Anti-cancer and immunomodulatory evaluation of new nicotinamide derivatives as potential VEGFR-2 inhibitors and apoptosis inducers: in vitro and in silico studies

References

• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin 2020;70:7–30.
   PubMed Web of Science ®Google Scholar
• Fabbro D, Parkinson D, Matter A. Protein tyrosine kinase inhibitors: new treatment modalities? Curr Opin Pharmacol 2002;2:374–81.
   PubMed Web of Science ®Google Scholar
• Abdallah AE, Mabrouk RR, Al Ward MMS, et al. Synthesis, biological evaluation, and molecular docking of new series of antitumor and apoptosis inducers designed as VEGFR-2 inhibitors. J Enzyme Inhib Med Chem 2022;37:573–91.
   PubMed Web of Science ®Google Scholar
• Phillips CM, Lima EA, Woodall RT, et al. A hybrid model of tumor growth and angiogenesis: in silico experiments. PLoS One 2020;15:e0231137.
   PubMed Web of Science ®Google Scholar
• Patel HM, Bari P, Karpoormath R, et al. Design and synthesis of VEGFR-2 tyrosine kinase inhibitors as potential anticancer agents by virtual based screening. RSC Adv 2015;5:56724–71.
   Web of Science ®Google Scholar
• Shibuya M. Vascular endothelial growth factor and its receptor system: physiological functions in angiogenesis and pathological roles in various diseases. J Biochem 2013;153:13–9.
   PubMed Web of Science ®Google Scholar
• Frezzetti D, Gallo M, Roma C, et al. Vascular endothelial growth factor a regulates the secretion of different angiogenic factors in lung cancer cells. J Cell Physiol 2016;231:1514–21.
   PubMed Web of Science ®Google Scholar
• Stuttfeld E, Ballmer‐Hofer K. Structure and function of VEGF receptors. IUBMB Life 2009;61:915–22.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Shahin MI, Abou El Ella DA, Ismail NS, Abouzid KA. Design, synthesis and biological evaluation of type-II VEGFR-2 inhibitors based on quinoxaline scaffold. Bioorg Chem 2014;56:16–26.
   PubMed Web of Science ®Google Scholar
• Yousef RG, Ibrahim A, Khalifa MM, et al. Discovery of new nicotinamides as apoptotic VEGFR-2 inhibitors: virtual screening, synthesis, anti-proliferative, immunomodulatory, ADMET, toxicity, and molecular dynamic simulation studies. J Enzyme Inhib Med Chem 2022;37:1389–403.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMedGoogle Scholar
• Dunlop RJ, Campbell CW. Cytokines and advanced cancer. J Pain Symptom Manage 2000;20:214–32.
   PubMed Web of Science ®Google Scholar
• Michalaki V, Syrigos K, Charles P, Waxman J. Serum levels of IL-6 and TNF-α correlate with clinicopathological features and patient survival in patients with prostate cancer. Br J Cancer 2004;90:2312–6.
   PubMed Web of Science ®Google Scholar
• Taher MY, Davies DM, Maher J. The role of the interleukin (IL)-6/IL-6 receptor axis in cancer. Biochem Soc Trans 2018;46:1449–62.
   PubMed Web of Science ®Google Scholar
• Balkwill FJC. TNF-alpha in promotion and progression of cancer. Cancer Metastasis Rev 2006;25:409–16.
   PubMed Web of Science ®Google Scholar
• Ungerstedt JS, Blombäck M, Söderström T. Nicotinamide is a potent inhibitor of proinflammatory cytokines. Clin Exp Immunol 2003;131:48–52.
   PubMed Web of Science ®Google Scholar
• Zeidan MA, Mostafa AS, Gomaa RM, et al. Design, synthesis and docking study of novel picolinamide derivatives as anticancer agents and VEGFR-2 inhibitors. Eur J Med Chem 2019;168:315–29.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   Web of Science ®Google Scholar
• Zhang Q, Li J, Zhong H, Xu Y. The mechanism of nicotinamide on reducing acute lung injury by inhibiting MAPK and NF-κB signal pathway. Mol Med 2021;27:1–11.
