Design, synthesis, molecular modeling and biological evaluation of novel Benzoxazole-Benzamide conjugates via a 2-Thioacetamido linker as potential anti-proliferative agents, VEGFR-2 inhibitors and apoptotic inducers

References

• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J. Clin 2020;70:1587–30.
   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
• Wu C, Wang M, Tang Q, et al. Design, synthesis, activity and docking study of sorafenib analogs bearing sulfonylurea unit. Molecules 2015;20:19361–71.
   PubMed Web of Science ®Google Scholar
• Baudino TA. Targeted cancer therapy: the next generation of cancer treatment. Curr Drug Discov Technol 2015;12:3–20.
   PubMedGoogle Scholar
• Topcul M, Cetin I. Endpoint of cancer treatment: targeted therapies, Asian Pac. Asian Pac J Cancer Prev 2014;15:4395–403.
   PubMedGoogle Scholar
• Qin S, Li A, Yi M, et al. Recent advances on anti-angiogenesis receptor tyrosine kinase inhibitors in cancer therapy. J Hematol Oncol 2019;12:27–37.
   PubMed Web of Science ®Google Scholar
• Edlich F. BCL-2 proteins and apoptosis: recent insights and unknowns. Biochem Biophys Res Commun 2018;500:26–34.
   PubMed Web of Science ®Google Scholar
• Hata AN, Engelman JA, Faber AC. The BCL2 family: key mediators of the apoptotic response to targeted anticancer therapeutics. Cancer Discov 2015;5:475–87.
   PubMed Web of Science ®Google Scholar
• Marone M, Ferrandina G, Macchia G, et al. Bcl-2, Bax, Bcl-x(L) and Bcl-x(S) expression in neoplastic and normal endometrium. Oncology 2000;58:161–8.
   PubMed Web of Science ®Google Scholar
• Lugano R, Ramachandran M, Dimberg A. Tumor angiogenesis: causes, consequences, challenges and opportunities. Cell Mol Life Sci 2020;77:1745–70.
   PubMed Web of Science ®Google Scholar
• Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1995;1:27–31.
   PubMed Web of Science ®Google Scholar
• Karamysheva AF. Mechanisms of angiogenesis. Biochemistry 2008;73:751–62.
   PubMed Web of Science ®Google Scholar
• Kerbel RS. Tumor angiogenesis: past, present and the near future. Carcinogenesis 2000;21:505–15.
   PubMed Web of Science ®Google Scholar
• Ahmed MF, Santali EY, El-Haggar R. Novel piperazine-chalcone hybrids and related pyrazoline analogs targeting VEGFR-2 kinase; design, synthesis, molecular docking studies, and anticancer evaluation. J. Enzy. Inhib. Med. Chem 2021;36:307–18.
   PubMed Web of Science ®Google Scholar
• Modi SJ, Kulkarni VM. Vascular Endothelial Growth Factor Receptor (VEGFR-2)/KDR inhibitors: medicinal chemistry perspective. Med Drug Discov 2019;2:100009.
   Google Scholar
• Potashman MH, Bready J, Coxon A, et al. Design, synthesis, and evaluation of orally active benzimidazoles and benzoxazoles as vascular endothelial growth factor-2 receptor tyrosine kinase inhibitors. J Med Chem 2007;50:4351–73.
   PubMed Web of Science ®Google Scholar
• Yuan X, Yang Q, Liu T, et al. Design, synthesis and in vitro evaluation of 6-amide-2-aryl benzoxazole/benzimidazole derivatives against tumor cells by inhibiting VEGFR-2 kinase. Eur J Med Chem 2019;179:147–65.
   PubMed Web of Science ®Google Scholar
• DR, Green Means to an end: apoptosis and other cell death mechanisms. New York: Cold Spring Harbor, Cold Spring Harbor Laboratory Press; 2011.
   Google Scholar
• Spierings D, McStay G, Saleh M, et al. Connected to death: the (unexpurgated) mitochondrial pathway of apoptosis. Science 2005;310:66–7.
   PubMed Web of Science ®Google Scholar
• Wang B, Xu A. Aryl hydrocarbon receptor pathway participates in myocardial ischemia reperfusion injury by regulating mitochondrial apoptosis. Med Hypotheses 2019;123:2–5.
