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Research Papers

New benzoxazole derivatives as potential VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, anti-proliferative evaluation, flowcytometric analysis, and in silico studies

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Pages 403-416 | Received 19 Oct 2021, Accepted 01 Dec 2021, Published online: 27 Dec 2021

References

  • Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1995;1:27–30.
  • Kerbel RS. Tumor angiogenesis: past, present and the near future. Carcinogenesis 2000;21:505–15.
  • Behdani M, Zeinali S, Khanahmad H, et al. Generation and characterization of a functional nanobody against the vascular endothelial growth factor receptor-2; angiogenesis cell receptor. Mol Immunol 2012;50:35–41.
  • Lee YT, Tan YJ, Oon CE. Molecular targeted therapy: treating cancer with specificity. Eur J Pharmacol 2018;834:188–96.
  • Chen H, Kovar J, Sissons S, et al. A cell-based immunocytochemical assay for monitoring kinase signaling pathways and drug efficacy. Anal Biochem 2005;338:136–42.
  • Traxler P, Furet P. Strategies toward the design of novel and selective protein tyrosine kinase inhibitors. Pharmacol Ther 1999;82:195–206.
  • Cui JJ, Tran-Dubé M, Shen H, et al. Structure based drug design of crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK). J Med Chem 2011;54:6342–63.
  • Veeravagu A, Hsu AR, Cai W, et al. Vascular endothelial growth factor and vascular endothelial growth factor receptor inhibitors as anti-angiogenic agents in cancer therapy. Recent Pat Anticancer Drug Discov. 2007;2:59–71.
  • El-Adl K, El-Helby A-GA, Ayyad RR, et al. Design, synthesis, and anti-proliferative evaluation of new quinazolin-4(3H)-ones as potential VEGFR-2 inhibitors. Bioorg Med Chem 2021;29:115872.
  • Eissa IH, El-Helby A-GA, Mahdy HA, et al. Discovery of new quinazolin-4(3H)-ones as VEGFR-2 inhibitors: design, synthesis, and anti-proliferative evaluation. Bioorg Chem 2020;105:104380.
  • Kang D, Pang X, Lian W, et al. Discovery of VEGFR2 inhibitors by integrating naïve Bayesian classification, molecular docking and drug screening approaches. RSC Adv 2018;8:5286–97.
  • El‐Helby AGA, Sakr H, Eissa IH, et al. Benzoxazole/benzothiazole‐derived VEGFR‐2 inhibitors: design, synthesis, molecular docking, and anticancer evaluations. Archiv Pharma 2019;352:1900178.
  • Claesson‐Welsh L, Welsh M. VEGFA and tumour angiogenesis. J Intern Med 2013;273:114–27.
  • 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-Helby A-GA, Sakr H, Ayyad RR, et al. Design, synthesis, molecular modeling, in vivo studies and anticancer activity evaluation of new phthalazine derivatives as potential DNA intercalators and topoisomerase II inhibitors. Bioorg Chem 2020;103:104233.
  • Abbass EM, Khalil AK, Mohamed MM, et al. Design, efficient synthesis, docking studies, and anticancer evaluation of new quinoxalines as potential intercalative Topo II inhibitors and apoptosis inducers. Bioorg Chem 2020;104:104255.
  • Eissa IH, Ibrahim MK, Metwaly AM, et al. Design, molecular docking, in vitro, and in vivo studies of new quinazolin-4(3H)-ones as VEGFR-2 inhibitors with potential activity against hepatocellular carcinoma. Bioorg Chem 2021;107:104532.
  • 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.
  • Eissa IH, Dahab MA, Ibrahim MK, et al. Design and discovery of new antiproliferative 1,2,4-triazin-3(2H)-ones as tubulin polymerization inhibitors targeting colchicine binding site. Bioorg Chem 2021;112:104965.
  • Saleh NM, Abdel‐Rahman AAH, Omar AM, et al. Pyridine‐derived VEGFR‐2 inhibitors: rational design, synthesis, anticancer evaluations, in silico ADMET profile, and molecular docking. Archiv Pharma 2021;354:e2100085.
