Skip to content
2000
Volume 25, Issue 5
  • ISSN: 1568-0266
  • E-ISSN: 1873-4294

Abstract

Cancer continues to be a major global health challenge, driving the need for the discovery of novel therapeutic agents. Among these, heterocyclic phytochemicals have gained significant attention for their potential as anticancer agents. This review offers a detailed analysis of various classes of heterocyclic compounds with proven anticancer properties, shedding light on their mechanisms of action. The study draws from a diverse array of natural product sources, detailing the chemical structures and bioactivities of these compounds. Key heterocyclic classes such as alkaloids, flavonoids, coumarins, and terpenoids are emphasized due to their potent anticancer effects. Heterocyclic phytochemicals exhibit diverse anticancer mechanisms, including the modulation of cellular pathways like apoptosis, angiogenesis, and cell cycle progression. The combination of heterocyclic phytochemicals with conventional cancer therapies has shown promising synergistic effects, enhanced treatment efficacy and reducing side effects. The review systematically evaluates both preclinical and clinical studies, revealing the efficacy, safety profiles, and pharmacokinetics of selected heterocyclic compounds. The promising outcomes highlighted in this review underscore the critical need for ongoing research to fully realize the therapeutic potential of heterocyclic phytochemicals in cancer treatment.

Loading

Article metrics loading...

/content/journals/ctmc/10.2174/0115680266314693240914070250
2024-09-27
2025-04-13
Loading full text...

Full text loading...

References

  1. MartinsP. JesusJ. SantosS. RaposoL. Roma-RodriguesC. BaptistaP. FernandesA. Heterocyclic anticancer compounds: Recent advances and the paradigm shift towards the use of nanomedicine’s tool box.Molecules2015209168521689110.3390/molecules200916852 26389876
    [Google Scholar]
  2. SachdevaH. KhaturiaS. SaquibM. KhatikN. KhandelwalA.R. MeenaR. SharmaK. Oxygen-and sulphur-containing heterocyclic compounds as potential anticancer agents.Appl. Biochem. Biotechnol.2022194126438646710.1007/s12010‑022‑04099‑w 35900713
    [Google Scholar]
  3. AlrooqiM. KhanS. AlhumaydhiF.A. AsiriS.A. AlshamraniM. MashraqiM.M. AlzamamiA. AlshahraniA.M. AldahishA.A. A therapeutic journey of pyridine-based heterocyclic compounds as potent anticancer agents: A review.Anticancer. Agents Med. Chem.202222152775278710.2174/1871520622666220324102849 35331100
    [Google Scholar]
  4. MansD.R.A. RochaA.B. SchwartsmannG. Anti-cancer drug discovery and development in Brazil: Targeted plant collection as a rational strategy to acquire candidate anti-cancer compounds.Oncologist20005318519810.1634/theoncologist.5‑3‑185 10884497
    [Google Scholar]
  5. TandonR. SinghI. LuxamiV. TandonN. PaulK. Recent advances and developments of in vitro evaluation of heterocyclic moieties on cancer cell lines.Chem. Rec.2019192-336239310.1002/tcr.201800024 29943894
    [Google Scholar]
  6. KocarnikJ.M. ComptonK. DeanF.E. FuW. GawB.L. HarveyJ.D. HenriksonH.J. LuD. PenniniA. XuR. AbabnehE. Abbasi-KangevariM. AbbastabarH. Abd-ElsalamS.M. AbdoliA. AbediA. AbidiH. AbolhassaniH. AdedejiI.A. AdnaniQ.E.S. AdvaniS.M. AfzalM.S. AghaaliM. AhinkorahB.O. AhmadS. AhmadT. AhmadiA. AhmadiS. Ahmed RashidT. Ahmed SalihY. AkaluG.T. AkliluA. AkramT. AkunnaC.J. Al HamadH. AlahdabF. Al-AlyZ. AliS. AlimohamadiY. AlipourV. AljunidS.M. AlkhayyatM. Almasi-HashianiA. AlmasriN.A. Al-MaweriS.A.A. AlmustanyirS. AlonsoN. Alvis-GuzmanN. AmuH. AnbesuE.W. AncuceanuR. AnsariF. Ansari-MoghaddamA. AntwiM.H. AnvariD. AnyasodorA.E. AqeelM. ArablooJ. Arab-ZozaniM. AremuO. AriffinH. AripovT. ArshadM. ArtamanA. ArulappanJ. AsemiZ. Asghari JafarabadiM. AshrafT. AtorkeyP. AujayebA. AusloosM. AwedewA.F. Ayala QuintanillaB.P. AyenewT. AzabM.A. AzadnajafabadS. Azari JafariA. AzarianG. AzzamA.Y. BadiyeA.D. BahadoryS. BaigA.A. BakerJ.L. BalakrishnanS. BanachM. BärnighausenT.W. Barone-AdesiF. BarraF. BarrowA. BehzadifarM. BelgaumiU.I. BezabheW.M.M. BezabihY.M. BhagatD.S. BhagavathulaA.S. BhardwajN. BhardwajP. BhaskarS. BhattacharyyaK. BhojarajaV.S. BibiS. BijaniA. BiondiA. BisignanoC. BjørgeT. BleyerA. BlyussO. BolarinwaO.A. BollaS.R. BraithwaiteD. BrarA. BrennerH. Bustamante-TeixeiraM.T. ButtN.S. ButtZ.A. Caetano