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Research Papers

Design and synthesis of thiazolidine-2,4-diones hybrids with 1,2-dihydroquinolones and 2-oxindoles as potential VEGFR-2 inhibitors: in-vitro anticancer evaluation and in-silico studies

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Pages 1903-1917 | Received 18 Mar 2022, Accepted 29 May 2022, Published online: 08 Jul 2022

References

  • Abd El-Mageed MM, Eissa AA, Farag AE-S, Osman EEA. Design and synthesis of novel furan, furo [2, 3-d] pyrimidine and furo [3, 2-e][1, 2, 4] triazolo [1, 5-c] pyrimidine derivatives as potential VEGFR-2 inhibitors. Bioorg Chem 2021;116:105336.
  • El-Sayed AA, Nossier ES, Almehizia AA, Amr AE-GE. Design, synthesis, anticancer evaluation and molecular docking study of novel 2, 4-dichlorophenoxymethyl-based derivatives linked to nitrogenous heterocyclic ring systems as potential CDK-2 inhibitors. J Mol Struct 2022;1247:131285.
  • Chaudhari P, Bari S, Surana S, et al. Logical synthetic strategies and structure-activity relationship of indolin-2-one hybrids as small molecule anticancer agents: an overview. J Mol Struct 2022;1247:131280.
  • 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.
  • Alsaif NA, Taghour MS, Alanazi MM, et al. Identification of new [1, 2, 4] triazolo [4, 3-a] quinoxalines as potent VEGFR-2 tyrosine kinase inhibitors: design, synthesis, anticancer evaluation, and in silico studies. Bioorg Med Chem 2021;46:116384.
  • Elrazaz EZ, Serya RA, Ismail NS, et al. Discovery of potent thieno [2, 3-d] pyrimidine VEGFR-2 inhibitors: design, synthesis and enzyme inhibitory evaluation supported by molecular dynamics simulations. Bioorg Chem 2021;113:105019.
  • Mohamed TK, Batran RZ, Elseginy SA, et al. Synthesis, anticancer effect and molecular modeling of new thiazolylpyrazolyl coumarin derivatives targeting VEGFR-2 kinase and inducing cell cycle arrest and apoptosis. Bioorg Chem 2019;85:253–73.
  • 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.
  • Guo S, Colbert LS, McGlothen TZ, Gonzalez-Perez RR. Regulation of angiogenesis in human cancer via vascular endothelial growth factor receptor-2 (VEGFR-2). Tumor Angiogenesis 2012;2012:27–66.
  • Modi SJ, Kulkarni VM. Vascular endothelial growth factor receptor (VEGFR-2)/KDR inhibitors: medicinal chemistry perspective. Med Drug Discovery 2019;2:100009.
  • Huang Y, Chen X, Dikov MM, et al. Distinct roles of VEGFR-1 and VEGFR-2 in the aberrant hematopoiesis associated with elevated levels of VEGF. Blood J Am Soc Hematol 2007;110:624–31.
  • 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.
  • Wang Z, Wang N, Han S, et al. Dietary compound isoliquiritigenin inhibits breast cancer neoangiogenesis via VEGF/VEGFR-2 signaling pathway. PLoS One 2013;8:e68566.
  • 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.
  • Xie Q-Q, Xie H-Z, Ren J-X, et al. Pharmacophore modeling studies of type I and type II kinase inhibitors of Tie2. J Mol Graph Model 2009;27:751–8.
  • 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.
  • Eskander RN, Tewari KS. Incorporation of anti-angiogenesis therapy in the management of advanced ovarian carcinoma—mechanistics, review of phase III randomized clinical trials, and regulatory implications. Gynecol Oncol 2014;132:496–505.
  • Abdel-Aziz HA, Ghabbour HA, Eldehna WM, et al. Synthesis, crystal structure, and biological activity of cis/trans amide rotomers of (Z)-N′-(2-Oxoindolin-3-ylidene) formohydrazide. J Chem 2014;2014:1–7.
  • Eldehna WM, Al-Wabli RI, Almutairi MS, et al. Synthesis and biological evaluation of certain hydrazonoindolin-2-one derivatives as new potent anti-proliferative agents. J Enzyme Inhib Med Chem 2018;33:867–78.
  • Attia MI, Eldehna WM, Afifi SA, et al. New hydrazonoindolin-2-ones: synthesis, exploration of the possible anti-proliferative mechanism of action and encapsulation into PLGA microspheres. PloS One 2017;12:e0181241.
