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  3. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents)
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Volume 25, Issue 2
  • ISSN: 1871-5206
  • E-ISSN: 1875-5992

Abstract

Background

The coumarin nuclei, which exist in many heterocyclic compounds, has gained a lot of attention over the past decade due to their wide range of biological activities such as antibacterial, anticoagulant, antiviral, antifungal, anticancer, and anti-inflammatory properties.

Objective

The multi-component reactions of 5,5-dimethylcyclohexane-1,3-dione with acetophenone derivatives and triethoxymethane produced biologically active target chromene molecules and their fused derivatives.

Methods

The reaction of 5,5-dimethylcyclohexane-1,3-dione and each of triethoxymethane and acetophenone derivatives in absolute ethanol containing triethylamine gave the 4,6,7,8-tetrahydro-5-chromen-5-one derivatives . Compounds were used for further heterocyclization reactions to produce biologically active fused pyrazole, thiophene, and thiazole derivative corporate with the chromenes caffold.

Results

The cytotoxicity of the synthesized compounds were evaluated using six cancer cell lines together with c-Met kinase and PC-3 cell line inhibitions. In addition, cytotoxicity toward hepatocellular carcinoma HepG2 and cervical carcinoma HeLa was carried out as well as the cytotoxic potential for all compounds against peripheral blood lymphocytes (PBL) extracted from healthy donors. Morphological changes of the A549 cell line by the two most active compounds were also studied.

Conclusion

The synthesized heterocyclic compounds were originally obtained from 5,5-dimethylcyclohexane-1,3-dione. Several of the produced compounds exhibited high inhibitions toward several cancer cell lines proving high inhibitions, therefore, encouraging further studies to synthesize heterocyclic compounds based on chromene scaffold.