dos SantosF.L. CaoY. CarrerasG. Catalá-LópezF. CembranelF. CerinE. CernigliaroA. ChakinalaR.C. ChattuS.K. ChattuV.K. ChaturvediP. Chimed-OchirO. ChoD.Y. ChristopherD.J. ChuD.T. ChungM.T. CondeJ. CortésS. CortesiP.A. CostaV.M. CunhaA.R. DadrasO. DagnewA.B. DahlawiS.M.A. DaiX. DandonaL. DandonaR. DarweshA.M. das Neves, J.; De la Hoz, F.P.; Demis, A.B.; Denova-Gutiérrez, E.; Dhamnetiya, D.; Dhimal, M.L.; Dhimal, M.; Dianatinasab, M.; Diaz, D.; Djalalinia, S.; Do, H.P.; Doaei, S.; Dorostkar, F.; dos Santos Figueiredo, F.W.; Driscoll, T.R.; Ebrahimi, H.; Eftekharzadeh, S.; El Tantawi, M.; El-Abid, H.; Elbarazi, I.; Elhabashy, H.R.; Elhadi, M.; El-Jaafary, S.I.; Eshrati, B.; Eskandarieh, S.; Esmaeilzadeh, F.; Etemadi, A.; Ezzikouri, S.; Faisaluddin, M.; Faraon, E.J.A.; Fares, J.; Farzadfar, F.; Feroze, A.H.; Ferrero, S.; Ferro Desideri, L.; Filip, I.; Fischer, F.; Fisher, J.L.; Foroutan, M.; Fukumoto, T.; Gaal, P.A.; Gad, M.M.; Gadanya, M.A.; Gallus, S.; Gaspar Fonseca, M.; Getachew Obsa, A.; Ghafourifard, M.; Ghashghaee, A.; Ghith, N.; Gholamalizadeh, M.; Gilani, S.A.; Ginindza, T.G.; Gizaw, A.T.T.; Glasbey, J.C.; Golechha, M.; Goleij, P.; Gomez, R.S.; Gopalani, S.V.; Gorini, G.; Goudarzi, H.; Grosso, G.; Gubari, M.I.M.; Guerra, M.R.; Guha, A.; Gunasekera, D.S.; Gupta, B.; Gupta, V.B.; Gupta, V.K.; Gutiérrez, R.A.; Hafezi-Nejad, N.; Haider, M.R.; Haj-Mirzaian, A.; Halwani, R.; Hamadeh, R.R.; Hameed, S.; Hamidi, S.; Hanif, A.; Haque, S.; Harlianto, N.I.; Haro, J.M.; Hasaballah, A.I.; Hassanipour, S.; Hay, R.J.; Hay, S.I.; Hayat, K.; Heidari, G.; Heidari, M.; Herrera-Serna, B.Y.; Herteliu, C.; Hezam, K.; Holla, R.; Hossain, M.M.; Hossain, M.B.H.; Hosseini, M.S.; Hosseini, M.; Hosseinzadeh, M.; Hostiuc, M.; Hostiuc, S.; Househ, M.; Hsairi, M.; Huang, J.; Hugo, F.N.; Hussain, R.; Hussein, N.R.; Hwang, B.F.; Iavicoli, I.; Ibitoye, S.E.; Ida, F.; Ikuta, K.S.; Ilesanmi, O.S.; Ilic, I.M.; Ilic, M.D.; Irham, L.M.; Islam, J.Y.; Islam, R.M.; Islam, S.M.S.; Ismail, N.E.; Isola, G.; Iwagami, M.; Jacob, L.; Jain, V.; Jakovljevic, M.B.; Javaheri, T.; Jayaram, S.; Jazayeri, S.B.; Jha, R.P.; Jonas, J.B.; Joo, T.; Joseph, N.; Joukar, F.; Jürisson, M.; Kabir, A.; Kahrizi, D.; Kalankesh, L.R.; Kalhor, R.; Kaliyadan, F.; Kalkonde, Y.; Kamath, A.; Kameran Al-Salihi, N.; Kandel, H.; Kapoor, N.; Karch, A.; Kasa, A.S.; Katikireddi, S.V.; Kauppila, J.H.; Kavetskyy, T.; Kebede, S.A.; Keshavarz, P.; Keykhaei, M.; Khader, Y.S.; Khalilov, R.; Khan, G.; Khan, M.; Khan, M.N.; Khan, M.A.B.; Khang, Y.H.; Khater, A.M.; Khayamzadeh, M.; Kim, G.R.; Kim, Y.J.; Kisa, A.; Kisa, S.; Kissimova-Skarbek, K.; Kopec, J.A.; Koteeswaran, R.; Koul, P.A.; Koulmane Laxminarayana, S.L.; Koyanagi, A.; Kucuk Bicer, B.; Kugbey, N.; Kumar, G.A.; Kumar, N.; Kumar, N.; Kurmi, O.P.; Kutluk, T.; La Vecchia, C.; Lami, F.H.; Landires, I.; Lauriola, P.; Lee, S.; Lee, S.W.H.; Lee, W.C.; Lee, Y.H.; Leigh, J.; Leong, E.; Li, J.; Li, M.C.; Liu, X.; Loureiro, J.A.; Lunevicius, R.; Magdy Abd El Razek, M.; Majeed, A.; Makki, A.; Male, S.; Malik, A.A.; Mansournia, M.A.; Martini, S.; Masoumi, S.Z.; Mathur, P.; McKee, M.; Mehrotra, R.; Mendoza, W.; Menezes, R.G.; Mengesha, E.W.; Mesregah, M.K.; Mestrovic, T.; Miao Jonasson, J.; Miazgowski, B.; Miazgowski, T.; Michalek, I.M.; Miller, T.R.; Mirzaei, H.; Mirzaei, H.R.; Misra, S.; Mithra, P.; Moghadaszadeh, M.; Mohammad, K.A.; Mohammad, Y.; Mohammadi, M.; Mohammadi, S.M.; Mohammadian-Hafshejani, A.; Mohammed, S.; Moka, N.; Mokdad, A.H.; Molokhia, M.; Monasta, L.; Moni, M.A.; Moosavi, M.A.; Moradi, Y.; Moraga, P.; Morgado-da-Costa, J.; Morrison, S.D.; Mosapour, A.; Mubarik, S.; Mwanri, L.; Nagarajan, A.J.; Nagaraju, S.P.; Nagata, C.; Naimzada, M.D.; Nangia, V.; Naqvi, A.A.; Narasimha Swamy, S.; Ndejjo, R.; Nduaguba, S.O.; Negoi, I.; Negru, S.M.; Neupane Kandel, S.; Nguyen, C.T.; Nguyen, H.L.T.; Niazi, R.K.; Nnaji, C.A.; Noor, N.M.; Nuñez-Samudio, V.; Nzoputam, C.I.; Oancea, B.; Ochir, C.; Odukoya, O.O.; Ogbo, F.A.; Olagunju, A.T.; Olakunde, B.O.; Omar, E.; Omar Bali, A.; Omonisi, A.E.E.; Ong, S.; Onwujekwe, O.E.; Orru, H.; Ortega-Altamirano, D.V.; Otstavnov, N.; Otstavnov, S.S.; Owolabi, M.O.; P