   PubMed Web of Science ®Google Scholar
• Grange PA, Raingeaud J, Calvez V, Dupin N. Nicotinamide inhibits propionibacterium acnes-induced IL-8 production in keratinocytes through the NF-κB and MAPK pathways. J Dermatol Sci 2009;56:106–12.
   PubMed Web of Science ®Google Scholar
• He MM, Smith AS, Oslob JD, et al. Small-molecule inhibition ofTNF-a. Science 2005;310:1022–5.
   PubMed Web of Science ®Google Scholar
• Zia K, Ashraf S, Jabeen A, et al. Identification of potential TNF-α inhibitors: from in silico to in vitro studies. Sci Rep 2020;10:1–9.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• El-Adl K, El-Helby A-GA, Sakr H, Elwan A. [1, 2, 4] Triazolo [4, 3-a] quinoxaline and [1, 2, 4] triazolo [4, 3-a] quinoxaline-1-thiol-derived DNA intercalators: design, synthesis, molecular docking, in silico ADMET profiles and anti-proliferative evaluations. N J Chem 2021;45:881–97.
   Web of Science ®Google Scholar
• El-Adl K, El-Helby A-GA, Sakr H, Elwan A. Design, synthesis, molecular docking and anti-proliferative evaluations of [1, 2, 4] triazolo [4, 3-a]. Quinoxaline Derivatives as DNA Intercalators and Topoisomerase II Inhibitors. Bioorg Chem 2020;105:104399.
   PubMed Web of Science ®Google Scholar
• Chan KT, Meng FY, Li Q, et al. Cucurbitacin B induces apoptosis and S phase cell cycle arrest in BEL-7402 human hepatocellular carcinoma cells and is effective via oral administration. Cancer Letters 2010;294:118–24.
   PubMed Web of Science ®Google Scholar
• Sobhy MK, Mowafy S, Lasheen DS, et al. 3D-QSAR pharmacophore modelling, virtual screening and docking studies for lead discovery of a novel scaffold for VEGFR 2 inhibitors: design, synthesis and biological evaluation. Bioorg Chem 2019;89:102988.
   PubMed Web of Science ®Google Scholar
• Mena-Ulecia K, Tiznado W, Caballero J. Study of the differential activity of thrombin inhibitors using docking, QSAR, molecular dynamics, and MM-GBSA. PLoS One 2015;10:e0142774.
   PubMed Web of Science ®Google Scholar
• Wang S-Q, Shi M, Fang L, et al. Design of dual inhibitors of human TNF-α and IL-6 with potentials for the treatment of rheumatoid arthritis. Trop J Pharm Res 2019;18:2305–12.
   Web of Science ®Google Scholar
• Sousa SF, Fernandes PA, Ramos MJ. Protein–ligand docking: current status and future challenges. Proteins: Struct Funct Bioinformatics 2006;65:15–26.
   PubMed Web of Science ®Google Scholar
• Hollingsworth SA, Dror RO. Molecular dynamics simulation for all. Neuron 2018;99:1129–43.
   PubMed Web of Science ®Google Scholar
• Hansson T, Oostenbrink C, van Gunsteren W. Molecular dynamics simulations. Curr Opin Struct Biol 2002;12:190–6.
   PubMed Web of Science ®Google Scholar
• Durrant JD, McCammon JA. Molecular dynamics simulations and drug discovery. BMC Biol 2011;9:1–9.
   PubMed Web of Science ®Google Scholar
• Genheden S, Ryde U. The MM/PBSA and MM/GBSA methods to estimate ligand-binding affinities. Expert Opin Drug Discov 2015;10:449–61.
   PubMed Web of Science ®Google Scholar
• Chaitra G, Rohini R. Synthesis and biological activities of [1, 3]‐oxazine derivatives. Der Pharma Chem 2018;10:96–101.
   Google Scholar
• Eldehna WM, Al-Rashood ST, Al-Warhi T, et al. Novel oxindole/benzofuran hybrids as potential dual CDK2/GSK-3β inhibitors targeting breast cancer: design, synthesis, biological evaluation, and in silico studies. J Enzyme Inhib Med Chem 2021;36:270–85.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar