Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents)
  4. Fast Track Articles
  5. Fast Track Article
image of Uses of Cyclohexan-1,3-diones to Synthesis Xanthenes Derivatives with Anti-proliferative Activity Against Cancer Cell Lines and their Inhibitions Toward Tyrosine Kinases

Abstract

Background

Xanthene derivatives are a notable class of heterocyclic compounds widely studied for their significant biological impact. These molecules, found in both natural and synthetic forms, have attracted substantial scientific interest due to their broad spectrum of biological activities. The xanthene nucleus, in particular, is associated with a range of potential pharmaceutical properties, including antibacterial, antiviral, anti-inflammatory, anticancer, and antioxidant effects. Their structural flexibility allows for modifications that can enhance specific biological functions, making them valuable candidates in medicinal chemistry and drug development.

Objective

Multi-component reactions involving two equivalents of 5,5-dimethylcyclohexane-1,3-dione with aromatic aldehydes yield xanthene derivatives that are known for their biological activity. Additionally, fused xanthene derivatives are formed through subsequent heterocyclization reactions, resulting in compounds with a broad range of biological properties.

Methods

Various xanthene derivatives incorporating thiophene and thiazole moieties were synthesized. Compounds were further subjected to heterocyclization reactions to produce fused xanthene derivatives with additional heterocyclic components, enhancing their biological activity. The cytotoxic effects of the synthesized compounds were assessed across six cancer cell lines. Inhibition studies on c-Met kinase and the PC-3 cell line were conducted.

Result

Additionally, the compounds' inhibitory activity against tyrosine kinases was evaluated, and morphological changes in the A549 cell line were observed with the two most potent compounds.

Conclusion

The synthesized heterocyclic compounds, derived from 5,5-dimethylcyclohexane-1,3-dione and related cyclohexanone derivatives, exhibited significant inhibitory effects across various cancer cell lines. Specifically, compounds , , , , , , , , , , , , , , , , , , and demonstrated high levels of inhibition, indicating potential for further exploration of xanthene-based heterocyclic compounds to enhance anticancer properties.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/acamc/10.2174/0118715206350037241206062610
2025-01-16
2025-03-29