A, M.; Padubidri, J.R.; Pakshir, K.; Pana, A.; Panagiotakos, D.; Panda-Jonas, S.; Pardhan, S.; Park, E.C.; Park, E.K.; Pashazadeh Kan, F.; Patel, H.K.; Patel, J.R.; Pati, S.; Pattanshetty, S.M.; Paudel, U.; Pereira, D.M.; Pereira, R.B.; Perianayagam, A.; Pillay, J.D.; Pirouzpanah, S.; Pishgar, F.; Podder, I.; Postma, M.J.; Pourjafar, H.; Prashant, A.; Preotescu, L.; Rabiee, M.; Rabiee, N.; Radfar, A.; Radhakrishnan, R.A.; Radhakrishnan, V.; Rafiee, A.; Rahim, F.; Rahimzadeh, S.; Rahman, M.; Rahman, M.A.; Rahmani, A.M.; Rajai, N.; Rajesh, A.; Rakovac, I.; Ram, P.; Ramezanzadeh, K.; Ranabhat, K.; Ranasinghe, P.; Rao, C.R.; Rao, S.J.; Rawassizadeh, R.; Razeghinia, M.S.; Renzaho, A.M.N.; Rezaei, N.; Rezaei, N.; Rezapour, A.; Roberts, T.J.; Rodriguez, J.A.B.; Rohloff, P.; Romoli, M.; Ronfani, L.; Roshandel, G.; Rwegerera, G.M.; S, M.; Sabour, S.; Saddik, B.; Saeed, U.; Sahebkar, A.; Sahoo, H.; Salehi, S.; Salem, M.R.; Salimzadeh, H.; Samaei, M.; Samy, A.M.; Sanabria, J.; Sankararaman, S.; Santric-Milicevic, M.M.; Sardiwalla, Y.; Sarveazad, A.; Sathian, B.; Sawhney, M.; Saylan, M.; Schneider, I.J.C.; Sekerija, M.; Seylani, A.; Shafaat, O.; Shaghaghi, Z.; Shaikh, M.A.; Shamsoddin, E.; Shannawaz, M.; Sharma, R.; Sheikh, A.; Sheikhbahaei, S.; Shetty, A.; Shetty, J.K.; Shetty, P.H.; Shibuya, K.; Shirkoohi, R.; Shivakumar, K.M.; Shivarov, V.; Siabani, S.; Siddappa Malleshappa, S.K.; Silva, D.A.S.; Singh, J.A.; Sintayehu, Y.; Skryabin, V.Y.; Skryabina, A.A.; Soeberg, M.J.; Sofi-Mahmudi, A.; Sotoudeh, H.; Steiropoulos, P.; Straif, K.; Subedi, R.; Sufiyan, M.B.; Sultan, I.; Sultana, S.; Sur, D.; Szerencsés, V.; Szócska, M.; Tabarés-Seisdedos, R.; Tabuchi, T.; Tadbiri, H.; Taherkhani, A.; Takahashi, K.; Talaat, I.M.; Tan, K.K.; Tat, V.Y.; Tedla, B.A.A.; Tefera, Y.G.; Tehrani-Banihashemi, A.; Temsah, M.H.; Tesfay, F.H.; Tessema, G.A.; Thapar, R.; Thavamani, A.; Thoguluva Chandrasekar, V.; Thomas, N.; Tohidinik, H.R.; Touvier, M.; Tovani-Palone, M.R.; Traini, E.; Tran, B.X.; Tran, K.B.; Tran, M.T.N.; Tripathy, J.P.; Tusa, B.S.; Ullah, I.; Ullah, S.; Umapathi, K.K.; Unnikrishnan, B.; Upadhyay, E.; Vacante, M.; Vaezi, M.; Valadan Tahbaz, S.; Velazquez, D.Z.; Veroux, M.; Violante, F.S.; Vlassov, V.; Vo, B.; Volovici, V.; Vu, G.T.; Waheed, Y.; Wamai, R.G.; Ward, P.; Wen, Y.F.; Westerman, R.; Winkler, A.S.; Yadav, L.; Yahyazadeh Jabbari, S.H.; Yang, L.; Yaya, S.; Yazie, T.S.Y.; Yeshaw, Y.; Yonemoto, N.; Younis, M.Z.; Yousefi, Z.; Yu, C.; Yuce, D.; Yunusa, I.; Zadnik, V.; Zare, F.; Zastrozhin, M.S.; Zastrozhina, A.; Zhang, J.; Zhong, C.; Zhou, L.; Zhu, C.; Ziapour, A.; Zimmermann, I.R.; Fitzmaurice, C.; Murray, C.J.L.; Force, L.M. Cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life years for 29 cancer groups from 2010 to 2019: A systematic analysis for the global burden of disease study (2019).JAMA Oncol.20228342044410.1001/jamaoncol.2021.6987 34967848
    [Google Scholar]
  7. DaiJ. AshrafizadehM. ArefA.R. SethiG. ErtasY.N. Peptide-functionalized, -assembled and -loaded nanoparticles in cancer therapy.Drug Discov. Today202429710398110.1016/j.drudis.2024.103981 38614161
    [Google Scholar]
  8. LangD.K. KaurR. AroraR. SainiB. AroraS. Nitrogen-containing heterocycles as anticancer agents: An overview.Anticancer. Agents Med. Chem.202020182150216810.2174/1871520620666200705214917 32628593
    [Google Scholar]
  9. HeraviM.M. ZadsirjanV. Prescribed drugs containing nitrogen heterocycles: An overview.RSC Advances20201072442474431110.1039/D0RA09198G 35557843
    [Google Scholar]
  10. YuanS. LuoY.Q. ZuoJ.H. LiuH. LiF. YuB. New drug approvals for 2020: Synthesis and clinical applications.Eur. J. Med. Chem.202121511328410.1016/j.ejmech.2021.113284 33611190
    [Google Scholar]
  11. LeeM.M.L. ChanB.D. WongW.Y. LeungT.W. QuZ. HuangJ. ZhuL. LeeC.S. ChenS. TaiW.C.S. Synthesis and evaluation of novel anticancer compounds derived from the natural product Brevilin A.ACS Omega2020524145861459610.1021/acsomega.0c01276 32596596
    [Google Scholar]
  12. PerksC.M. KeithA.J. GoodhewK.L. SavageP.B. WintersZ.E. HollyJ.M.P. Prolactin acts as a potent survival factor for human breast cancer cell lines.Br. J. Cancer200491230531110.1038/sj.bjc.6601947 15213724
