Advanced search
Publication Cover
Journal of Enzyme Inhibition and Medicinal Chemistry Volume 37, 2022 - Issue 1
Submit an article Journal homepage
2,067
Views
6
CrossRef citations to date
0
Altmetric
Research Papers

Discovery of new 1H-pyrazolo[3,4-d]pyrimidine derivatives as anticancer agents targeting EGFRWT and EGFRT790M

Ahmed A. Gabera Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, EgyptView further author information
,
Mohamed Sobhya Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, EgyptView further author information
,
Abdallah Turkya Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, EgyptView further author information
,
Hanan Gaber Abdulwahabb Department of Pharmaceutical Medicinal Chemistry and Drug Design, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, EgyptView further author information
,
Ahmed A. Al-Karmalawyc Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta, EgyptORCID Iconhttps://orcid.org/0000-0002-8173-6073View further author information
ORCID Icon,
Mostafa. A. Elhendawyd Department of Chemistry and Biochemistry, University of Mississippi, MS, USA;e Department of Agriculture Chemistry, Faculty of Agriculture, Damietta University, Damietta, EgyptView further author information
,
Mohamed. M. Radwanf National Center for Natural Products Research, University of Mississippi, University, MS, USA;g Department of Pharmacognosy, Faculty of Pharmacy, Alexandria University, Alexandria, EgyptView further author information
,
Eslam B. Elkaeedh Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Riyadh, Saudi ArabiaView further author information
,
Ibrahim M. Ibrahimi Biophysics Department, Faculty of Science, Cairo University, Cairo, EgyptView further author information
,
Heba S. A. Elzahabib Department of Pharmaceutical Medicinal Chemistry and Drug Design, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, EgyptView further author information
&
Ibrahim H. Eissaj Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, EgyptCorrespondence[email protected]
ORCID Iconhttps://orcid.org/0000-0002-6955-2263View further author information
ORCID Icon show all
Pages 2283-2303 | Received 18 May 2022, Accepted 06 Aug 2022, Published online: 23 Aug 2022

References

  • Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA 2021;71:209–49.
  • Siegel RL, Miller KD, Fuchs HE, Jemal A. Ahmedin Jemal, Cancer statistics, 2022. CA 2022;72:7–33.
  • Ogunbiyi JO, Stefan DC, Rebbeck TR. African Organization for Research and Training in Cancer: position and vision for cancer research on the African Continent. Infect Agents Cancer 2016;11:1–6.
  • Michor F, Iwasa Y, Nowak MA. Dynamics of cancer progression. Nat Rev Cancer 2004;4:197–205.
  • Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nature Medicine 2013;19:1423–37.
  • Eastern Cooperative Oncology Group, Schiller D, Harrington CP, Belani C, et al. Comparison of four chemotherapy regimens for advanced non–small-cell lung cancer. N Engl J Med 2002;346:92–8.
  • Mongre RK, Mishra CB, Shukla AK, et al. Emerging importance of tyrosine kinase inhibitors against cancer: quo vadis to cure? Int J Molecul Sc 2021;22:11659.
  • Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell 2000;103:211–25.
  • Metibemu DS, Akinloye OA, Akamo AJ, et al. Exploring receptor tyrosine kinases-inhibitors in Cancer treatments. Egyptian J Med Human Genet 2019;20:1–16.
  • Yamaoka T, Kusumoto S, Ando K, et al. Receptor tyrosine kinase-targeted cancer therapy. Int J Molecul Sci 2018;19:3491.
  • Butti R, Das S, Gunasekaran VP, et al. Receptor tyrosine kinases (RTKs) in breast cancer: signaling, therapeutic implications and challenges. Molecular Cancer 2018;17:1–18.
  • Olayioye MA, Neve RM, Lane HA, Hynes NE. The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J 2000;19:3159–67.
  • de Castro Barbosa ML, Lima LM, Tesch R, et al. Novel 2-chloro-4-anilino-quinazoline derivatives as EGFR and VEGFR-2 dual inhibitors. Eur J Med Chem 2014;71:1–14.
  • Chang J, Ren H, Zhao M, et al. Development of a series of novel 4-anlinoquinazoline derivatives possessing quinazoline skeleton: design, synthesis, EGFR kinase inhibitory efficacy, and evaluation of anticancer activities in vitro. Eur J Med Chem 2017;138:669–88.