  • From This Site

    /content/journals/acamc/10.2174/0118715206350037241206062610
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Rajan D. Rajamanikandan R. Ilanchelian M. Exploring the photophysical interaction of xanthene dyes with gold nanorods by optical spectroscopic techniques and in-vitro cytotoxicity studies of dye-nano conjugates. Dyes Pigments 2023 220 111746 10.1016/j.dyepig.2023.111746
    [Google Scholar]
  2. Khan Z. Sekar N. Effect of spirocyclization of xanthene dyes on linear and nonlinear optical properties by considering D-π-A and D-A-D Systems: DFT and TD-DFT approach. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2024 314 124183 10.1016/j.saa.2024.124183 38554693
    [Google Scholar]
  3. Sharma S. Mohan D. Singh N. Sharma M. Sharma A.K. Spectroscopic and lasing properties of Xanthene dyes encapsulated in silica and polymeric matrices. Optik (Stuttg.) 2010 121 1 11 18 10.1016/j.ijleo.2008.05.005
    [Google Scholar]
  4. Kalampaliki A.D. Vincent S. Mallick S. Le H.N. Barnoin G. More Y.W. Burger A. Dotsikas Y. Gikas E. Michel B.Y. Kostakis I.K. Synthesis, spectroscopic and computational evaluation of a xanthene-based fluorogenic derivatization reagent for the determination of primary amines. Dyes Pigments 2021 196 109798 10.1016/j.dyepig.2021.109798
    [Google Scholar]
  5. Wu Y. Lun W. Zeng H. Guo X. Yang M. Lan Q. A facile near-infrared xanthene fluorescence probe for visualizing of hypochlorous acid in vitro and in vivo. Anal. Chim. Acta 2024 1294 342292 10.1016/j.aca.2024.342292 38336413
    [Google Scholar]
  6. El Mesky M. Zgueni H. Rhazi Y. El-Guourrami O. Abchir O. Jabha M. Nakkabi A. Chtita S. Achamlale S. Chalkha M. Chebabe D. Mabrouk E.H. Prediction by DFT and synthesis of new xanthene derivatives: Evaluation of their toxicity and antihyperlipidemic properties in vivo and in silico. J. Mol. Struct. 2024 1313 138705 10.1016/j.molstruc.2024.138705
    [Google Scholar]
  7. Mennana I. Nemouchi S. Sehout I. Krid A. Boulcina R. Mechouche M.S. Debache A. Synthesis, characterization, in silico molecular docking and antibacterial properties of some tetrahydrobenzo[a]xanthene-11-ones. Org. Prep. Proced. Int. 2024 56 4 379 391 10.1080/00304948.2024.2327227
    [Google Scholar]
  8. Ranjbari S. Jarrahpour A. Heiran R. Sepehri S. Kianpour S. Ghasemi Y. Dibenzoxanthene-β-lactam hybrids as potential antioxidant and anticancer agents: Synthesis, biological evaluation, and docking study. J. Mol. Struct. 2025 1322 140455 10.1016/j.molstruc.2024.140455
    [Google Scholar]
  9. 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 10.1016/j.reactfunctpolym.2020.104780
    [Google Scholar]
  10. Kaur N. Dhairwal P. Brar A. Kaur G. Bhalla A. Prakash C. Chaudhary G.R. Amphiphilic metallosurfactants as potential scaffolds for facile fabrication of PdO-NiO nanocomposites for environmentally benign synthesis of xanthene derivatives. Mater. Today Chem. 2019 14 100194 10.1016/j.mtchem.2019.100194
    [Google Scholar]
  11. Bongard R.D. Lepley M. Gastonguay A. Syrlybaeva R.R. Talipov M.R. Jones Lipinski R.A. Leigh N.R. Brahmbhatt J. Kutty R. Rathore R. Ramchandran R. Sem D.S. Discovery and characterization of halogenated xanthene inhibitors of DUSP5 as potential photodynamic therapeutics. J. Photochem. Photobiol. Chem. 2019 375 114 131 10.1016/j.jphotochem.2019.01.005 31839699
    [Google Scholar]
  12. Niasar F.N. Moradian M. Synthesis of some derivatives of 1,8-dioxo-octa-hydro xanthene and 9-aryl-hexahydro acridine-1,8-dione using metal ion-exchanged NaY zeolite as heterogeneous catalyst. RSC Advances 2024 14 15 10322 10330 10.1039/D3RA03020B 38549799
    [Google Scholar]
  13. Parhad A.R. Aute D.S. Gadhave A.G. Uphade B.K. Synthesis of tetrahydrobenzo[a]xanthene-11-ones by indium sulfide nanoparticles as green an efficient and reusable catalyst under solvent-free condition. J. Sulfur Chem. 2024 45 4 459 476 10.1080/17415993.2024.2350389