    [Google Scholar]
  13. KnektP. JärvinenR. SeppänenR. HellövaaraM. TeppoL. Dietary flavonoids and the risk of lung cancer and other malignant neoplasms.Am. J. Epidemiol.1997146322323010.1093/oxfordjournals.aje.a009257
    [Google Scholar]
  14. HertogM.G.L. FeskensE.J.M. HollmanP.C.H. KatanM.B. KromhoutD. Dietary flavonoids and cancer risk in the Zutphen elderly study.Nutr. Cancer199422217518410.1080/01635589409514342 14502846
    [Google Scholar]
  15. ShuklaS. GuptaS. Apigenin: A promising molecule for cancer prevention.Pharm. Res.201027696297810.1007/s11095‑010‑0089‑7 20306120
    [Google Scholar]
  16. NguyenT.B. LozachO. SurpateanuG. WangQ. RetailleauP. IorgaB.I. MeijerL. GuéritteF. Synthesis, biological evaluation, and molecular modeling of natural and unnatural flavonoidal alkaloids, inhibitors of kinases.J. Med. Chem.20125562811281910.1021/jm201727w 22352892
    [Google Scholar]
  17. RajeN. HideshimaT. MukherjeeS. RaabM. ValletS. ChhetriS. CirsteaD. PozziS. MitsiadesC. RooneyM. KiziltepeT. PodarK. OkawaY. IkedaH. CarrascoR. RichardsonP.G. ChauhanD. MunshiN.C. SharmaS. ParikhH. ChabnerB. ScaddenD. AndersonK.C. Preclinical activity of P276-00, a novel small-molecule cyclin-dependent kinase inhibitor in the therapy of multiple myeloma.Leukemia200923596197010.1038/leu.2008.378 19151776
    [Google Scholar]
  18. ParkW.H. MAPK inhibitors differentially affect gallic acid-induced human pulmonary fibroblast cell growth inhibition.Mol. Med. Rep.20114119304 21461585
    [Google Scholar]
  19. CavalliA. BisiA. BertucciC. RosiniC. PaluszcakA. GobbiS. GiorgioE. RampaA. BellutiF. PiazziL. ValentiP. HartmannR.W. RecanatiniM. Enantioselective nonsteroidal aromatase inhibitors identified through a multidisciplinary medicinal chemistry approach.J. Med. Chem.200548237282728910.1021/jm058042r 16279787
    [Google Scholar]
  20. YaoN. ChenC.Y. WuC.Y. MotonishiK. KungH.J. LamK.S. Novel flavonoids with antiproliferative activities against breast cancer cells.J. Med. Chem.201154134339434910.1021/jm101440r 21599001
    [Google Scholar]
  21. MahapatraD.K. BhartiS.K. AsatiV. Anti-cancer chalcones: Structural and molecular target perspectives.Eur. J. Med. Chem.2015986911410.1016/j.ejmech.2015.05.004 26005917
    [Google Scholar]
  22. LiuY. LuoJ. PengL. ZhangQ. RongX. LuoY. LiJ. Flavonoids: Potential therapeutic agents for cardiovascular disease.Heliyon20241012e3256310.1016/j.heliyon.2024.e32563 38975137
    [Google Scholar]
  23. WinterE. Devantier NeuenfeldtP. Chiaradia-DelatorreL.D. GauthierC. YunesR.A. NunesR.J. Creczynski-PasaT.B. Di PietroA. Symmetric bis-chalcones as a new type of breast cancer resistance protein inhibitors with a mechanism different from that of chromones.J. Med. Chem.20145772930294110.1021/jm401879z 24611893
    [Google Scholar]
  24. RangelL.P. WinterE. GauthierC. TerreuxR. Chiaradia-DelatorreL.D. MascarelloA. NunesR.J. YunesR.A. Creczynski-PasaT.B. MacalouS. LorendeauD. Baubichon-CortayH. Ferreira-PereiraA. Di PietroA. New structure-activity relationships of chalcone inhibitors of breast cancer resistance protein: polyspecificity toward inhibition and critical substitutions against cytotoxicity.Drug Des. Devel. Ther.2013710431052 24109177
    [Google Scholar]
  25. JuvaleK. PapeV.F.S. WieseM. Investigation of chalcones and benzochalcones as inhibitors of breast cancer resistance protein.Bioorg. Med. Chem.201220134635510.1016/j.bmc.2011.10.074 22112540
    [Google Scholar]
  26. MaalikiD. ShaitoA.A. PintusG. El-YazbiA. EidA.H. Flavonoids in hypertension: A brief review of the underlying mechanisms.Curr. Opin. Pharmacol.201945576510.1016/j.coph.2019.04.014 31102958
    [Google Scholar]
  27. MithöferA. BolandW. Plant defense against herbivores: Chemical aspects.Annu. Rev. Plant Biol.201263143145010.1146/annurev‑arplant‑042110‑103854 22404468
    [Google Scholar]
  28. ZenkM.H. JuengerM. Evolution and current status of the phytochemistry of nitrogenous compounds.Phytochemistry20076822-242757277210.1016/j.phytochem.2007.07.009 17719615
    [Google Scholar]
  29. AmewuR.K. SakyiP.O. Osei-SafoD. Addae-MensahI. Synthetic and naturally occurring heterocyclic anticancer compounds with multiple biological targets.Molecules20212623713410.3390/molecules26237134
    [Google Scholar]
  30. LouC. YokoyamaS. SaikiI. HayakawaY. Selective anticancer activity of hirsutine against HER2-positive breast cancer cells by inducing DNA damage.Oncol. Rep.20153342072207610.3892/or.2015.3796 25672479
    [Google Scholar]
  31. ShihY.W. ShiehJ.M. WuP.F. LeeY.C. ChenY.Z. ChiangT.A. α-Tomatine inactivates PI3K/Akt and ERK signaling pathways in human lung adenocarcinoma A549 cells: Effect on metastasis.Food Chem. Toxicol.20094781985199510.1016/j.fct.2009.05.011 19457446
    [Google Scholar]
  32. LiewS.Y. LooiC.Y. PaydarM. CheahF.K. LeongK.H. WongW.F. MustafaM.R. LitaudonM. AwangK. Subditine, a new monoterpenoid indole alkaloid from bark of Nauclea subdita (Korth.) Steud. induces apoptosis in human prostate cancer cells.PLoS One201492e8728610.1371/journal.pone.0087286 24551054
    [Google Scholar]
  33. YinY. XuJ. IlyasI. XuS. Bioactive flavonoids in protecting against endothelial dysfunction and atherosclerosis. In: Handbook of Experimental Pharmacology; Springer: Berlin, Heidelberg202410.1007/164_2024_715 38755351
    [Google Scholar]
  34. DevrieseL.A. WitteveenP.E.O. Mergui-RoelvinkM. SmithD.A. LewisL.D. MendelsonD.S. BangY.J. ChungH.C. DarM.M. HuitemaA.D.R. BeijnenJ.H. VoestE.E. SchellensJ.H.M. Pharmacodynamics and pharmacokinetics of oral topotecan in patients with advanced solid tumours and impaired renal function.Br. J. Clin. Pharmacol.201580225326610.1111/bcp.12606 25677219
    [Google Scholar]
  35. SinghM. SharmaP. SinghP.K. SinghT.G. SainiB. Medicinal potential of heterocyclic compounds from diverse natural sources for the management of cancer.Mini Rev. Med. Chem.2020201194295710.2174/1389557520666200212104742 32048967
    [Google Scholar]
  36. FardounM. IratniR. DehainiH. EidA. GhaddarT. El-ElimatT. AlaliF. BadranA. EidA.H. BaydounE. 7-O-methylpunctatin, a novel homoisoflavonoid, inhibits phenotypic switch of human arteriolar smooth muscle cells.Biomolecules201991171610.3390/biom9110716 31717401
    [Google Scholar]
  37. DeBonoA. CapuanoB. ScammellsP.J. Progress toward the development of noscapine and derivatives as anticancer agents.J. Med. Chem.201558155699572710.1021/jm501180v 25811651
    [Google Scholar]
  38. UcheF.I. DrijfhoutF.P. McCullaghJ. RichardsonA. LiW.W. Cytotoxicity effects and apoptosis induction by bisbenzylisoquinoline alkaloids from Triclisia subcordata.Phytother. Res.20163091533153910.1002/ptr.5660 27270992
    [Google Scholar]
  39. LaryeaD. IsakssonA. WrightC.W. LarssonR. NygrenP. Characterization of the cytotoxic activity of the indoloquinoline alkaloid cryptolepine in human tumour cell lines and primary cultures of tumour cells from patients.Invest. New Drugs200927540241110.1007/s10637‑008‑9185‑5 18853102
    [Google Scholar]
  40. ZhengL. WangX. LuoW. ZhanY. ZhangY. Brucine, an effective natural compound derived from nux-vomica, induces G1 phase arrest and apoptosis in LoVo cells.Food Chem. Toxicol.20135833233910.1016/j.fct.2013.05.011 23688861
    [Google Scholar]
  41. SlikaH. MansourH. WehbeN. NasserS.A. IratniR. NasrallahG. ShaitoA. GhaddarT. KobeissyF. EidA.H. Therapeutic potential of flavonoids in cancer: ROS-mediated mechanisms.Biomed. Pharmacother.202214611244210.1016/j.biopha.2021.112442 35062053
    [Google Scholar]
  42. AwadA.B. ChenY.C. FinkC.S. HennesseyT. beta-Sitosterol inhibits HT-29 human colon cancer cell growth and alters membrane lipids.Anticancer Res.1996165A27972804 8917388
    [Google Scholar]
  43. RashidM. ShrivastavaN. HusainA. Synthesis and SAR Strategy of Thiazolidinedione: A Novel Approach for Cancer Treatment.J. Chil. Chem. Soc.20206524817483210.4067/S0717‑97072020000204817
    [Google Scholar]
  44. AbdelsalamM.A. AboulWafa, O.M.; Badawey, E.S.A.M.; El-Shoukrofy, M.S.; El-Miligy, M.M.; Gouda, N. Design and synthesis of some β-carboline derivatives as multi-target anticancer agents.Future Med. Chem.201810242791281410.4155/fmc‑2018‑0226 30539666
    [Google Scholar]
  45. JiangY. LiX. LiX. HouJ. DingY. ZhangJ. XuW. ZhangY. Discovery of multi-target anticancer agents based on HDAC inhibitor MS-275 and 5-FU.Med. Chem.2016121303610.2174/1573406411666150714111045 26711240
    [Google Scholar]