  • Ran F, Li W, Qin Y, et al. Inhibition of vascular smooth muscle and cancer cell proliferation by new VEGFR inhibitors and their immunomodulator effect: design, synthesis, and biological evaluation. Oxid Med Cell Longev 2021;2021:1–21.
  • Alsaif NA, Dahab MA, Alanazi MM, et al. New quinoxaline derivatives as VEGFR-2 inhibitors with anticancer and apoptotic activity: design, molecular modeling, and synthesis. Bioorg Chem 2021;110:104807.
  • El-Adl K, Sakr HM, Yousef RG, et al. Discovery of new quinoxaline-2(1H)-one-based anticancer agents targeting VEGFR-2 as inhibitors: design, synthesis, and anti-proliferative evaluation. Bioorg Chem 2021;114:105105.
  • Alsaif NA, Taghour MS, Alanazi MM, et al. Discovery of new VEGFR-2 inhibitors based on bis([1,2,4]triazolo)[4,3-a:3′,4′-c]quinoxaline derivatives as anticancer agents and apoptosis inducers. J Enzyme Inhib Med Chem 2021;36:1093–114.
  • Mahdy HA, Ibrahim MK, Metwaly AM, et al. Design, synthesis, molecular modeling, in vivo studies and anticancer evaluation of quinazolin-4(3H)-one derivatives as potential VEGFR-2 inhibitors and apoptosis inducers. Bioorg Chem 2020;94:103422.
  • 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.
  • Hagras M, El Deeb MA, Elzahabi HS, et al. Discovery of new quinolines as potent colchicine binding site inhibitors: design, synthesis, docking studies, and anti-proliferative evaluation. J Enzyme Inhib Med Chem 2021;36:640–58.
  • El‐Adl K, Ibrahim MK, Khedr F, et al. N‐substituted‐4‐phenylphthalazin‐1‐amine‐derived VEGFR‐2 inhibitors: design, synthesis, molecular docking, and anticancer evaluation studies. Archiv Pharma 2021;354:2000219.
  • El-Adl K, El-Helby A-GA, Sakr H, et al. Design, synthesis, molecular docking and anticancer evaluations of 5-benzylidenethiazolidine-2,4-dione derivatives targeting VEGFR-2 enzyme. Bioorg Chem 2020;102:104059.
  • Lee K, Jeong K-W, Lee Y, et al. Pharmacophore modeling and virtual screening studies for new VEGFR-2 kinase inhibitors. Eur J Med Chem 2010;45:5420–7.
  • Machado VA, Peixoto D, Costa R, et al. Synthesis, antiangiogenesis evaluation and molecular docking studies of 1-aryl-3-[(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas: discovery of a new substitution pattern for type II VEGFR-2 Tyr kinase inhibitors. Bioorg Med Chem 2015;23:6497–509.
  • Garofalo A, Goossens L, Six P, et al. Impact of aryloxy-linked quinazolines: a novel series of selective VEGFR-2 receptor tyrosine kinase inhibitors. Bioorg Med Chem Lett 2011;21:2106–12.
  • Kaul S, Kumar A, Sain B, Bhatnagar AK. Simple and convenient one‐pot synthesis of benzimidazoles and benzoxazoles using N,N‐Dimethylchlorosulfitemethaniminium chloride as condensing agent. Synth Commun 2007;37:2457–60.
  • Ibrahim M-K, El-Adl K, Zayed MF, Mahdy HA. Design, synthesis, docking, and biological evaluation of some novel 5-chloro-2-substituted sulfanylbenzoxazole derivatives as anticonvulsant agents. Med Chem Res 2015;24:99–114.
  • Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983;65:55–63.
  • 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.
  • Lo KK-W, Lee TK-M, Lau JS-Y, et al. Luminescent biological probes derived from ruthenium(II) estradiol polypyridine complexes. Inorg Chem 2008;47:200–8.
  • El‐Helby AGA, Ayyad RR, Zayed MF, et al. Design, synthesis, in silico ADMET profile and GABA‐A docking of novel phthalazines as potent anticonvulsants. Archiv Pharma 2019;352:1800387.