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2024-09-19
2024-12-26

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References

  1. NoureenS. AliS. IqbalJ. ZiaM.A. HussainT. Synthesis, comparative theoretical and experimental characterization of some new 1,3,5 triazine based heterocyclic compounds and in vitro evaluation as promising biologically active agents.J. Mol. Struct.2022126813362210.1016/j.molstruc.2022.133622
     [Google Scholar]
  2. FetouhH.A. IsmailA.M. HamidH.A. BashierM.O. Synthesis of promising nanocomposites from an antitumer and biologically active heterocyclic compound uploaded by clay and chitosan polymers.Int. J. Biol. Macromol.20191371211122010.1016/j.ijbiomac.2019.06.18731254576
     [Google Scholar]
  3. NguyenH.D. KimM.S. Identification of promising inhibitory heterocyclic compounds against acetylcholinesterase using QSAR, ADMET, biological activity, and molecular docking.Comput. Biol. Chem.202310410787210.1016/j.compbiolchem.2023.10787237119698
     [Google Scholar]
  4. SallamE.R. AboulnagaS.F. SamyA.M. BeltagyD.M. El DesoukyJ.M. Abdel-HamidH. FetouhH.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.2023127113398310.1016/j.molstruc.2022.133983
     [Google Scholar]
  5. NegiM. ChawlaP.A. FarukA. ChawlaV. Role of heterocyclic compounds in SARS and SARS CoV-2 pandemic.Bioorg. Chem.202010410431510.1016/j.bioorg.2020.10431533007742
     [Google Scholar]
  6. RazaM.A. FarwaU. IshaqueF. Al-SehemiA.G. Designing of thiazolidinones against chicken pox, monkey pox, and hepatitis viruses: A computational approach.Comput. Biol. Chem.202310310782710.1016/j.compbiolchem36805155
     [Google Scholar]
  7. DengX. LuoT. ZhangX. LiY. XieL. JiangW. LiuL. WangZ. Design, synthesis and biological evaluation of 3-arylisoquinoline derivatives as topoisomerase I and II dual inhibitors for the therapy of liver cancer.Eur. J. Med. Chem.202223711437610.1016/j.ejmech.2022.11437635462164
     [Google Scholar]
  8. MahurkarN.D. GawhaleN. LokhandeM.N. UkeS.J. KodapeM.M. Benzimidazole: A versatile scaffold for drug discovery and beyond – A comprehensive review of synthetic approaches and recent advancements in medicinal chemistry.Results Chem.2023610113910.1016/j.rechem.2023.101139
     [Google Scholar]
  9. TaleleT.T. AroraP. KulkarniS.S. PatelM.R. SinghS. ChudayeuM. Kaushik-BasuN. Structure-based virtual screening, synthesis and SAR of novel inhibitors of hepatitis C virus NS5B polymerase.Bioorg. Med. Chem.201018134630463810.1016/j.bmc.2010.05.03020627595
     [Google Scholar]
  10. SmithH.M. Sir William Henry Perkin.Torchbearers Chem.19491961838190710.1016/B978‑1‑4831‑9805‑7.50192‑4
     [Google Scholar]
  11. MariappanP. KiranK.R. SwathyP.S. KaniyasseryA. ThoratS.A. BhagyashreeP. ThiruvengadamM. MuthusamyA. Sacred groves and nakshatravan trees - A comparative analysis for their medicinal properties and volatile compounds for human health.S. Afr. J. Bot.202215162363810.1016/j.sajb.2022.08.029
     [Google Scholar]
  12. SantosJr C.M. SilvaS.M.C. SalesE.M. VelozoE.D.S. Dos SantosE.K.P. CanutoG.A.B. AzeredoF.J. BarrosT.F. BiegelmeyerR. Coumarins from Rutaceae: Chemical diversity and biological activities.Fitoterapia202316810548910.1016/j.fitote.2023.10548936990289
     [Google Scholar]
  13. VuaiS.A.H. KhalfanM.S. BabuN.S. DFT and TD-DFT studies for optoelectronic properties of coumarin based donor-π-acceptor (D-π-A) dyes: Applications in dye-sensitized solar cells (DSSCS).Heliyon2021711e0833910.1016/j.heliyon.2021.e0833934816038
     [Google Scholar]
  14. MavazzanA. KambleR.R. MendheA. SankapalB.R. BayannavarP.K. MadarS.F. MetreT.V. PashaK.M.M. KodasiB. NadoniV.B. Synthesis of phenothiazine dyes featuring coumarin unit and CdS NWs as photoanodes for efficient dye-sensitized solar cells.Physica B202366841525310.1016/j.physb.2023.415253
     [Google Scholar]
  15. MandalS. KandregulaG.R. A computational finding on the effect of π-conjugated acceptors in thiophene-linked coumarin dyes for potential suitability in DSSC application.J. Photochem. Photobiol. Chem.2023435, 1232, 11430010.1016/j.jphotochem.2022.114300
     [Google Scholar]
  16. RamasamyA.K. RajamanickamG. BangaruS. PerumalsamyR. The significance of methoxy substitution and π-spacer arrangements on carbazole donor and furofuran π-spacer based promising sensitizers for dye sensitized solar cells.Comput. Theor. Chem.202411446810.1016/j.comptc.2024.114468
     [Google Scholar]