  46. RibattiD. Judah Folkman, a pioneer in the study of angiogenesis.Angiogenesis200811131010.1007/s10456‑008‑9092‑6 18247146
    [Google Scholar]
  47. GuanX.W. XuX.H. FengS.L. TangZ.B. ChenS.W. HuiL. Synthesis of hybrid 4-deoxypodophyllotoxin–5-fluorouracil compounds that inhibit cellular migration and induce cell cycle arrest.Bioorg. Med. Chem. Lett.20162661561156610.1016/j.bmcl.2016.02.013 26873416
    [Google Scholar]
  48. PengF.W. XuanJ. WuT.T. XueJ.Y. RenZ.W. LiuD.K. WangX.Q. ChenX.H. ZhangJ.W. XuY.G. ShiL. Design, synthesis and biological evaluation of N-phenylquinazolin-4-amine hybrids as dual inhibitors of VEGFR-2 and HDAC.Eur. J. Med. Chem.201610911210.1016/j.ejmech.2015.12.033 26741358
    [Google Scholar]
  49. PunganuruS.R. MadalaH.R. VenugopalS.N. SamalaR. MikelisC. SrivenugopalK.S. Design and synthesis of a C7-aryl piperlongumine derivative with potent antimicrotubule and mutant p53-reactivating properties.Eur. J. Med. Chem.201610723324410.1016/j.ejmech.2015.10.052 26599530
    [Google Scholar]
  50. DragovichT. LaheruD. DayyaniF. BolejackV. SmithL. SengJ. BurrisH. RosenP. HidalgoM. RitchP. BakerA.F. RaghunandN. CrowleyJ. Von HoffD.D. Phase II trial of vatalanib in patients with advanced or metastatic pancreatic adenocarcinoma after first-line gemcitabine therapy (PCRT O4-001).Cancer Chemother. Pharmacol.201474237938710.1007/s00280‑014‑2499‑4 24939212
    [Google Scholar]
  51. RomeroA.H. SojoF. ArveloF. CalderónC. MoralesA. LópezS.E. Anticancer potential of new 3-nitroaryl-6-(N-methyl)piperazin-1,2,4-triazolo[3,4-a]phthalazines targeting voltage-gated K+ channel: Copper-catalyzed one-pot synthesis from 4-chloro-1-phthalazinyl-arylhydrazones.Bioorg. Chem.202010110403110.1016/j.bioorg.2020.104031 32629281
    [Google Scholar]
  52. ÖzdenS. AtabeyD. YıldızS. GökerH. Synthesis and potent antimicrobial activity of some novel methyl or ethyl 1H-benzimidazole-5-carboxylates derivatives carrying amide or amidine groups.Bioorg. Med. Chem.20051351587159710.1016/j.bmc.2004.12.025 15698776
    [Google Scholar]
  53. Romero-CastroA. León-RiveraI. Ávila-RojasL.C. Navarrete-VázquezG. Nieto-RodríguezA. Synthesis and preliminary evaluation of selected 2-aryl-5(6)-nitro- 1H-benzimidazole derivatives as potential anticancer agents.Arch. Pharm. Res.201134218118910.1007/s12272‑011‑0201‑5 21380799
    [Google Scholar]
  54. SukF.M. LiuC.L. HsuM.H. ChuangY.T. WangJ.P. LiaoY.J. Treatment with a new benzimidazole derivative bearing a pyrrolidine side chain overcomes sorafenib resistance in hepatocellular carcinoma.Sci. Rep.2019911725910.1038/s41598‑019‑53863‑2 31754201
    [Google Scholar]
  55. BistrovićA. KrstulovićL. HarejA. GrbčićP. SedićM. KoštrunS. PavelićS.K. BajićM. Raić-MalićS. Design, synthesis and biological evaluation of novel benzimidazole amidines as potent multi-target inhibitors for the treatment of non-small cell lung cancer.Eur. J. Med. Chem.20181431616163410.1016/j.ejmech.2017.10.061 29133046
    [Google Scholar]
  56. SharmaP. LaRosaC. AntwiJ. GovindarajanR. WerbovetzK.A. Imidazoles as potential anticancer agents: An update on recent studies.Molecules20212614421310.3390/molecules26144213 34299488
    [Google Scholar]
  57. KuangW.B. HuangR.Z. FangY.L. LiangG.B. YangC.H. MaX.L. ZhangY. Design, synthesis and pharmacological evaluation of novel 2-chloro-3-(1 H -benzo[ d]imidazol-2-yl)quinoline derivatives as antitumor agents: In vitro and in vivo antitumor activity, cell cycle arrest and apoptotic response.RSC Advances2018843243762438510.1039/C8RA04640A 35539175
    [Google Scholar]
  58. GuzmanJ. Natural cinnamic acids, synthetic derivatives and hybrids with antimicrobial activity.Molecules20141912192921934910.3390/molecules191219292 25429559
    [Google Scholar]
  59. DonthiboinaK. AnchiP. GurramS. SaiMani. G.; Lakshmi Uppu, J.; Godugu, C.; Shankaraiah, N.; Kamal, A. Synthesis and biological evaluation of substituted N-(2-(1H-benzo[d]imidazol-2-yl)phenyl)cinnamides as tubulin polymerization inhibitors.Bioorg. Chem.202010310419110.1016/j.bioorg.2020.104191 32891862
    [Google Scholar]
  60. LiA.L. YangY.Q. WangW.Y. LiuQ.S. SunY. GuW. Synthesis, cytotoxicity and apoptosis‐inducing activity of novel 1 H ‐benzo[ d]imidazole derivatives of dehydroabietic acid.J. Chin. Chem. Soc. (Taipei)20206791668167810.1002/jccs.202000075