  • Mohamady S, Galal M, Eldehna WM, et al. Dual targeting of VEGFR2 and C-met kinases via the design and synthesis of substituted 3-(Triazolo-thiadiazin-3-yl) indolin-2-one derivatives as angiogenesis inhibitors. ACS Omega 2020;5:18872–86.
  • Eldehna WM, Abo-Ashour MF, Al-Warhi T, et al. Development of 2-oxindolin-3-ylidene-indole-3-carbohydrazide derivatives as novel apoptotic and anti-proliferative agents towards colorectal cancer cells. J Enzyme Inhib Med Chem 2021;36:320–9.
  • Prakash CR, Raja S. Indolinones as promising scaffold as kinase inhibitors: a review. Mini Rev Med Chem 2012;12:98–119.
  • Zou H, Zhang L, Ouyang J, et al. Synthesis and biological evaluation of 2-indolinone derivatives as potential antitumor agents. Eur J Med Chem 2011;46:5970–7.
  • Fang Y, Wu Z, Xiao M, et al. Design, synthesis, and evaluation of new 2-oxoquinoline arylaminothiazole derivatives as potential anticancer agents. Bioorg Chem 2021;106:104469.
  • Bonnefous C, Payne JE, Roppe J, et al. Discovery of inducible nitric oxide synthase (iNOS) inhibitor development candidate KD7332, part 1: identification of a novel, potent, and selective series of quinolinone iNOS dimerization inhibitors that are orally active in rodent pain models. J Med Chem 2009;52:3047–62.
  • Ohashi T, Oguro Y, Tanaka T, et al. Discovery of pyrrolo [3, 2-c] quinoline-4-one derivatives as novel hedgehog signaling inhibitors. Bioorg Med Chem 2012;20:5496–506.
  • Suthar SK, Jaiswal V, Lohan S, et al. Novel quinolone substituted thiazolidin-4-ones as anti-inflammatory, anticancer agents: design, synthesis and biological screening. Eur J Med Chem 2013;63:589–602.
  • Banu S, Bollu R, Bantu R, et al. Design, synthesis and docking studies of novel 1, 2-dihydro-4-hydroxy-2-oxoquinoline-3-carboxamide derivatives as a potential anti-proliferative agents. Eur J Med Chem 2017;125:400–10.
  • Yu Y-C, Kuang W-B, Huang R-Z, et al. Design, synthesis and pharmacological evaluation of new 2-oxo-quinoline derivatives containing α-aminophosphonates as potential antitumor agents. MedChemComm 2017;8:1158–72.
  • Shankar S, Vuppu S. In vitro drug metabolism and pharmacokinetics of a novel thiazolidinedione derivative, a potential anticancer compound. J Pharma Biomed Anal 2020;179:113000.
  • Sharma P, Reddy TS, Kumar NP, et al. Conventional and microwave-assisted synthesis of new 1H-benzimidazole-thiazolidinedione derivatives: a potential anticancer scaffold. Eur J Med Chem 2017;138:234–45.
  • Joshi H, Patil V, Tilekar K, et al. Benzylidene thiazolidinediones: synthesis, in vitro investigations of antiproliferative mechanisms and in vivo efficacy determination in combination with Imatinib. Bioorg Med Chem Lett 2020;30:127561.
  • 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.
  • 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.
  • 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;45:16557–71.
  • Alanazi MM, Elkady H, Alsaif NA, et al. New quinoxaline-based VEGFR-2 inhibitors: design, synthesis, and antiproliferative evaluation with in silico docking, ADMET, toxicity, and DFT studies. RSC Adv 2021;11:30315–28.
  • 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-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, Elkady H, Alsaif NA, et al. Discovery of new quinoxaline-based derivatives as anticancer agents and potent VEGFR-2 inhibitors: design, synthesis, and in silico study. J Mol Struct 2022;1253:132220.
  • Elkady H, Elwan A, El-Mahdy HA, et al. New benzoxazole derivatives as potential VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, anti-proliferative evaluation, flowcytometric analysis, and in silico studies. J Enzyme Inhib Med Chem 2022;37:397–410.
  • 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.
  • Laxmikeshav K, Kumari P, Shankaraiah N. Expedition of sulfur‐containing heterocyclic derivatives as cytotoxic agents in medicinal chemistry: a decade update. Med Res Rev 2022;42:513–75.
