2,229
Views
11
CrossRef citations to date
0
Altmetric
Research Papers

Discovery of new nicotinamides as apoptotic VEGFR-2 inhibitors: virtual screening, synthesis, anti-proliferative, immunomodulatory, ADMET, toxicity, and molecular dynamic simulation studies

, , ORCID Icon, , , , , ORCID Icon, & ORCID Icon show all
Pages 1389-1403 | Received 24 Feb 2022, Accepted 21 Apr 2022, Published online: 16 May 2022

References

  • Liang P, Ballou B, Lv X, et al. Monotherapy and combination therapy using anti‐angiogenic nanoagents to fight cancer. Adv Mater 2021;33:1389.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Zhong H-T, Yu Y-Z, Velasco C. Molecular insights probing Bismurrayaquinone A as an angiogenesis inhibitor via inhibition of VEGFR-2 Kinase domain. Citeseer 2011;1(4):95–100.
  • Lugano R, Ramachandran M, Dimberg A. Tumor angiogenesis: causes, consequences, challenges and opportunities. Cell Mol Life Sci 2020;77:1745–70.
  • Hunter T. The role of tyrosine phosphorylation in cell growth. In: The Harvey Lectures Series 94, 1998–1999. Vol. 94; 2000:81.
  • Claesson‐Welsh L, Welsh M. VEGFA and tumour angiogenesis. J Intern Med 2013;273:114–27.
  • 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-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.
  • 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-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.
  • Yousef RG, Sakr HM, Eissa IH, et al. New quinoxaline-2 (1 H)-ones as potential VEGFR-2 inhibitors: design, synthesis, molecular docking, ADMET profile and anti-proliferative evaluations. N J Chem 2021;45:16949–64.
  • 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.
  • 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.
  • Alanazi MM, Elwan A, Alsaif NA, et al. Discovery of new 3-methylquinoxalines as potential anti-cancer agents and apoptosis inducers targeting VEGFR-2: design, synthesis, and in silico studies. J Enzyme Inhib Med Chem 2021;36:1732–50.
  • 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.
  • Oguro Y, Cary DR, Miyamoto N, et al. Design, synthesis, and evaluation of novel VEGFR2 kinase inhibitors: discovery of [1,2,4]triazolo[1,5-a]pyridine derivatives with slow dissociation kinetics. Bioorg Med Chem 2013;21:4714–29.
  • AbdelHaleem A, Mansour AO, AbdelKader M, Arafa RK. Selective VEGFR-2 inhibitors: synthesis of pyridine derivatives, cytotoxicity and apoptosis induction profiling. Bioorg Chem 2020;103:104222.
  • Gu W, Dai Y, Qiang H, et al. Discovery of novel 2-substituted-4-(2-fluorophenoxy) pyridine derivatives possessing pyrazolone and triazole moieties as dual c-Met/VEGFR-2 receptor tyrosine kinase inhibitors. Bioorg Chem 2017;72:116–22.
  • 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. Biorg. 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.
  • Xia X, Maliski EG, Gallant P, Rogers D. Classification of kinase inhibitors using a Bayesian model. J Med Chem 2004;47:4463–70.
  • Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983;65:55–63.
  • Cai SX, Nguyen B, Jia S, et al. Discovery of substituted N-phenyl nicotinamides as potent inducers of apoptosis using a cell- and caspase-based high throughput screening assay. J Med Chem 2003;46:2474–81.
  • Sousa SF, Fernandes PA, Ramos MJ. Protein-ligand docking: current status and future challenges. Proteins: Struct Funct Bioinform 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. Curr Opin Struct Biol 2002;12:190–6.
  • Durrant JD, McCammon JA. Molecular dynamics simulations and drug discovery. BMC Biol 2011;9:71–9.
  • Ren J, Yuan X, Li J, et al. Assessing the performance of the g_mmpbsa tools to simulate the inhibition of oseltamivir to influenza virus neuraminidase by molecular mechanics Poisson–Boltzmann surface area methods. J Chinese Chem Soc 2020;67:46–53.
  • 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. Bioorganic Chem 2019;91:103115.
  • 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.
  • Gerlier D, Thomasset N. Use of MTT colorimetric assay to measure cell activation. J Immunol Methods 1986;94:57–63.
  • 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-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.
  • Andersson M, Sjöstrand J, Petersen A, et al. Caspase and proteasome activity during staurosporin-induced apoptosis in lens epithelial cells. Invest Ophthalmol Vis Sci 2000;41:2623–32.
  • Emily H-YC, Wei MC, Weiler S, et al. BCL-2, BCL-XL sequester BH3 domain-only molecules preventing BAX-and BAK-mediated mitochondrial apoptosis. Mol Cell 2001;8:705–11.
  • Léonce S, Pérez V, Lambel S, et al. Induction of cyclin E and inhibition of DNA synthesis by the novel acronycine derivative S23906-1 precede the irreversible arrest of tumor cells in S phase leading to apoptosis. Mol Pharmacol 2001;60:1383–91.
  • Eldehna WM, El Hassab MA, Abo-Ashour MF, et al. Development of isatin-thiazolo[3,2-a]benzimidazole hybrids as novel CDK2 inhibitors with potent in vitro apoptotic anti-proliferative activity: synthesis, biological and molecular dynamics investigations Bioorg Chem 2021;110:104748.
  • 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.
  • 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.
  • 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.
  • Al-Warhi T, Abo-Ashour MF, Almahli H, et al. Novel [(N-alkyl-3-indolylmethylene)hydrazono]oxindoles arrest cell cycle and induce cell apoptosis by inhibiting CDK2 and Bcl-2: synthesis, biological evaluation and in silico studies. J Enzyme Inhib Med Chem 2020;35:1300–9.
  • Talaat RM. Soluble angiogenesis factors in sera of Egyptian patients with hepatitis C virus infection: correlation with disease severity. Viral Immunol 2010;23:151–7.
  • 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
  • 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 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 Theory Comput 2016;12:405–13.