargová, J.; Ševc, J.; Matejová, M.; Miltáková, B.; Fedoročko, P.; Kozurkova, M. Fluorinated 3,6,9-trisubstituted acridine derivatives as DNA interacting agents and topoisomerase inhibitors with A549 antiproliferative activity. Bioorg. Chem., 2020, 94, 103393. doi: 10.1016/j.bioorg.2019.103393 PMID: 31679839

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