  • Yadav U, Vanjari Y, Laxmikeshav K, et al. Synthesis and in vitro cytotoxicity evaluation of phenanthrene linked 2, 4-thiazolidinediones as potential anticancer agents. Anti-Cancer Agents Med Chem 2021;21:1127–40.
  • Tokala R, Thatikonda S, Sana S, et al. Synthesis and in vitro cytotoxicity evaluation of β-carboline-linked 2, 4-thiazolidinedione hybrids: potential DNA intercalation and apoptosis-inducing studies. New J Chem 2018;42: 16226–36.
  • Sharma P, Reddy TS, Thummuri D, et al. Synthesis and biological evaluation of new benzimidazole-thiazolidinedione hybrids as potential cytotoxic and apoptosis inducing agents. Eur J Med Chem 2016;124:608–21.
  • Hou T, Zhu L, Chen L, Xu X. Mapping the binding site of a large set of quinazoline type EGF-R inhibitors using molecular field analyses and molecular docking studies. J Chem Inform Comput Sci 2003;43:273–87.
  • Kar K, Krithika U, Basu P, et al. Design, synthesis and glucose uptake activity of some novel glitazones. Bioorg Chem 2014;56:27–33.
  • Abdel-Wahab BF, Khidre RE. 2-Chloroquinoline-3-carbaldehyde II: synthesis, reactions, and applications. J Chem 2013;2013:1–13.
  • Bruno G, Costantino L, Curinga C, et al. Synthesis and aldose reductase inhibitory activity of 5-arylidene-2, 4-thiazolidinediones. Bioorg Med Chem 2002;10:1077–84.
  • Evdokimov NM, Magedov IV, McBrayer D, Kornienko A. Isatin derivatives with activity against apoptosis-resistant cancer cells. Bioorg Med Chem Lett 2016;26:1558–60.
  • 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 ati-HHV-6 agents. 7th edition; 2014. Pages 311–331.
  • 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. Validation of in-vitro bioassay methods: application in herbal drug research. Profiles Drug Subst Excip Related 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. Nature Protocols 2007;2:329–33.
  • D’Anselmi F, Valerio M, Cucina A, et al. Metabolism and cell shape in cancer: a fractal analysis. Int J Biochem Cell Biol 2011;43:1052–8.
  • 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.
  • 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.
  • 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 Der Pharmazie 2019;352:1800387.
  • 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.
  • Miller BR, III, McGee TD, Jr, Swails JM, et al. MMPBSA. PY: an efficient program for end-state free energy calculations. J Chem Theory Comput 2012;8:3314–21.
  • Wang E, Sun H, Wang J, et al. End-point binding free energy calculation with MM/PBSA and MM/GBSA: strategies and applications in drug design. Chem Rev 2019;119:9478–508.
  • Genheden S, Ryde U. The MM/PBSA and MM/GBSA methods to estimate ligand-binding affinities. Expert Opin Drug Discov 2015;10:449–61.
  • Hou T, Wang J, Li Y, Wang W. Assessing the performance of the MM/PBSA and MM/GBSA methods. 1. The accuracy of binding free energy calculations based on molecular dynamics simulations. J Chem Informat Model 2011;51:69–82.
  • Xia X, Maliski EG, Gallant P, Rogers D. Classification of kinase inhibitors using a Bayesian model. J Med Chem 2004;47:4463–70.
  • BIOVIA QSAR, ADMET and predictive toxicology. https://www.3dsbiovia.com/products/collaborative-science/biovia-discovery-studio/qsar-admet-and-predictive-toxicology.html [last accessed May 2020].
  • 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;101:95–99.
  • 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. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research 2005;1745:48–58.
  • 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.
  • 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.
  • 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.
  • 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.
  • Elkaeed EB, Elkady H, Belal A, et al. Multi-phase in silico discovery of potential SARS-CoV-2 RNA-dependent rna polymerase inhibitors among 3009 clinical and FDA-approved related drugs. Processes 2022;10:530.
  • 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.
  • 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 Theory Comput 2012;8:3257–73.
  • Phillips JC, Braun R, Wang W, et al. Scalable molecular dynamics with NAMD. J Computat Chem 2005;26:1781–802.
  • 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.
  • 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.
  • 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.
  • Alesawy MS, Elkaeed EB, Alsfouk AA, et al. In silico screening of semi-synthesized compounds as potential inhibitors for SARS-CoV-2 papain-like protease: pharmacophoric features, molecular docking, ADMET, toxicity and DFT studies. Molecules 2021;26:6593.
  • 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.