2,295
Views
5
CrossRef citations to date
0
Altmetric
Research Papers

New quinoline and isatin derivatives as apoptotic VEGFR-2 inhibitors: design, synthesis, anti-proliferative activity, docking, ADMET, toxicity, and MD simulation studies

, , ORCID Icon, , , , , , , ORCID Icon & show all
Pages 2191-2205 | Received 16 Jun 2022, Accepted 02 Aug 2022, Published online: 16 Aug 2022

References

  • WHO Cancer. Key facts. https://www.who.int/news-room/fact-sheets/detail/cancer [last accessed 26 Jan 2022].
  • NHS Cancer. Overview. https://www.nhs.uk/conditions/cancer/ [last accessed 27 Jan 2022].
  • Wong MC, Huang J, Lok V, et al. Differences in incidence and mortality trends of colorectal cancer worldwide based on sex, age, and anatomic location. Clin Gastroenterol Hepatol 2021;19:955–66. e61.
  • Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394–424.
  • Meier P, Finch A, Evan G. Apoptosis in development. Nature 2000;407:796–801.
  • Lowe SW, Lin AW. Apoptosis in cancer. Carcinogenesis 2000;21:485–95.
  • Fernald K, Kurokawa M. Evading apoptosis in cancer. Trends Cell Biol 2013;23:620–33.
  • Farghaly TA, Al-Hasani WA, Abdulwahab HG. An updated patent review of VEGFR-2 inhibitors (2017-present). Exp Opin Ther Pat 2021;31:989–1007. (just-accepted).
  • Li Y, Zhang F, Nagai N, et al. VEGF-B inhibits apoptosis via VEGFR-1–mediated suppression of the expression of BH3-only protein genes in mice and rats. J Clin Invest 2008;118:913–23.
  • Xiao X, Wu J, Zhu X, et al. Induction of cell cycle arrest and apoptosis in human nasopharyngeal carcinoma cells by ZD6474, an inhibitor of VEGFR tyrosine kinase with additional activity against EGFR tyrosine kinase. Int J Cancer 2007;121:2095–104.
  • Otrock ZK, Mahfouz RA, Makarem JA, Shamseddine AI. Understanding the biology of angiogenesis: review of the most important molecular mechanisms. Blood Cells Mol Dis 2007;39:212–20.
  • Ferrara N, Gerber H-P, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003;9:669–76.
  • Dvorak HF. Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol 2002;20:4368–80.
  • Cross MJ, Dixelius J, Matsumoto T, Claesson-Welsh L. VEGF-receptor signal transduction. Trends Biochem Sci 2003;28:488–94.
  • Marrone TJ, Briggs a, James M, McCammon JA. Structure-based drug design: computational advances. Annu Rev Pharmacol Toxicol 1997;37:71–90.
  • Li N, Wang Y, Li W, et al. Screening of some sulfonamide and sulfonylurea derivatives as anti-Alzheimer’s agents targeting BACE1 and PPARγ. J Chem 2020;2020:1–19.
  • Abdel-Aziz HA, Eldehna WM, Fares M, et al. Synthesis, biological evaluation and 2D-QSAR study of halophenyl bis-hydrazones as antimicrobial and antitubercular agents. Int J Mol Sci 2015;16:8719–43.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Dietrich J, Hulme C, Hurley LH. The design, synthesis, and evaluation of 8 hybrid DFG-out allosteric kinase inhibitors: a structural analysis of the binding interactions of Gleevec®, Nexavar®, and BIRB-796. Bioorg Med Chem 2010;18:5738–48.
  • Viegas-Junior C, Danuello A, da Silva Bolzani V, et al. Molecular hybridization: a useful tool in the design of new drug prototypes. Curr Med Chem 2007;14:1829–52.
  • Meth-Cohn O, Narine B, Tarnowski B. A versatile new synthesis of quinolines and related fused pyridines, Part 5. The synthesis of 2-chloroquinoline-3-carbaldehydes. J Chem Soc Perkin Trans 1 1981;1520–30.
  • Kar K, Krithika U, Basu P, et al. Design, synthesis and glucose uptake activity of some novel glitazones. Bioorg Chem 2014;56:27–33.
  • Shih M-H, Yeh M-Y. Access to the syntheses of sydnonyl-substituted α, β-unsaturated ketones and 1, 3-dihydro-indol-2-ones by modified Knoevenagel reaction. Tetrahedron 2003;59:4103–11.
  • 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 M, Hughes RD, Mcfarlane IG. Screening of hepatoprotective plant components using a HepG2 cell cytotoxicity assay. J Pharm Pharmacol 2011;49:1132–5.
  • Pritchett JC, Naesens L, Montoya J. Treating HHV-6 infections: the laboratory efficacy and clinical use of anti-HHV-6 agents. In: Flamand L, Lautenschlager I, Krueger G, Ablashi D, ed. Human herpesviruses HHV-6A, HHV-6B & HHV-7. 3rd ed. Amsterdam, Netherlands: Elsevier; 2014.