    [Google Scholar]
  61. LiY. TanC. GaoC. ZhangC. LuanX. ChenX. LiuH. ChenY. JiangY. Discovery of benzimidazole derivatives as novel multi-target EGFR, VEGFR-2 and PDGFR kinase inhibitors.Bioorg. Med. Chem.201119154529453510.1016/j.bmc.2011.06.022 21724404
    [Google Scholar]
  62. LiL. QuanD. ChenJ. DingJ. ZhaoJ. LvL. ChenJ. Design, synthesis, and biological evaluation of 1-substituted -2-aryl imidazoles targeting tubulin polymerization as potential anticancer agents.Eur. J. Med. Chem.201918411173210.1016/j.ejmech.2019.111732 31610372
    [Google Scholar]
  63. BaiZ. LiuX. GuanQ. DingN. WeiQ. TongB. ZhaoM. ZhangW. MaL. 5-(3,4,5-trimethoxybenzoyl)-4-methyl-2-(p-tolyl) imidazol (BZML) targets tubulin and DNA to induce anticancer activity and overcome multidrug resistance in colorectal cancer cells.Chem. Biol. Interact.202031510888610.1016/j.cbi.2019.108886 31682804
    [Google Scholar]
  64. ZhaG.F. QinH.L. YoussifB.G.M. AmjadM.W. RajaM.A.G. AbdelazeemA.H. BukhariS.N.A. Discovery of potential anticancer multi-targeted ligustrazine based cyclohexanone and oxime analogs overcoming the cancer multidrug resistance.Eur. J. Med. Chem.2017135344810.1016/j.ejmech.2017.04.025 28431353
    [Google Scholar]
  65. FaragA.K. HassanA.H.E. AhnB.S. ParkK.D. RohE.J. Reprofiling of pyrimidine-based DAPK1/CSF1R dual inhibitors: identification of 2,5-diamino-4-pyrimidinol derivatives as novel potential anticancer lead compounds.J. Enzyme Inhib. Med. Chem.202035131132410.1080/14756366.2019.1699554 31809612
    [Google Scholar]
  66. NingC.Q. LuC. HuL. BiY.J. YaoL. HeY.J. LiuL.F. LiuX.Y. YuN.F. Macrocyclic compounds as anti-cancer agents: Design and synthesis of multi-acting inhibitors against HDAC, FLT3 and JAK2.Eur. J. Med. Chem.20159510411510.1016/j.ejmech.2015.03.034 25800646
    [Google Scholar]
  67. ShiZ.H. LiuF.T. TianH.Z. ZhangY.M. LiN.G. LuT. Design, synthesis and structure-activity relationship of diaryl-ureas with novel isoxazol[3,4-b]pyridine-3-amino-structure as multi-target inhibitors against receptor tyrosine kinase.Bioorg. Med. Chem.201826164735474410.1016/j.bmc.2018.08.013 30121211
    [Google Scholar]
  68. WangJ. ZhangL. PanX. DaiB. SunY. LiC. ZhangJ. Discovery of multi-target receptor tyrosine kinase inhibitors as novel anti-angiogenesis agents.Sci. Rep.2017714514510.1038/srep45145 28332573
    [Google Scholar]
  69. LiH. ZengY. ZiJ. HuY. MaG. WangX. ShanS. ChengG. XiongJ. Dietary flavonoids consumption and health: An umbrella review.Mol. Nutr. Food Res.20246812230072710.1002/mnfr.202300727 38813726
    [Google Scholar]
  70. KupfahlC. MichalkaA. Lass-FlörlC. FischerG. HaaseG. RuppertT. GeginatG. HofH. Gliotoxin production by clinical and environmental Aspergillus fumigatus strains.Int. J. Med. Microbiol.20082983-431932710.1016/j.ijmm.2007.04.006 17574915
    [Google Scholar]
  71. AmiriB. Yazdani TabriziM. NaziriM. MoradiF. ArzaghiM. ArchinI. BehaeinF. Bagheri PourA. GhannadikhoshP. ImanparvarS. Akhtari KohneshahriA. Sanaye AbbasiA. ZerangianN. AlijanzadehD. GhayyemH. AzizinezhadA. Ahmadpour YoushanluiM. PoudinehM. Neuroprotective effects of flavonoids: Endoplasmic reticulum as the target.Front. Neurosci.202418134815110.3389/fnins.2024.1348151 38957188
    [Google Scholar]
  72. NguyenV.T. LeeJ. QianZ.J. LiY.X. KimK.N. HeoS.J. JeonY.J. ParkW. ChoiI.W. JeJ.Y. JungW.K. Gliotoxin isolated from marine fungus Aspergillus sp. induces apoptosis of human cervical cancer and chondrosarcoma cells.Mar. Drugs2013121698710.3390/md12010069 24368570
    [Google Scholar]
  73. AbdelazeemA.H. El-SaadiM.T. SaidE.G. YoussifB.G.M. OmarH.A. El-MoghazyS.M. Novel diphenylthiazole derivatives with multi-target mechanism: Synthesis, docking study, anticancer and anti-inflammatory activities.Bioorg. Chem.20177512713810.1016/j.bioorg.2017.09.009 28938224
    [Google Scholar]
  74. StiborováM. PoljakováJ. MartínkováE. Bořek-DohalskáL. EckschlagerT. KizekR. FreiE. Ellipticine cytotoxicity to cancer cell lines—A comparative study.Interdiscip. Toxicol.201149810510.2478/v10102‑011‑0017‑7 21753906
    [Google Scholar]
  75. ZhuM. SunY. SuY. GuanW. WangY. HanJ. WangS. YangB. WangQ. KuangH. Luteolin: A promising multifunctional natural flavonoid for human diseases.Phytother. Res.20243873417344310.1002/ptr.8217 38666435
