Skip to content
2000
Volume 29, Issue 4
  • ISSN: 1385-2728
  • E-ISSN: 1875-5348

Abstract

A series of N-(substituted)-4-methyl aniline derivatives has been designed and synthesized, and their biological activities were also evaluated as potential anti-tumor and tubulin enzyme inhibitors. Among all compounds, compound showed the most potent tubulin aromatase enzyme inhibitory activity with an IC of 157.3 pg/mL compared to the reference inhibitor Dox (IC = 227.4 pg/mL). A docking simulation was performed to insert compound into the crystal structure of human aromatase at the active site to determine the probable binding model. Based on the previous results, compound with potent inhibitory activity on tumor growth could be employed as a potential anticancer agent.

Loading

Article metrics loading...

/content/journals/coc/10.2174/0113852728321140240811170956
2024-08-27
2025-01-18
Loading full text...

Full text loading...

References

  1. SalemM.G. Abu El-ataS.A. ElsayedE.H. MaliS.N. AlshwyehH.A. AlmaimaniG. AlmaimaniR.A. AlmasmoumH.A. AltwaijryN. Al-OlayanE. SaiedE.M. YoussefM.F. Novel 2-substituted-quinoxaline analogs with potential antiproliferative activity against breast cancer: Insights into cell cycle arrest, topoisomerase II, and EGFR activity.RSC Advances20231347330803309510.1039/D3RA06189B37954422
    [Google Scholar]
  2. ChenF. WendlM.C. WyczalkowskiM.A. BaileyM.H. LiY. DingL. Moving pan-cancer studies from basic research toward the clinic.Nat. Can.20212987989010.1038/s43018‑021‑00250‑435121865
    [Google Scholar]
  3. IslamM.S. RahiM.S. JahangirC.A. RahmanM.H. JerinI. AminR. HoqueK.M.F. RezaM.A. In vivo anticancer activity of Basella alba leaf and seed extracts against ehrlich’s ascites carcinoma (EAC) cell line.Evid. Based Complement. Alternat. Med.20182018153789610.1155/2018/1537896
    [Google Scholar]
  4. HolohanC. Van SchaeybroeckS. LongleyD.B. JohnstonP.G. Cancer drug resistance: An evolving paradigm.Nat. Rev. Cancer2013131071472610.1038/nrc359924060863
    [Google Scholar]
  5. MurphreeA.L. VillablancaJ.G. DeeganW.F. SatoJ.K. MalogolowkinM. FisherA. GomerC.J. Chemotherapy plus local treatment in the management of intraocular retinoblastoma.Arch. Ophthalmol.1996114111348135610.1001/archopht.1996.01100140548005
    [Google Scholar]
  6. GomtsyanA. Heterocycles in drugs and drug discovery.Chem. Heterocycl. Compd.201248171010.1007/s10593‑012‑0960‑z
    [Google Scholar]
  7. HoelderS. ClarkeP.A. WorkmanP. Discovery of small molecule cancer drugs: Successes, challenges and opportunities.Mol. Oncol.20126215517610.1016/j.molonc.2012.02.00422440008
    [Google Scholar]
  8. ZhangJ. YangP.L. GrayN.S. Targeting cancer with small molecule kinase inhibitors.Nat. Rev. Cancer200991283910.1038/nrc2559
    [Google Scholar]
  9. Ramos-InzaS. AydilloC. SanmartínC. PlanoD. Thiazole moiety: An interesting scaffold for developing new antitumoral compounds.In: Heterocycles - Synthesis and Biological Activities; IntechOpen2019
    [Google Scholar]
  10. WelschM.E. SnyderS.A. StockwellB.R. Privileged scaffolds for library design and drug discovery.Curr. Opin. Chem. Biol.201014334736110.1016/j.cbpa.2010.02.01820303320
    [Google Scholar]
  11. WaziriI. IsaM.A. SonopoM. WilliamsD.B.G. MullerA. Synthesis, anti-microbial, toxicity and molecular docking studies of N-nitroso-N-phenylhydroxylamine (cupferron) and its derivatives.Bioorg. Med. Chem. Lett.20215212838110.1016/j.bmcl.2021.12838134571137
    [Google Scholar]
  12. SrivastavaM. SinghJ. SinghS.B. TiwariK. PathakV.K. SinghJ. Synthesis of novel fused heterocycle-oxa-aza-phenanthrene and anthracene derivatives via sequential one-pot synthesis in aqueous micellar system.Green Chem.201214490190510.1039/c2gc16425f
    [Google Scholar]
  13. XieZ. ChenX. JiangG. FanQ. YangH. LeZ. Photocatalytic synthesis of 2,4‐substituted quinazolines via a one‐pot, three‐component reaction under catalyst‐free conditions.J. Heterocycl. Chem.202461694895410.1002/jhet.4810
    [Google Scholar]
  14. AroraS. NarayanP. OsgoodC.L. WedamS. ProwellT.M. GaoJ.J. ShahM. KrolD. WahbyS. RoyceM. GhoshS. PhilipR. IsonG. BermanT. BrusC. BloomquistE.W. FieroM.H. TangS. PazdurR. IbrahimA. Amiri-KordestaniL. BeaverJ.A.US. FDA drug approvals for breast cancer: A decade in review.Clin. Cancer Res.20222861072108610.1158/1078‑0432.CCR‑21‑260034711632
    [Google Scholar]
  15. AnJ. PengC. XieX. PengF. New advances in targeted therapy of HER2-negative breast cancer.Front. Oncol.20221282843810.3389/fonc.2022.82843835311116
    [Google Scholar]
