New benzothiazole hybrids as potential VEGFR-2 inhibitors: design, synthesis, anticancer evaluation, and in silico study

References

• Varmus H. The new era in cancer research. Science. 2006;312(5777):1162–1165.
   PubMed Web of Science ®Google Scholar
• Wang Z, Shi X-H, Wang J, Zhou T, Xu Y-Z, Huang T-T, Li Y-F, Zhao Y-L, Yang L, Yang S-Y. Synthesis, structure–activity relationships and preliminary antitumor evaluation of benzothiazole-2-thiol derivatives as novel apoptosis inducers. Bioorganic Med Chem Lett. 2011;21:1097–1101.
   PubMed Web of Science ®Google Scholar
• Hamdi A, Said E, Farahat AA, Aa El-Bialy S, Am Massoud M. Synthesis and in vivo antifibrotic activity of novel leflunomide analogues. Lett Drug Des Discov. 2016;13:912–920.
   Web of Science ®Google Scholar
• Evan GI, Vousden KH. Proliferation, cell cycle and apoptosis in cancer. Nature. 2001;411(6835):342–348.
   PubMed Web of Science ®Google Scholar
• Branca MA. Multi-kinase inhibitors create buzz at ASCO. Nat Biotechnol. 2005;23(6):639–640.
   PubMed Web of Science ®Google Scholar
• Blankenberg FG. Apoptosis imaging: anti-cancer agents in medicinal chemistry. Anticancer Agents Med Chem. 2009;9(9):944–951.
   PubMed Web of Science ®Google Scholar
• Roskoski R Jr, Classification of small molecule protein kinase inhibitors based upon the structures of their drug-enzyme complexes. Pharmacol Res Commun. 2016;103:26–48.
   Google Scholar
• Fabbro D, Ruetz S, Buchdunger E, Cowan-Jacob SW, Fendrich G, Liebetanz J, Mestan J, O'Reilly T, Traxler P, Chaudhuri B, et al. Protein kinases as targets for anticancer agents: from inhibitors to useful drugs. Pharmacol Ther. 2002;93(2-3):79–98.
   PubMed Web of Science ®Google Scholar
• Mohamed AR, El Kerdawy AM, George RF, Georgey HH, Gawad NMA. Design, synthesis and in silico insights of new 7, 8-disubstituted-1, 3-dimethyl-1H-purine-2, 6 (3H, 7H)-dione derivatives with potent anticancer and multi-kinase inhibitory activities. Bioorg Chem. 2021;107:104569.
   PubMed Web of Science ®Google Scholar
• Drąg-Zalesińska M, Drąg M, Poręba M, Borska S, Kulbacka J, Saczko J. Anticancer properties of ester derivatives of betulin in human metastatic melanoma cells (Me-45). Cancer Cell Int. 2017;17:1–7.
   PubMed Web of Science ®Google Scholar
• El-Sherief HA, Youssif BG, Bukhari SNA, Abdelazeem AH, Abdel-Aziz M, Abdel-Rahman HM. Synthesis, anticancer activity and molecular modeling studies of 1, 2, 4-triazole derivatives as EGFR inhibitors. Eur J Med Chem. 2018;156:774–789.
   PubMed Web of Science ®Google Scholar
• McTigue M, Murray BW, Chen JH, Deng Y-L, Solowiej J, Kania RS. Molecular conformations, interactions, and properties associated with drug efficiency and clinical performance among VEGFR TK inhibitors. Proc Natl Acad Sci U S A. 2012;109(45):18281–18289.
   PubMed Web of Science ®Google Scholar
• Aziz MA, Serya RAT, Lasheen DS, Abdel-Aziz AK, Esmat A, Mansour AM, Singab ANB, Abouzid KAM. Discovery of Potent VEGFR-2 Inhibitors based on Furopyrimidine and Thienopyrimidne Scaffolds as Cancer Targeting Agents. Sci Rep. 2016;6:24460.
   PubMed Web of Science ®Google Scholar
• Mahdy HA, Ibrahim MK, Metwaly AM, Belal A, Mehany ABM, El-Gamal KMA, El-Sharkawy A, Elhendawy MA, Radwan MM, Elsohly MA, 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.