  • El-Helby A-GA, Ayyad RR, El-Adl K, Elkady H. Phthalazine-1,4-dione derivatives as non-competitive AMPA receptor antagonists: design, synthesis, anticonvulsant evaluation, ADMET profile and molecular docking. Mol Divers 2019;23:283–98.
  • Abdallah AE, Alesawy MS, Eissa SI, et al. Design and synthesis of new 4-(2- nitrophenoxy)benzamide derivatives as potential antiviral agents: molecular modeling and in vitro antiviral screening. New J Chem 2021;45(36):16557–16571.
  • Al-Rashood ST, Hamed AR, Hassan GS, et al. Antitumor properties of certain spirooxindoles towards hepatocellular carcinoma endowed with antioxidant activity. J Enzyme Inhib Med Chem 2020;35:831–9.
  • Ismail A, Doghish AS, Elsadek BEM, et al. Hydroxycitric acid potentiates the cytotoxic effect of tamoxifen in MCF-7 breast cancer cells through inhibition of ATP citrate lyase. Steroids 2020;160:108656.
  • El-Mahdy HA, El-Husseiny AA, Kandil YI, El-Din AMG. Diltiazem potentiates the cytotoxicity of gemcitabine and 5-fluorouracil in PANC-1 human pancreatic cancer cells through inhibition of P-glycoprotein. Life Sci 2020;262:118518.
  • El-Zahabi MA, Sakr H, El-Adl K, et al. Design, synthesis, and biological evaluation of new challenging thalidomide analogs as potential anticancer immunomodulatory agents. Bioorg Chem 2020;104:104218.
  • Sharma K, Suresh P, Mullangi R, Srinivas N. Quantitation of VEGFR2 (vascular endothelial growth factor receptor) inhibitors-review of assay methodologies and perspectives. Biomed Chromatogr 2015;29:803–34.
  • Lin J-Y, Lo K-Y, Sun Y-S. Effects of substrate-coating materials on the wound-healing process. Materials 2019;12:2775.
  • Kassab AE, Gedawy EM, Hamed MI, et al. Design, synthesis, anticancer evaluation, and molecular modelling studies of novel tolmetin derivatives as potential VEGFR-2 inhibitors and apoptosis inducers. J Enzyme Inhib Med Chem 2021;36:922–39.
  • Nasser AA, Eissa IH, Oun MR, et al. Discovery of new pyrimidine-5-carbonitrile derivatives as anticancer agents targeting EGFRWT and EGFRT790M. Org Biomol Chem 2020;18:7608–34.
  • Ibrahim MK, Eissa IH, Abdallah AE, et al. Design, synthesis, molecular modeling and anti-hyperglycemic evaluation of novel quinoxaline derivatives as potential PPARγ and SUR agonists. Bioorg Med Chem 2017;25:1496–513.
  • El-Helby AGA, Ayyad RR, Sakr HM, et al. Design, synthesis, molecular modeling and biological evaluation of novel 2,3-dihydrophthalazine-1,4-dione derivatives as potential anticonvulsant agents. J Mol Struct 2017;1130:333–51.
  • Ibrahim MK, Eissa IH, Alesawy MS, et al. Design, synthesis, molecular modeling and anti-hyperglycemic evaluation of quinazolin-4(3H)-one derivatives as potential PPARγ and SUR agonists. Bioorg Med Chem 2017;25:4723–44.
  • El-Gamal KM, El-Morsy AM, Saad AM, et al. Synthesis, docking, QSAR, ADMET and antimicrobial evaluation of new quinoline-3-carbonitrile derivatives as potential DNA-gyrase inhibitors. J Mol Struct 2018;1166:15–33.
  • El-Zahabi MA, Elbendary ER, Bamanie FH, et al. Design, synthesis, molecular modeling and anti-hyperglycemic evaluation of phthalimide-sulfonylurea hybrids as PPARγ and SUR agonists. Bioorg Chem 2019;91:103115.
  • Alanazi MM, Eissa IH, Alsaif NA, et al. Design, synthesis, docking, ADMET studies, and anticancer evaluation of new 3-methylquinoxaline derivatives as VEGFR-2 inhibitors and apoptosis inducers. J Enzyme Inhib Med Chem 2021;36:1760–82.