    [Google Scholar]
  76. AlyA.A. BräseS. HassanA.A. MohamedN.K. El-HaleemL.E.A. NiegerM. MorsyN.M. AlshammariM.B. IbrahimM.A.A. AbdelhafezE.M.N. Design, synthesis, and molecular docking of paracyclophanyl-thiazole hybrids as novel CDK1 inhibitors and apoptosis inducing anti-melanoma agents.Molecules20202523556910.3390/molecules25235569 33260954
    [Google Scholar]
  77. PardhasaradhiB.V.V. ReddyM. AliA.M. KumariA.L. KharA. Differential cytotoxic effects of Annona squamosa seed extracts on human tumour cell lines: Role of reactive oxygen species and glutathione.J. Biosci.200530223724410.1007/BF02703704 15886460
    [Google Scholar]
  78. MaC. WangQ. ShiY. LiY. WangX. LiX. ChenY. ChenJ. Three new antitumor annonaceous acetogenins from the seeds of Annona squamosa.Nat. Prod. Res.201731182085209010.1080/14786419.2016.1274897 28064519
    [Google Scholar]
  79. YounU.J. MiklossyG. ChaiX. WongwiwatthananukitS. ToyamaO. SongsakT. TurksonJ. ChangL.C. Bioactive sesquiterpene lactones and other compounds isolated from Vernonia cinerea.Fitoterapia20149319420010.1016/j.fitote.2013.12.013 24370662
    [Google Scholar]
  80. YounU.J. ParkE.J. KondratyukT.P. SimmonsC.J. BorrisR.P. TanamatayaratP. WongwiwatthananukitS. ToyamaO. SongsakT. PezzutoJ.M. ChangL.C. Anti-inflammatory sesquiterpene lactones from the flower of Vernonia cinerea.Bioorg. Med. Chem. Lett.201222175559556210.1016/j.bmcl.2012.07.010 22850207
    [Google Scholar]
  81. JungH.J. KimY. ShinJ.Y. SohngJ.K. KwonH.J. Antiangiogenic activity of herboxidiene via downregulation of vascular endothelial growth factor receptor-2 and hypoxia-inducible factor-1α.Arch. Pharm. Res.20153891728173510.1007/s12272‑015‑0625‑4 26195285
    [Google Scholar]
  82. BarrecaM.M. AlessandroR. CorradoC. Effects of flavonoids on cancer, cardiovascular and neurodegenerative diseases: Role of NF-κB signaling pathway.Int. J. Mol. Sci.20232411923610.3390/ijms24119236 37298188
    [Google Scholar]
  83. SarveswaranS. GautamS.C. GhoshJ. Wedelolactone, a medicinal plant-derived coumestan, induces caspase-dependent apoptosis in prostate cancer cells via downregulation of PKCε without inhibiting Akt.Int. J. Oncol.20124162191219910.3892/ijo.2012.1664 23076676
    [Google Scholar]
  84. ChoY.J. WooJ.H. LeeJ.S. JangD.S. LeeK.T. ChoiJ.H. Eclalbasaponin II induces autophagic and apoptotic cell death in human ovarian cancer cells.J. Pharmacol. Sci.2016132161410.1016/j.jphs.2016.02.006 27032907
    [Google Scholar]
  85. WangK. ChenX. Protective effect of flavonoids on oxidative stress injury in Alzheimer’s disease.Nat. Prod. Res.2024202412810.1080/14786419.2024.2345760 38910339
    [Google Scholar]
  86. HwangY.J. LeeE.J. KimH.R. HwangK.A. Molecular mechanisms of luteolin-7-O-glucoside-induced growth inhibition on human liver cancer cells: G2/M cell cycle arrest and caspase-independent apoptotic signaling pathways.BMB Rep.2013461261161610.5483/BMBRep.2013.46.12.133 24257119
    [Google Scholar]
  87. JiangD. RasulA. BatoolR. SarfrazI. HussainG. Mateen TahirM. QinT. SelamogluZ. AliM. LiJ. LiX. Potential anticancer properties and mechanisms of action of formononetin.BioMed Res. Int.2019201911110.1155/2019/5854315 31467899
    [Google Scholar]
  88. Don-DoncowN. EscobarZ. JohanssonM. KjellströmS. GarciaV. MunozE. SternerO. BjartellA. HellstenR. Galiellalactone is a direct inhibitor of the transcription factor STAT3 in prostate cancer cells.J. Biol. Chem.201428923159691597810.1074/jbc.M114.564252 24755219
    [Google Scholar]
  89. BuryM. GiraultA. MégalizziV. Spiegl-KreineckerS. MathieuV. BergerW. EvidenteA. KornienkoA. GaillyP. VandierC. KissR. Ophiobolin A induces paraptosis-like cell death in human glioblastoma cells by decreasing BKCa channel activity.Cell Death Dis.201343e56110.1038/cddis.2013.85 23538442
    [Google Scholar]
/content/journals/ctmc/10.2174/0115680266314693240914070250
Loading
/content/journals/ctmc/10.2174/0115680266314693240914070250
Loading

Data & Media loading...


  • Article Type:
    Review Article
Keyword(s): Alkaloids; Coumarins; Flavonoids; Heterocyclic rings; Phytochemicals; Terpenoids
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