    [Google Scholar]
  14. Karimian A. Norouzi M. Ebrahimnia A. Nozari A. Fe3O4@SiO2@APTES@MPIB-Mn(II) as an eco-friendly and magnetically recyclable nano catalyst for the green synthesis of various xanthene derivatives. J. Mol. Struct. 2024 1297 137014 10.1016/j.molstruc.2023.137014
    [Google Scholar]
  15. Alotaibi M.A. Alharthi A.I. Qahtan T.F. Alotibi S. Ali I. Bakht M.A. Green synthesis of xanthene derivatives through visible light-driven photocatalysis using blackberry dye-sensitized TiO2. J. Alloys Compd. 2024 978 173388 10.1016/j.jallcom.2023.173388
    [Google Scholar]
  16. Nasseri S. Kiasat A.R. Designing of a novel dual-function cross-linked wrinkled fibrous silica nanocomposite containing bipyridinum dichloride bridges and brønsted acidic unites and its catalytic application in xanthene synthesis. J. Taiwan Inst. Chem. Eng. 2024 157 105402 10.1016/j.jtice.2024.105402
    [Google Scholar]
  17. Luo Y. Shi M. Dong L. Xie T. Lartey P.O. Zhao S. Guo K. Wang H. Miao Y. Li J. Synthesis and properties of naphthylamine derivative functionalized spiro-[fluorene-9,9′-xanthene] for single-component white light-emitting diodes. J. Mol. Struct. 2024 1317 139122 10.1016/j.molstruc.2024.139122
    [Google Scholar]
  18. Merroun Y. Chehab S. El Hallaoui A. Guedira T. Boukhris S. Ghailane R. Souizi A. Synthesis, characterization, and catalytic application of SnP 2 O 7 for the highly efficient synthesis of xanthene derivatives. Polycycl. Aromat. Compd. 2024 44 7 4349 4363 10.1080/10406638.2023.2247128
    [Google Scholar]
  19. Naderi S. Sandaroos R. Peiman S. Maleki B. Novel crowned cobalt (II) complex containing an ionic liquid: A green and efficient catalyst for the one-pot synthesis of chromene and xanthene derivatives starting from benzylic alcohols. J. Phys. Chem. Solids 2023 180 111459 10.1016/j.jpcs.2023.111459
    [Google Scholar]
  20. Londhe G.S. Gnanaprakasam B. FeCl 3 ⋅ 6H 2 O mediated sequential oxidative cleavage and spiro coupling of peroxyoxindole with cyclic‐1,3‐diketone/1‐naphthol for the synthesis of spirooxindolo‐xanthene derivatives. Asian J. Org. Chem. 2023 12 11 e202300358 10.1002/ajoc.202300358
    [Google Scholar]
  21. Thanaraj C. Alagesan M. Velladurai R. Reusable SiO 2 @NiO core-shell nanoparticles catalyzed efficient synthesis of 14-aryl-14 H -dibenzo [a,i] xanthene-8, 13-dione derivatives. Synth. Commun. 2023 53 23 2002 2017 10.1080/00397911.2023.2261571
    [Google Scholar]
  22. Taib L.A. Keshavarz M. Panahimehr M. Introduction of click synthesized novel organic-inorganic solid acid catalysts for highly promoted synthesis of substituted xanthenes. Polycycl. Aromat. Compd. 2023 43 3 2233 2249 10.1080/10406638.2022.2128380
    [Google Scholar]
  23. Mohamadpour F. Supramolecular β -cyclodextrin as a reusable catalyst for xanthene synthesis in aqueous medium. Org. Prep. Proced. Int. 2023 55 4 317 325 10.1080/00304948.2022.2141047
    [Google Scholar]
  24. Alsharif M.A. Ahmed N. Issa Alahmdi M. Mukhtar S. Parveen H. Obaid R.J. Almalki A.S.A. Divergent synthesis of fused Benzo-xanthene and oxazine derivatives via Cu-catalyst. J. Saudi Chem. Soc. 2022 26 6 101568 10.1016/j.jscs.2022.101568
    [Google Scholar]
  25. Chawala V. Kheto A. Sharma L. Sehrawat R. Chapter Two - Microwave and ultrasound-assisted sample preparation as green analytical technology in food analysis. Green Chemistry in Food Analysis Conventional and Emerging Approaches 2024 25 43
    [Google Scholar]
  26. Kajal K. Shakya R. Rashid M. Nigam V. Kurmi B.D. Gupta G.D. Patel P. Recent green chemistry approaches for pyrimidine derivatives as a potential anti-cancer agent: An overview (2013–2023). Sustain. Chem. Pharm. 2024 37 101374 10.1016/j.scp.2023.101374
    [Google Scholar]
  27. Verma C. Chauhan D.S. Aslam R. Banerjee P. Aslam J. Quadri T.W. Zehra S. Verma D.K. Quraishi M.A. Dubey S. AlFantazi A. Rasheed T. Principles and theories of green chemistry for corrosion science and engineering: design and application. Green Chem. 2024 26 8 4270 4357 10.1039/D3GC05207A
    [Google Scholar]
  28. Majhi S. Applications of ultrasound in total synthesis of bioactive natural products: A promising green tool. Ultrason. Sonochem. 2021 77 105665 10.1016/j.ultsonch.2021.105665 34298310
    [Google Scholar]
  29. Fujita M. Furusho Y. Ultrasound-assisted synthesis of substituted guanidines using 1H-pyrazole-1-carboxamidine and S-methylisothiouronium sulfate under solvent-free conditions. Tetrahedron 2018 74 32 4339 4342 10.1016/j.tet.2018.06.057
    [Google Scholar]
  30. Bhosale M.A. Ummineni D. Sasaki T. Nishio-Hamane D. Bhanage B.M. Magnetically separable γ-Fe2O3 nanoparticles: An efficient catalyst for acylation of alcohols, phenols, and amines using sonication energy under solvent free condition. J. Mol. Catal. Chem. 2015 404-405 8 17 10.1016/j.molcata.2015.04.002
    [Google Scholar]
  31. Sahu C.C. Biswas S. Hommelsheim R. Bolm C. Synthesis of α-ketothioamides with elemental sulfur under solvent-free conditions in a mixer mill. RSC Mechanochemistry 2024 1 1 38 42 10.1039/D3MR00025G
    [Google Scholar]
  32. Tasic G. Mitrovic N. Simic M. Koravovic M. Jovanovic P. Petkovic M. Jovanovic M. Ivkovic B. Savic V. Synthesis of hydantoins from N‐Boc protected amino acid derived amides using polymer‐supported PPh 3 / CBr 4 as a reagent. J. Heterocycl. Chem. 2024 61 5 753 760 10.1002/jhet.4802
    [Google Scholar]
  33. Ma B. Yao J. Knudsen T.Š. Chen Z. Liu B. Zhao C. Zhu X. Simultaneous removal of typical flotation reagent 8-hydroxyquinoline and Cr(VI) through heterogeneous Fenton-like processes mediated by polydopamine functionalized ATP supported nZVI. J. Hazard. Mater. 2022 424 Pt C 126698 10.1016/j.jhazmat.2021.126698 34315632
    [Google Scholar]
  34. Mohareb R.M. Ibrahim R.A. Al Farouk F.O. Alwan E.S. Ionic liquid immobilized synthesis of new xantheses derivatives and their antiproliferative, molecular docking and morphological studies. Anticancer. Agents Med. Chem. 2024 24 13 990 1008 10.2174/0118715206299407240324110505 38685778
    [Google Scholar]
  35. Mohareb R.M. Mukhtar S. Parveen H. Abdelaziz M.A. Alwan E.S. Anti-proliferative, morphological and molecular docking studies of new thiophene derivatives and their strategy in ionic liquids immobilized reactions. Anticancer. Agents Med. Chem. 2024 24 9 691 708 10.2174/0118715206262307231122104748 38321904
    [Google Scholar]
  36. Reeve A.M. Reaction of dimedone and benzaldehyde: A discovery-based lab for second-semester organic chemistry. J. Chem. Educ. 2015 92 3 582 585 10.1021/ed400457c
    [Google Scholar]
  37. Wang D.L. Wu J.Y. Cui Q.T. An efficient one-pot synthesis of thiophene-fused pyrido[3,2-a]azulenes via Gewald reaction. Chin. Chem. Lett. 2014 25 12 1591 1594 10.1016/j.cclet.2014.07.007
    [Google Scholar]
  38. El-Borai M.A. Rizk H.F. Ibrahim S.A. Fares A.K. An eco‐friendly synthesis and biological screening of fused heterocyclic compounds containing a thiophene moiety via Gewald reaction. J. Heterocycl. Chem. 2019 56 10 2787 2795 10.1002/jhet.3658
    [Google Scholar]
  39. Barnes D.M. Haight A.R. Hameury T. McLaughlin M.A. Mei J. Tedrow J.S. Riva Toma J.D. New conditions for the synthesis of thiophenes via the Knoevenagel/Gewald reaction sequence. Application to the synthesis of a multitargeted kinase inhibitor. Tetrahedron 2006 62 49 11311 11319 10.1016/j.tet.2006.07.008
    [Google Scholar]
  40. Savickienė V. Bieliauskas A. Belyakov S. Šačkus A. Arbačiauskienė E. Synthesis and characterization of novel biheterocyclic compounds from 3‐alkoxy‐1 H ‐pyrazole‐4‐carbaldehydes via multicomponent reactions. J. Heterocycl. Chem. 2024 61 6 927 947 10.1002/jhet.4804
    [Google Scholar]
  41. Zhong Y. Arylformylacetonitriles in multicomponent reactions leading to heterocycles. Eur. J. Org. Chem. 2022 2022 48 e202201038 10.1002/ejoc.202201038
    [Google Scholar]
  42. Mandal A. Khan A.T. Recent advancement in the synthesis of quinoline derivatives via multicomponent reactions. Org. Biomol. Chem. 2024 22 12 2339 2358 10.1039/D4OB00034J 38444342
    [Google Scholar]
  43. Jelizi H. Toumi A. Abdella F.I.A. Daoud I. Boudriga S. Alshamari A.K. Alanazi T.Y.A. Alrashdi A.A. Edziri H. Knorr M. Kirchhoff J.L. Strohmann C. Asymmetric synthesis of enantiopure tetracyclic dispirooxindolopyrrolidine-piperidones via microwave-assisted multicomponent reaction: Crystallographic analysis, antimicrobial activity and in silico studies. J. Mol. Struct. 2024 1308 138104 10.1016/j.molstruc.2024.138104
    [Google Scholar]
  44. 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 10.1021/jm800791f 19199650
    [Google Scholar]
  45. 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 10.1093/jnci/djr093 21464397
    [Google Scholar]
  46. Jabbarzadeh Kaboli P. Chen H.F. Babaeizad A. Roustai Geraylow K. Yamaguchi H. Hung M.C. Unlocking c-MET: A comprehensive journey into targeted therapies for breast cancer. Cancer Lett. 2024 588 216780 10.1016/j.canlet.2024.216780 38462033
    [Google Scholar]
  47. Raju R.M. Joy J.A. Manjunathaiah R.N. Justin A. Kumar B.R. EGFR as therapeutic target to develop new generation tyrosine kinase inhibitors against breast cancer: A critical. Results Chem. 2024 7 101490
    [Google Scholar]
  48. Organ S.L. Tsao M.S. An overview of the c-MET signaling pathway. Ther. Adv. Med. Oncol. 2011 3 1_suppl S7 S19 10.1177/1758834011422556 22128289
    [Google Scholar]
  49. 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 10.1007/BF00204976 8892055
    [Google Scholar]
  50. 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 10.1016/S0090‑4295(02)01954‑4 12475693
    [Google Scholar]
  51. 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 7639332
    [Google Scholar]
  52. 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 10.1158/0008‑5472.CAN‑06‑3552 17283128
    [Google Scholar]
  53. Daoui O. Elkhattabi S. Chtita S. Elkhalabi R. Zgou H. Benjelloun A.T. QSAR, molecular docking and ADMET properties in silico studies of novel 4,5,6,7-tetrahydrobenzo[D]-thiazol-2-Yl derivatives derived from dimedone as potent anti-tumor agents through inhibition of C-Met receptor tyrosine kinase. Heliyon 2021 7 7 e07463 10.1016/j.heliyon.2021.e07463
    [Google Scholar]
  54. 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 10.1016/j.bmc.2013.04.013 23628470
    [Google Scholar]
  55. Zhang C. Sheng M. lv J. Cao Y. Chen D. Jia L. Sun Y. Ren Y. Li L. Weng Y. Yu W. Single-cell analysis reveals the immune heterogeneity and interactions in lungs undergoing hepatic ischemia–reperfusion. Int. Immunopharmacol. 2023 124 Pt B 111043 10.1016/j.intimp.2023.111043 37844464
    [Google Scholar]
/content/journals/acamc/10.2174/0118715206350037241206062610
Loading
Uses of Cyclohexan-1,3-diones to Synthesis Xanthenes Derivatives with Anti-proliferative Activity Against Cancer Cell Lines and their Inhibitions Toward Tyrosine Kinases
Bentham Science Publishers ; https://doi.org/10.2174/0118715206350037241206062610
/content/journals/acamc/10.2174/0118715206350037241206062610
/content/journals/acamc/10.2174/0118715206350037241206062610
Loading

Data & Media loading...


  • Article Type:     Research Article
Keywords: thiazole ; thiophene ; antiproliferative activity ; Xanthene ; tyrosine kinase

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test