  • Peña-Morán OA, Villarreal ML, Álvarez-Berber L, et al. Cytotoxicity, post-treatment recovery, and selectivity analysis of naturally occurring podophyllotoxins from Bursera fagaroides var. fagaroides on breast cancer cell lines. Molecules. 2016;21:1013.
  • Indrayanto G, Putra GS, Suhud F. Excipients, R. Methodology, Validation of in-vitro bioassay methods: application in herbal drug research. Profiles Drug Subst Excip Relat Methodol. 2021;46:273–307.
  • Liang C-C, Park AY, Guan J-L. In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protocols 2007;2:329–33.
  • Kim R. Unknotting the roles of Bcl-2 and Bcl-xL in cell death. Biochem Biophys Res Commun 2005;333:336–43.
  • Yang J, Song K, Krebs TL, et al. Rb/E2F4 and Smad2/3 link survivin to TGF-β-induced apoptosis and tumor progression. Oncogene 2008;27:5326–38.
  • Liu Y, Gray NS. Rational design of inhibitors that bind to inactive kinase conformations. Nat Chem Biol 2006;2:358–64.
  • Sousa SF, Fernandes PA, Ramos MJ. Protein–ligand docking: current status and future challenges. Proteins 2006;65:15–26.
  • Hollingsworth SA, Dror RO. Molecular dynamics simulation for all. Neuron 2018;99:1129–43.
  • Hansson T, Oostenbrink C, van Gunsteren W. Molecular dynamics simulations. Current Opin Struct Biol 2002;12:190–6.
  • Durrant JD, McCammon JA. Molecular dynamics simulations and drug discovery. BMC Biol 2011;9:71–9.
  • Kuzmanic A, Zagrovic B. Determination of ensemble-average pairwise root mean-square deviation from experimental B-factors. Biophys J 2010;98:861–71.
  • Liu P, Lu J, Yu H, et al. Lubricant shear thinning behavior correlated with variation of radius of gyration via molecular dynamics simulations. J Chem Phys 2017;147:084904.
  • Kumar K, Anbarasu A, Ramaiah S. Molecular docking and molecular dynamics studies on β-lactamases and penicillin binding proteins. Mol BioSyst 2014;10:891–900.
  • El-Deeb NM, Ibrahim OM, Mohamed MA, et al. Alginate/κ-carrageenan oral microcapsules loaded with Agaricus bisporus polysaccharides MH751906 for natural killer cells mediated colon cancer immunotherapy. Int J Biol Macromol 2022;205:385–95.
  • Abou-Seri SM, Eldehna WM, Ali MM, Abou El Ella DA. 1-Piperazinylphthalazines as potential VEGFR-2 inhibitors and anticancer agents: synthesis and in vitro biological evaluation. Eur J Med Chem 2016;107:165–79.
  • Borenfreund E, Puerner JA. Toxicity determined in vitro by morphological alterations and neutral red absorption. Toxicol Lett 1985;24:119–24.
  • Koch A, Tamez P, Pezzuto J, Soejarto D. Evaluation of plants used for antimalarial treatment by the Maasai of Kenya. J Ethnopharmacol 2005;101:95–9.
  • Arranz-Valsero I, Soriano-Romaní L, García-Posadas L, et al. IL-6 as a corneal wound healing mediator in an in vitro scratch assay. Exp Eye Res 2014;125:183–92.
  • Zucchini N, de Sousa G, Bailly-Maitre B, et al. Regulation of Bcl-2 and Bcl-xL anti-apoptotic protein expression by nuclear receptor PXR in primary cultures of human and rat hepatocytes. Biochim Biophys Acta Mol Cell Res 2005;1745:48–58.
  • 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. Biorg Med Chem 2017;25:1496–513.
  • Suleimen YM, Jose RA, Suleimen RN, et al. Jusanin, a new flavonoid from artemisia commutata with an in silico inhibitory potential against the SARS-CoV-2 main protease. Molecules 2022;27:1636.
  • Mohammed SO, El Ashry ESH, Khalid A, et al. Expression, purification, and comparative inhibition of helicobacter pylori urease by regio-selectively alkylated benzimidazole 2-thione derivatives. Molecules 2022;27:865.
  • Jo S, Kim T, Iyer VG, Im W. CHARMM-GUI: a web-based graphical user interface for CHARMM. J Comput Chem 2008;29:1859–65.
  • Brooks BR, Brooks CL, III, Mackerell AD, Jr, et al. CHARMM: the biomolecular simulation program. J Comput 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 Theor Comput 2016;12:405–13.
  • Best RB, Zhu X, Shim J, et al. Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone phi, psi and side-chain chi(1) and chi(2) dihedral angles. J Chem Theor Comput 2012;8:3257–73.
  • Phillips JC, Braun R, Wang W, et al. Scalable molecular dynamics with NAMD. J Comput Chem 2005;26:1781–802.