  • Chen Y, Wu J, Wang A, et al. Discovery of N-(5-((5-chloro-4-((2-(isopropylsulfonyl) phenyl) amino) pyrimidin-2-yl) amino)-4-methoxy-2-(4-methyl-1, 4-diazepan-1-yl) phenyl) acrylamide (CHMFL-ALK/EGFR-050) as a potent ALK/EGFR dual kinase inhibitor capable of overcoming a variety of ALK/EGFR associated drug resistant mutants in NSCLC. Eur J Med Chem 2017;139:674–97.
  • Nicholson RI, Gee JM, Harper ME. EGFR and cancer prognosis. Eur J Cancer 2001;37:9–15.
  • Zhang H-Q, Gong F-H, Ye J-Q, et al. Design and discovery of 4-anilinoquinazoline-urea derivatives as dual TK inhibitors of EGFR and VEGFR-2. Eur J Med Chem 2017;125:245–54.
  • Song Z, Huang S, Yu H, et al. Synthesis and biological evaluation of morpholine-substituted diphenylpyrimidine derivatives (Mor-DPPYs) as potent EGFR T790M inhibitors with improved activity toward the gefitinib-resistant non-small cell lung cancers (NSCLC). Eur J Med Chem 2017;133:329–39.
  • Zhang Y, Chen L, Xu H, et al. 6, 7-Dimorpholinoalkoxy quinazoline derivatives as potent EGFR inhibitors with enhanced antiproliferative activities against tumor cells. Eur J Med Chem 2018;147:77–89.
  • Abdelsalam EA, Zaghary WA, Amin KM, et al. Synthesis and in vitro anticancer evaluation of some fused indazoles, quinazolines and quinolines as potential EGFR inhibitors. Bioorganic Chemistry 2019;89:102985.
  • Ismail RS, Abou-Seri SM, Eldehna WM, et al. Novel series of 6-(2-substitutedacetamido)-4-anilinoquinazolines as EGFR-ERK signal transduction inhibitors in MCF-7 breast cancer cells. Eur J Med Chem 2018;155:782–96.
  • Bonomi P. Erlotinib: a new therapeutic approach for non-small cell lung cancer. Expert Opin Investigat Drugs 2003;12:1395–401.
  • Celik T, Kosker M. Ocular side effects and trichomegaly of eyelashes induced by erlotinib: a case report and review of the literature. Contact Lens Anterior Eye 2015;38:59–60.
  • Muhsin M, Graham J, Kirkpatrick P. Gefitinib. Berlin, Germany: Nature Publishing Group; 2003.
  • Pao W, Miller VA, Politi KA, et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2005;2:e73.
  • U.S. Food & Drug Administration. FDA approves neratinib for extended adjuvant treatment of early stage HER2-positive breast cancer. 2017.
  • Sequist LV, Besse B, Lynch TJ, et al. Neratinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor: results of a phase II trial in patients with advanced non–small-cell lung cancer. J Clin Oncol 2010;28:3076–83.
  • Kim Y, Ko J, Cui Z, et al. The EGFR T790M mutation in acquired resistance to an irreversible second-generation EGFR inhibitor. Mol Cancer Ther 2012;11:784–91.
  • Jänne PA, Yang JC-H, Kim D-W, et al. AZD9291 in EGFR inhibitor–resistant non–small-cell lung cancer. N Engl J Med 2015;372:1689–99.
  • Carroll J. Following lethal tox report, Boehringer scraps plans for high-speed development, kills $730M Hanmi deal. 2019. https://endpts.com/following-lethal-tox-report-boehringer-scraps-plans-for-high-speed-development-kills-730m-hanmi-deal/
  • Zhao Z, Wu H, Wang L, et al. Exploration of type II binding mode: a privileged approach for kinase inhibitor focused drug discovery? ACS Chem Biol 2014;9:1230–41.
  • Mowafy S, Galanis A, Doctor ZM, et al. Toward discovery of mutant EGFR inhibitors; Design, synthesis and in vitro biological evaluation of potent 4-arylamino-6-ureido and thioureido-quinazoline derivatives. Biorg. Med. Chem 2016;24:3501–12.
  • Furet P, Caravatti G, Lydon N, et al. Modelling study of protein kinase inhibitors: binding mode of staurosporine and origin of the selectivity of CGP 52411. J. Comput. Aided Mol. Des 1995;9:465–72.
  • Gandin V, Ferrarese A, Dalla Via M, et al. Targeting kinases with anilinopyrimidines: discovery of N-phenyl-N’-[4-(pyrimidin-4-ylamino) phenyl] urea derivatives as selective inhibitors of class III receptor tyrosine kinase subfamily. Scientific Reports 2015;5:16750.