  17. YahyaM. BouzianiA. OcakC. SeferoğluZ. SillanpääM. Organic/metal-organic photosensitizers for dye-sensitized solar cells (DSSC): Recent developments, new trends, and future perceptions.Dyes Pigments202119210922710.1016/j.dyepig.2021.109227
     [Google Scholar]
  18. SouilahM. HachiM. FitriA. BenjellounA.T. BenzakourM. McharfiM. ZgouH. Efficient tuning of various coumarin based donor dyes with diketopyrrolopyrrole by forming D-A′-π-A structure for high-efficiency solar cells: A DFT/TD-DFT study.Chem. Data Collect.20234510101710.1016/j.cdc.2023.101017
     [Google Scholar]
  19. TorresE. SequeiraS. ParreiraP. MendesP. SilvaT. LobatoK. BritesM.J. Coumarin dye with ethynyl group as π-spacer unit for dye sensitized solar cells.J. Photochem. Photobiol. Chem.20153101810.1016/j.jphotochem.2015.05.017
     [Google Scholar]
  20. MartinsS. AvóJ. LimaJ. NogueiraJ. AndradeL. MendesA. PereiraA. BrancoP.S. Styryl and phenylethynyl based coumarin chromophores for dye sensitized solar cells.J. Photochem. Phtobiol. A: Chemistry201835356456910.1016/j.jphotochem.2017.12.018
     [Google Scholar]
  21. MaikhuriV.K. VermaV. MathurD. PrasadA.K. KhatriV. Synthesis of substituted 2H-Chromenes via Pd-catalyzed C-H activation and thermal cyclization.Carbohydr. Res.202453610901810.1016/j.carres.2023.10901838185030
     [Google Scholar]
  22. DashA.K. MukherjeeD. DhulapA. HaiderS. KumarD. Green chemistry appended synthesis, metabolic stability and pharmacokinetic assessment of medicinally important chromene dihydropyrimidinones.Bioorg. Med. Chem. Lett.2019292412675010.1016/j.bmcl.2019.12675031699608
     [Google Scholar]
  23. OstadzadehH. KiyaniH. Multicomponent synthesis of tetrahydrobenzo[b]pyrans, pyrano[2,3-d]pyrimidines, and dihydropyrano[3,2-c]chromenes catalyzed by sodium benzoate.Polycycl. Aromat. Compd.2023Available online.10.1080/10406638.2022.2162091
     [Google Scholar]
  24. ElinsonM.N. VereshchaginA.N. RyzhkovaY.E. KarpenkoK.A. RyzhkovF.V. EgorovM.P. Electrocatalytic cascade selective approach to 3-aryl-2‘H,3H,4H-spiro{Furo[2,3-c]chromene-2,5’-pyrimidine}-2′,4,4′,6‘(1’H,3'H)tetraones and its automatic screening docking studies.Polycycl. Aromat. Compd.20228356837010.1080/10406638.2022.2149568
     [Google Scholar]
  25. LiY. LuoZ. ZhouA. LiuW. FanJ. MiaoJ. GuoB. TangL. FanL. Design and synthesis of novel benzoxazole/chromene-phthalide scaffolds hybrids as potential natural products-based fungicide.Nat. Prod. Res.202438142441244610.1080/14786419.2023.217799336762769
     [Google Scholar]
  26. HuangJ.H. LvJ.M. XieY.F. ZhaoH. XiaoL.Y. DaiP. QinS.Y. HuD. GaoH. YaoX.S. Isolation of new compounds related to xyloketals biosynthesis implies an alternative pathway for furan-fused-chromene formation.Org. Biomol. Chem.202321204309431837171256
     [Google Scholar]
  27. MoharebR.M. MostafaB.M. Uses of ethyl benzoylacetate for the synthesis of thiophene, thiazole, pyridine, and pyran derivatives with antitumor activities.J. Heterocycl. Chem.2020571275129010.1002/jhet.3865
     [Google Scholar]
  28. Abdel-GalilE. MoawadE.B. El-MekabatyA. SaidG.E. Synthesis, characterization and antibacterial activity of some new thiazole and thiazolidinone derivatives containing phenyl benzoate moiety.Synth. Commun.2018482083209210.1080/00397911.2018.1482349
     [Google Scholar]
  29. MoharebR.M. Al-OmranF. AzzamR.A. Heterocyclic ring extension of estrone: synthesis and cytotoxicity of fused pyran, pyrimidine and thiazole derivatives.Steroids201484465610.1016/j.steroids.2014.03.01224686206
     [Google Scholar]
  30. MoharebR.M. ZakiM.Y. AbbasN.S. Synthesis, anti-inflammatory and anti-ulcer evaluations of thiazole, thiophene, pyridine and pyran derivatives derived from androstenedione.Steroids201598809110.1016/j.steroids.2015.03.00125759119
     [Google Scholar]
  31. PeachM.L. TanN. ChoykeS.J. GiubellinoA. AthaudaG. BurkeT.R.Jr NicklausM.C. BottaroD.P. BottaroD.P. Directed discovery of agents targeting the Met tyrosine kinase domain by virtual screening.J. Med. Chem.200952494395110.1021/jm800791f19199650
     [Google Scholar]
  32. BaccoF.D. LuraghiP. MedicoE. ReatoG. GirolamiF. PereraT. GabrieleP. ComoglioP.M. BoccaccioC. J. Natl. Cancer Inst.201110364566121464397
     [Google Scholar]
  33. RubinJ.S. BottaroD.P. AaronsonS.A. Hepatocyte growth factor/scatter factor and its receptor, the c-met proto-oncogene product.Biochim. Biophys. Acta19931155335737110.1016/0304‑419x(93)90015‑58268192
     [Google Scholar]
  34. OrganS.L. TsaoM.S. An overview of the c-MET signaling pathway.Ther. Adv. Med. Oncol.201131Suppl.S7S1910.1177/175883401142255622128289
     [Google Scholar]