   PubMed Web of Science ®Google Scholar
• Modugno M, Banfi P, Gasparri F, et al. Mcl-1 antagonism is a potential therapeutic strategy in a subset of solid cancers. Exp Cell Res 2015;332:267–77.
   PubMed Web of Science ®Google Scholar
• Placzek WJ, Wei J, Kitada S, et al. A survey of the anti-apoptotic Bcl-2 subfamily expression in cancer types provides a platform to predict the efficacy of Bcl-2 antagonists in cancer therapy. Cell Death Dis 2010;1:e40.
   PubMed Web of Science ®Google Scholar
• 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 Enzy Inhib Med Chem 2021;36:319–28.
   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
• Chen G, Liu Z, Zhang Y, et al. Synthesis and anti-inflammatory evaluation of novel benzimidazole and imidazopyridine derivatives. ACS Med Chem Lett 2013;4:69–74.
   PubMed Web of Science ®Google Scholar
• Kakkar S, Narasimhan B. A comprehensive review on biological activities of oxazole derivatives. BMC Chem 2019;13:1–24.
   PubMed Web of Science ®Google Scholar
• Mohamed MS, Rashad AE, Adbel-Monem M, Fatahalla SS. New anti-inflammatory agents. Z Naturforsch C J Biosci 2007;62:27–31.
   PubMed Web of Science ®Google Scholar
• Veerasamy R, Roy A, Karunakaran R, Rajak H. Structure-activity relationship analysis of benzimidazoles as emerging anti-inflammatory agents: an overview. Pharmaceuticals 2021;14:663–93.
   Web of Science ®Google Scholar
• Seth K, Garg SK, Kumar R, et al. Chakraborti, 2-(2-Arylphenyl)benzoxazole As a Novel Anti-Inflammatory Scaffold: Synthesis and Biological Evaluation. ACS Med Chem Lett 2014;5:512–6.
   PubMed Web of Science ®Google Scholar
• Balaswamy G, Pradeep P, Srinivas K, Rajakomuraiah T. Synthesis, characterization and anti-microbial activity of new series of benzoxazole derivatives. Int J Chem Sci 2012;10:1830–6.
   Google Scholar
• Gamba E, Mori M, Kovalenko L, et al. Identification of novel 2-benzoxazolinone derivatives with specific inhibitory activity against the HIV-1 nucleocapsid protein. Eur J Med Chem 2018;145:154–64.
   PubMed Web of Science ®Google Scholar
• Rida SM, Ashour FA, El-Hawash SA, et al. Synthesis of some novel benzoxazole derivatives as anticancer, anti-HIV-1 and antimicrobial agents. Eur J Med Chem 2005;40:949–59.
   PubMed Web of Science ®Google Scholar
• Zeyrek CT, Arpacı ÖT, Arısoy M, Onurdağ FK. Synthesis, antimicrobial activity, density functional modelling and molecular docking with COVID-19 main protease studies of benzoxazole derivative: 2-(p-chloro-benzyl)-5-[3-(4-ethly-1-piperazynl) propionamido]-benzoxazole. J Mol Struct 2021;1237:130413.
   PubMed Web of Science ®Google Scholar
• Bhole RP, Chikhale RV, Wavhale RD, et al. Design, synthesis and evaluation of novel enzalutamide analogues as potential anticancer agents. Heliyon 2021;7:e06227.
   PubMed Web of Science ®Google Scholar
• Bradshaw TD, Westwell AD. The development of the antitumour benzothiazole prodrug, Phortress, as a clinical candidate. Curr Med Chem 2004;11:1009–21.
   PubMed Web of Science ®Google Scholar
• Dadashpour S, Kucukkilinc TT, Ercan A, et al. Synthesis and anticancer activity of benzimidazole/benzoxazole substituted triazolotriazines in hepatocellular carcinoma. Anticancer Agents Med Chem 2019;19:2120–9.
   PubMed Web of Science ®Google Scholar
• Desai S, Desai V, Shingade S. In-vitro Anti-cancer assay and apoptotic cell pathway of newly synthesized benzoxazole-N-heterocyclic hybrids as potent tyrosine kinase inhibitors. Bioorg Chem 2020;94:103382.
   PubMed Web of Science ®Google Scholar
• Dhadda S, Kumar A, Kamlesh R, et al. Benzothiazoles: From recent advances in green synthesis to anti-cancer potential. Sustain Chem Phar 2021;24:100521.
   Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• El-Hady HA, Abubshait SA. Synthesis and anticancer evaluation of imidazolinone and benzoxazole derivatives. Arab J Chem 2017;10:S3725–S3731.
   Web of Science ®Google Scholar
• El-Hameed RHA, Fatahala SS, Sayed AI. Synthesis of some novel benzimidazole derivatives as anticancer agent, and evaluation for CDK2 inhibition activity. Med Chem 2022;18:1–11.
   Web of Science ®Google Scholar
• Mantzourani C, Gkikas D, Kokotos A, et al. Synthesis of benzoxazole-based vorinostat analogs and their antiproliferative activity. Bioorg Chem 2021;114:105132.
   PubMed Web of Science ®Google Scholar
• Osmaniye D, Korkut Çelikateş B, Sağlık BN, et al. Synthesis of some new benzoxazole derivatives and investigation of their anticancer activities. Eur J Med Chem 2021;210:112979.
   PubMed Web of Science ®Google Scholar
• Xiang P, Zhou T, Wang L, et al. Novel benzothiazole, benzimidazole and benzoxazole derivatives as potential antitumor agents: synthesis and preliminary in vitro biological evaluation. Molecules 2012;17:873–83.
   PubMed Web of Science ®Google Scholar
• Khajondetchairit P, Phuangsawai O, Suphakun P, et al. Design, synthesis, and evaluation of the anticancer activity of 2-amino-aryl-7-aryl-benzoxazole compounds. Chem Biol Drug Des 2017;90:987–94.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Lee K, Jeong KW, 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
• Xie QQ, Xie HZ, Ren JX, et al. Pharmacophore modeling studies of type I and type II kinase inhibitors of Tie2. J Mol Graph Model 2009;27:751–8.
   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
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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. Synthetic Commun 2007;37:2457–60.
   Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   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
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Chikhale R, Thorat S, Choudhary RK, et al. Design, synthesis and anticancer studies of novel aminobenzazolyl pyrimidines as tyrosine kinase inhibitors. Bioorg Chem 2018;77:84–100.
   PubMed Web of Science ®Google Scholar
• Stevens MF, McCall CJ, Lelieveld P, et al. Structural studies on bioactive compounds. 23. Synthesis of polyhydroxylated 2-phenylbenzothiazoles and a comparison of their cytotoxicities and pharmacological properties with genistein and quercetin. J Med Chem 1994;37:1689–95.
   PubMed Web of Science ®Google Scholar
• Ghoshal T, Patel TM. Anticancer activity of benzoxazole derivative (2015 onwards): a review. Fut J Pharm Sci 2020;6:94–113.
   Web of Science ®Google Scholar
• Omar AME, AboulWafa OM, El-Shoukrofy MS, Amr ME. Benzoxazole derivatives as new generation of anti-breast cancer agents. Bioorg Chem 2020;96:103593.
   PubMed Web of Science ®Google Scholar
• Peng F, Liu D, Zhang Q, et al. VEGFR-2 inhibitors and the therapeutic applications thereof: a patent review (2012-2016). Expert Opin Ther Pat 2017;27:987–1004.
   PubMed Web of Science ®Google Scholar
• Skehan P, Storeng R, Scudiero D, et al. New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst 1990;82:1107–12.
   PubMed Web of Science ®Google Scholar
• Meng XY, Zhang HX, Mezei M, Cui M. Molecular docking: a powerful approach for structure-based drug discovery. Curr Comput Aided Drug Des 2011;7:146–57.
   PubMed Web of Science ®Google Scholar
• Omar AM, El-Araby ME, Abdelghany TM, et al. Introducing of potent cytotoxic novel 2-(aroylamino)cinnamamide derivatives against colon cancer mediated by dual apoptotic signal activation and oxidative stress. Bioorg Chem 2020;101:103953.
   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
• Lo KK, Lee TK, Lau JS, et al. Luminescent biological probes derived from ruthenium(II) estradiol polypyridine complexes. Inorg Chem 2008;47:200–8.
   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
• Burnette WN. "Western blotting": electrophoretic transfer of proteins from sodium dodecyl sulfate-polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem 1981;112:195–203.
   PubMed Web of Science ®Google Scholar
• Available from: http://www.rcsb.org/
   Google Scholar