  • Liu Y, Gray NS. Rational design of inhibitors that bind to inactive kinase conformations. Nature Chem Biol 2006;2:358–64.
  • Ismail NS, Ali EM, Ibrahim DA, et al. Pyrazolo [3, 4-d] pyrimidine based scaffold derivatives targeting kinases as anticancer agents. Future J Pharmaceut Sci 2016;2:20–30.
  • Traxler P, Bold G, Frei J, et al. Use of a pharmacophore model for the design of EGF-R tyrosine kinase inhibitors: 4-(phenylamino) pyrazolo [3, 4-d] pyrimidines. J. Med. Chem 1997;40:3601–16.
  • Gaber AA, Bayoumi AH, El-Morsy AM, et al. Design, synthesis and anticancer evaluation of 1H-pyrazolo [3, 4-d] pyrimidine derivatives as potent EGFRWT and EGFRT790M inhibitors and apoptosis inducers. Bioorg Chem 2018;80:375–95.
  • Abbas SES, Aly EI, Awadallah FM, Mahmoud WR. 4‐Substituted‐1‐phenyl‐1H‐pyrazolo [3, 4‐d] pyrimidine derivatives: design, synthesis, antitumor and EGFR tyrosine kinase inhibitory activity. Chem Biol Drug Design 2015;85:608–22.
  • Abbas SES, Aly EI, Awadallah FM, Mahmoud WR. Design, 4‐substituted‐1‐phenyl‐1H‐pyrazolo [3, 4‐d] pyrimidine derivatives: design. Synthesis, Antitumor EGFR Tyrosine Kinase Inhibitory Activity. Chem Biol Drug Des 2015;85:608–22.
  • Li R, Tang H, Fu H, et al. Arynes double bond insertion/nucleophilic addition with vinylogous amides and carbodiimides. J Org Chem 2014;79:1344–55.
  • Sharma VK, Nandekar PP, Sangamwar A, et al. Structure guided design and binding analysis of EGFR inhibiting analogues of erlotinib and AEE788 using ensemble docking, molecular dynamics and MM-GBSA. RSC Adv 2016;6:65725–35.
  • Traxler P, Furet P. Strategies toward the design of novel and selective protein tyrosine kinase inhibitors. Pharmacol Ther 1999;82:195–206.
  • Schenone S, Radi M, Musumeci F, et al. Biologically driven synthesis of pyrazolo [3, 4-d] pyrimidines as protein kinase inhibitors: an old scaffold as a new tool for medicinal chemistry and chemical biology studies. Chem. Rev 2014;114:7189–238.
  • He H-Y, Zhao J-N, Jia R, et al. Novel pyrazolo [3, 4-d] pyrimidine derivatives as potential antitumor agents: exploratory synthesis, preliminary structure-activity relationships, and in vitro biological evaluation. Molecules 2011;16:10685–94.
  • Cheng C, ROBINS RK. Potential Purine Antagonists. XII. Synthesis of 1-Alkyl (aryl)-4, 6-disubstituted Pyrazolo [3, 4-d] pyrimidines1. J Org Chem 1958;23:852–61.
  • Ibrahim M, Taghour M, Metwaly A, et al. Design, synthesis, molecular modeling and anti-proliferative evaluation of novel quinoxaline derivatives as potential DNA intercalators and topoisomerase II inhibitors. Eur J Med Chem 2018;155:117–34.
  • Yang J, Qu X, Russell P, Goldstein D. Regulation of epidermal growth factor receptor in human colon cancer cell lines by interferon α. Gut 2004;53:123–9.
  • Qian Y, Qiu M, Wu Q, et al. Enhanced cytotoxic activity of cetuximab in EGFR-positive lung cancer by conjugating with gold nanoparticles. Scientific Reports 2014;4:7490–8.
  • Park JH, Liu Y, Lemmon MA, Radhakrishnan R. Erlotinib binds both inactive and active conformations of the EGFR tyrosine kinase domain. Biochem J 2012;448:417–23.
  • Sogabe S, Kawakita Y, Igaki S, et al. Structure-based approach for the discovery of pyrrolo [3, 2-d] pyrimidine-based EGFR T790M/L858R mutant inhibitors. ACS Med Chem Lett 2013;4:201–5.
  • Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983;65:55–63.
  • Denizot F, Lang R. Rapid colorimetric assay for cell growth and survival: modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods 1986;89:271–7.