  35. JeffersM. RongS. Vande WoudeG.F. Hepatocyte growth factor/scatter factor-Met signaling in tumorigenicity and invasion/metastasis.J. Mol. Med. (Berl.)199674950551310.1007/BF002049768892055
     [Google Scholar]
  36. KnudsenB.S. GmyrekG.A. InraJ. ScherrD.S. VaughanE.D. NanusD.M. KattanM.W. GeraldW.L. VandeW.G.F. High expression of the Met receptor in prostate cancer metastasis to bone.Urology20026061113111710.1016/S0090‑4295(02)01954‑412475693
     [Google Scholar]
  37. HumphreyP.A. ZhuX. ZarnegarR. SwansonP.E. RatliffT.L. VollmerR.T. DayM.L. Hepatocyte growth factor and its receptor (c-MET) in prostatic carcinoma.Am. J. Pathol.199514723863967639332
     [Google Scholar]
  38. VerrasM. LeeJ. XueH. LiT.H. WangY. SunZ. The androgen receptor negatively regulates the expression of c-Met: implications for a novel mechanism of prostate cancer progression.Cancer Res.200767396797510.1158/0008‑5472.CAN‑06‑355217283128
     [Google Scholar]
  39. De BaccoF. LuraghiP. MedicoE. ReatoG. GirolamiF. PereraT. GabrieleP. ComoglioP.M. BoccaccioC. Induction of MET by ionizing radiation and its role in radioresistance and invasive growth of cancer.J. Natl. Cancer Inst.2011103864566110.1093/jnci/djr09321464397
     [Google Scholar]
  40. LiS. ZhaoY. WangK. GaoY. HanJ. CuiB. GongP. 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.201321112843285510.1016/j.bmc.2013.04.01323628470
     [Google Scholar]
  41. KaragülleO.O. YurttaşA.G. Synergistic effects of ozone with doxorubicin on the proliferation, apoptosis and metastatic profile of luminal-B type human breast cancer cell line.Tissue Cell20238510223310.1016/j.tice.2023.10223337866151
     [Google Scholar]
  42. SaharkhizS. ZarepourA. NasriN. CordaniM. ZarrabiA. A comparison study between doxorubicin and curcumin co-administration and co-loading in a smart niosomal formulation for MCF-7 breast cancer therapy.Eur. J. Pharm. Sci.202319110660010.1016/j.ejps.2023.10660037802230
     [Google Scholar]
  43. SaharkhizS. ZarepourA. ZarrabiA. A new theranostic pH-responsive niosome formulation for doxorubicin delivery and bio-imaging against breast cancer.Int. J. Pharm.202363712284510.1016/j.ijpharm.2023.12284536958608
     [Google Scholar]
  44. HanX. AluA. LiuH. ShiY. WeiX. CaiL. WeiY. Biomaterial-assisted biotherapy: A brief review of biomaterials used in drug delivery, vaccine development, gene therapy, and stem cell therapy.Bioact. Mater.202217294810.1016/j.bioactmat.2022.01.01135386442
     [Google Scholar]
  45. MendietaI. Rodríguez-NietoM. Nuñez-AnitaR.E. Menchaca-ArredondoJ.L. García-AlcocerG. BerumenL.C. BerumenL.C. Ultrastructural changes associated to the neuroendocrine transdifferentiation of the lung adenocarcinoma cell line A549.Acta Histochem.2021123815179710.1016/j.acthis.2021.15179734688180
     [Google Scholar]
  46. GaoJ. ZhaoY. WangC. JiH. YuJ. LiuC. LiuA. A novel synthetic chitosan selenate (CS) induces apoptosis in A549 lung cancer cells via the Fas/FasL pathway.Int. J. Biol. Macromol.202015868969710.1016/j.ijbiomac.2020.05.01632387597
     [Google Scholar]
  47. NunhartP. KonkoľováE. JanovecL. JendželovskýR. VargováJ. ŠevcJ. MatejováM. MiltákováB. FedoročkoP. KozurkovaM. Fluorinated 3,6,9-trisubstituted acridine derivatives as DNA interacting agents and topoisomerase inhibitors with A549 antiproliferative activity.Bioorg. Chem.20209410339310.1016/j.bioorg.2019.10339331679839
     [Google Scholar]
  48. MoharebR.M. MukhtarS. ParveenH. AbdelazizM.A. AlwanE.S. Anti-proliferative, Morphological and Molecular docking studies of new thiophene derivatives and their strategy in ionic liquid immobilized reactions.Anticancer. Agents Med. Chem.202424969170810.2174/011871520626230723112210474838321904
     [Google Scholar]
/content/journals/acamc/10.2174/0118715206323592240909101754
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Synthesis of New Chromen-5-one Derivatives from Dimedone and their Antiproliferative Evaluations against Selected Cancer Cell Lines Together with Hepatocellular Carcinoma and Cervical Carcinoma
Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) 25, 134 (2025); https://doi.org/10.2174/0118715206323592240909101754
/content/journals/acamc/10.2174/0118715206323592240909101754
/content/journals/acamc/10.2174/0118715206323592240909101754
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  • Article Type:     Research Article
Keyword(s): Antiproliferative activity; chromen-5-one; Chromeno[5,6-d]thiazol; coumarin nuclei; cytotoxicity; morphology

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