  16. HermanowiczJ.M. SzymanowskaA. SiekluckaB. CzarnomysyR. PawlakK. BielawskaA. BielawskiK. KalafutJ. PrzybyszewskaA. SurazynskiA. Rivero-MullerA. MojzychM. PawlakD. Exploration of novel heterofused 1,2,4-triazine derivative in colorectal cancer.J. Enzyme Inhib. Med. Chem.202136153554810.1080/14756366.2021.187980333522320
    [Google Scholar]
  17. MouradA.A.E. RizzkY.W. ZakiI. MohammedF.Z. El BeheryM. Synthesis and cytotoxicity screening of some synthesized hybrid nitrogen molecules as anticancer agents.J. Mol. Struct.2021124213072210.1016/j.molstruc.2021.130722
    [Google Scholar]
  18. LeeC.C. ShihY.S. WuC.S. TsaiC.H. YehS.T. PengY.H. ChenK.J. Development of robust flexible OLED encapsulations using simulated estimations and experimental validations.J. Phys. D Appl. Phys.2012452727510210.1088/0022‑3727/45/27/275102
    [Google Scholar]
  19. KourouK. ManikisG. MylonaE. Poikonen-SakselaP. MazzoccoK. Pat-HorenczykR. SousaB. Oliveira-MaiaA.J. MattsonJ. RozinerI. PettiniG. KondylakisH. MariasK. NuutinenM. KarademasE. SimosP. FotiadisD.I. Personalized prediction of one-year mental health deterioration using adaptive learning algorithms: A multicenter breast cancer prospective study.Sci. Rep.2023131705910.1038/s41598‑023‑33281‑137120428
    [Google Scholar]
  20. MohammedF.Z. RizzkY.W. El-DeenI.M. GadE.M. El BeheryM. MahdyA.R.E. Discovery of 2‐Amino‐4H‐1, 3, 4‐thiadiazine‐5(6H)‐one derivatives and their in vitro antitumor investigation.ChemistrySelect202277e20210433310.1002/slct.202104333
    [Google Scholar]
  21. GhoshD. EgbutaC. LoJ. Testosterone complex and non-steroidal ligands of human aromatase.J. Steroid Biochem. Mol. Biol.2018181111910.1016/j.jsbmb.2018.02.00929476820
    [Google Scholar]
  22. ZakiI. AbdelhameidM.K. El-DeenI.M. Abdel WahabA.H.A. AshmawyA.M. MohamedK.O. Design, synthesis and screening of 1, 2, 4-triazinone derivatives as potential antitumor agents with apoptosis inducing activity on MCF-7 breast cancer cell line.Eur. J. Med. Chem.201815656357910.1016/j.ejmech.2018.07.00330025350
    [Google Scholar]
  23. BlackburnH.L. EllsworthD.L. ShriverC.D. EllsworthR.E. Role of cytochrome P450 genes in breast cancer etiology and treatment: effects on estrogen biosynthesis, metabolism, and response to endocrine therapy.Cancer Causes Control201526331933210.1007/s10552‑014‑0519‑725554091
    [Google Scholar]
  24. MohamedF.Z. RizzkY.W. Design, synthesis, cytotoxic screening and molecular docking studies of novel hybrid thiosemicarbazone derivatives as anticancer agents.Chem. Biodivers.20211812e210058010.1002/cbav.202100580
    [Google Scholar]
  25. KheirollahiA. PordeliM. SafaviM. MashkouriS. Naimi-JamalM.R. ArdestaniS.K. Cytotoxic and apoptotic effects of synthetic benzochromene derivatives on human cancer cell lines.Naunyn Schmiedebergs Arch. Pharmacol.2014387121199120810.1007/s00210‑014‑1038‑525261336
    [Google Scholar]
  26. ThomsenR. ChristensenM.H. MolDock: A new technique for high-accuracy molecular docking.J. Med. Chem.200649113315332110.1021/jm051197e16722650
    [Google Scholar]
  27. ButtiR. DasS. GunasekaranV.P. YadavA.S. KumarD. KunduG.C. Receptor tyrosine kinases (RTKs) in breast cancer: Signaling, therapeutic implications and challenges.Mol. Cancer2018171118
    [Google Scholar]
  28. TongL. WarrenT.C. KingJ. BetageriR. RoseJ. JakesS. Crystal structures of the human p56lck SH2 domain in complex with two short phosphotyrosyl peptides at 1.0 A and 1.8 A resolution.J. Mol. Biol.1996256360161010.1006/jmbi.1996.01128604142
    [Google Scholar]
  29. BeheryM.E. El-DeenI.M. El-ZendM.A. BarakatL.A.A. Design, synthesis and evaluation the bioactivities of novel 8 methoxy-1-azacoumarin-3-carboxamide derivatives as anti-diabetic agents.J. Mol. Struct.2023129413648610.1016/j.molstruc.2023.136486
    [Google Scholar]
  30. El-ZendM.A. TantawyM.A. BarakatL.A.A. BarakatL.A. Synthesis and cytotoxicity screening of some synthesized coumarin and aza-coumarin derivatives as anticancer agents.Russ. J. Bioorganic Chem.202248238039010.1134/S106816202202011X
    [Google Scholar]
  31. Ali BarakatL.A. El-DeenI.M. El-ZendM.A. El-BeheryM. In vitro cytotoxic investigation of some synthesized 1,6-disubstituted-1-azacoumarin derivatives as anticancer agents.Future Med. Chem.202315242289230710.4155/fmc‑2023‑026038047384
    [Google Scholar]
/content/journals/coc/10.2174/0113852728321140240811170956
Loading
/content/journals/coc/10.2174/0113852728321140240811170956
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher’s website along with the published article.

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