  • Thabrew MI, Hughes RD, McFarlane IG. Screening of hepatoprotective plant components using a HepG2 cell cytotoxicity assay. J Pharm Pharmacol 2011;49:1132–5.
  • Al-Rashood ST, Hamed AR, Hassan GS, et al. Antitumor properties of certain spirooxindoles towards hepatocellular carcinoma endowed with antioxidant activity. J Enzyme Inhibit Med Chem 2020;35:831–9.
  • Eldehna WM, Hassan GS, Al-Rashood ST, et al. Synthesis and in vitro anticancer activity of certain novel 1-(2-methyl-6-arylpyridin-3-yl)-3-phenylureas as apoptosis-inducing agents. J Enzyme Inhib Med Chem 2019;34:322–32.
  • Sabt A, Abdelhafez OM, El-Haggar RS, et al. Novel coumarin-6-sulfonamides as apoptotic anti-proliferative agents: synthesis, in vitro biological evaluation, and QSAR studies. J Enzyme Inhib Med Chem 2018;33:1095–107.
  • Wang J, Lenardo MJ. Roles of caspases in apoptosis, development, and cytokine maturation revealed by homozygous gene deficiencies. J Cell Sci 2000;113:753–7.
  • Al-Sanea MM, Al-Ansary GH, Elsayed ZM, et al. Development of 3-methyl/3-(morpholinomethyl) benzofuran derivatives as novel antitumor agents towards non-small cell lung cancer cells. J Enzyme Inhib Med Chem 2021;36:987–99.
  • Balah A, Ezzat O, Akool E-S. Vitamin E inhibits cyclosporin A-induced CTGF and TIMP-1 expression by repressing ROS-mediated activation of TGF-β/Smad signaling pathway in rat liver. Int Immunopharmacol 2018;65:493–502.
  • Aborehab NM, Elnagar MR, Waly NE. Gallic acid potentiates the apoptotic effect of paclitaxel and carboplatin via overexpression of Bax and P53 on the MCF‐7 human breast cancer cell line. J Biochem Mol Toxicol 2021;35:e22638.
  • Elnagar MR, Walls AB, Helal GK, et al. Functional characterization of α7 nicotinic acetylcholine and NMDA receptor signaling in SH-SY5Y neuroblastoma cells in an ERK phosphorylation assay. Eur J Pharmacol 2018;826:106–13.
  • El-Adl K, Ibrahim M-K, Alesawy MS, Eissa IH. [1, 2, 4] Triazolo [4, 3-c] quinazoline and bis ([1, 2, 4] triazolo)[4, 3-a: 4′, 3′-c] quinazoline derived DNA intercalators: design, synthesis, in silico ADMET profile, molecular docking and anti-proliferative evaluation studies. Bioorg Med Chem 2021;30:115958.
  • Alanazi MM, Mahdy HA, Alsaif NA, et al. New bis ([1, 2, 4] triazolo)[4, 3-a: 3′, 4′-c] quinoxaline derivatives as VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, in silico studies, and anticancer evaluation. Bioorg Chem 2021;112:104949.
  • El-Metwally SA, Abou-El-Regal MM, Eissa IH, et al. Discovery of thieno [2, 3-d] pyrimidine-based derivatives as potent VEGFR-2 kinase inhibitors and anti-cancer agents. Bioorg Chem 2021;112:104947.
  • Parmar DR, Soni JY, Guduru R, et al. Discovery of new anticancer thiourea-azetidine hybrids: design, synthesis, in vitro antiproliferative, SAR, in silico molecular docking against VEGFR-2, ADMET, toxicity, and DFT studies. Bioorg Chem 2021;115:105206.
  • Suleimen YM, Jose RA, Suleimen RN, et al. Isolation and in silico anti-SARS-CoV-2 papain-like protease potentialities of two rare 2-phenoxychromone derivatives from Artemisia spp. Molecules 2022;27:1216.
  • Jo S, Kim T, Iyer VG, Im W. CHARMM-GUI: a web-based graphical user interface for CHARMM. J Computat Chem 2008;29:1859–65.
  • Brooks BR, Brooks CL, III, Mackerell AD, Jr, et al. CHARMM: the biomolecular simulation program. J Computat Chem 2009;30:1545–614.
  • Lee J, Cheng X, Swails JM, et al. CHARMM-GUI input generator for NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM simulations using the CHARMM36 additive force field. J Chem Theory Comput 2016;12:405–13.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.