   PubMed Web of Science ®Google Scholar
• Lee K, Jeong K-W, Lee Y, Song JY, Kim MS, Lee GS, Kim Y. Pharmacophore modeling and virtual screening studies for new VEGFR-2 kinase inhibitors. Eur J Med Chem. 2010;45(11):5420–5427.
   PubMed Web of Science ®Google Scholar
• Wang Y, Peng C, Wang G, Xu Z, Luo Y, Wang J, Zhu W. Exploring binding mechanisms of VEGFR2 with three drugs lenvatinib, sorafenib, and sunitinib by molecular dynamics simulation and free energy calculation. Chem Biol Drug Des. 2019;93(5):934–948.
   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
• Wilhelm S, Carter C, Lynch M, Lowinger T, Dumas J, Smith RA, Schwartz B, Simantov R, Kelley S. Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov. 2006;5(10):835–844.
   PubMed Web of Science ®Google Scholar
• Roskoski R. Sunitinib: a VEGF and PDGF receptor protein kinase and angiogenesis inhibitor. Biochem Biophys Res Commun. 2007;356(2):323–328.
   PubMed Web of Science ®Google Scholar
• Zhu C, Ma X, Hu Y, Guo L, Chen B, Shen K, Xiao Y. Safety and efficacy profile of lenvatinib in cancer therapy: a systematic review and meta-analysis. Oncotarget. 2016;7(28):44545–44557.
   PubMedGoogle Scholar
• Abdelaziz A, Vaishampayan U. Cabozantinib for the treatment of kidney cancer. Expert Rev Anticancer Ther. 2017;17(7):577–584.
   PubMed Web of Science ®Google Scholar
• Richeldi L, Cottin V, Flaherty KR, Kolb M, Inoue Y, Raghu G, Taniguchi H, Hansell DM, Nicholson AG, Le Maulf F, et al. Design of the INPULSIS™ trials: two phase 3 trials of nintedanib in patients with idiopathic pulmonary fibrosis. Respir Med. 2014;108(7):1023–1030.
   PubMed Web of Science ®Google Scholar
• Tan E-H, Goss GD, Salgia R, Besse B, Gandara DR, Hanna NH, Yang JCH, Thertulien R, Wertheim M, Mazieres J, et al. Phase 2 trial of linifanib (ABT-869) in patients with advanced non-small cell lung cancer. J Thorac Oncol. 2011;6(8):1418–1425.
   PubMed Web of Science ®Google Scholar
• Meltzer-Mats E, Babai-Shani G, Pasternak L, Uritsky N, Getter T, Viskind O, Eckel J, Cerasi E, Senderowitz H, Sasson S, et al. Synthesis and mechanism of hypoglycemic activity of benzothiazole derivatives. J Med Chem. 2013;56(13):5335–5350.
   PubMed Web of Science ®Google Scholar
• Liu Y, Wang Y, Dong G, Zhang Y, Wu S, Miao Z, Yao J, Zhang W, Sheng C. Novel benzothiazole derivatives with a broad antifungal spectrum: design, synthesis and structure–activity relationships. Med Chem Comm. 2013;4:1551–1561.
   Web of Science ®Google Scholar
• Singh M, Singh SK, Gangwar M, Nath G, Singh SK. Design, synthesis and mode of action of some benzothiazole derivatives bearing an amide moiety as antibacterial agents. RSC Adv. 2014;4:19013–19023.
   Web of Science ®Google Scholar
• Mahesh G, Kumar KA, Reddanna P. Overview on the discovery and development of anti-inflammatory drugs: should the focus be on synthesis or degradation of PGE2? J Inflamm Res. 2021;14:253–263.
   PubMed Web of Science ®Google Scholar
• Siddiqui N, Pandeya SN, Khan SA, Stables J, Rana A, Alam M, Arshad MF, Bhat MA. Synthesis and anticonvulsant activity of sulfonamide derivatives-hydrophobic domain. Bioorg Med Chem Lett. 2007;17(1):255–259.
   PubMed Web of Science ®Google Scholar
• Rana A, Siddiqui N, Khan S. Benzothiazoles: a new profile of biological activities. Indian J Pharm Sci. 2007;69:10.
   Google Scholar
• Shi D-F, Bradshaw TD, Wrigley S, McCall CJ, Lelieveld P, Fichtner I, Stevens MF. Antitumor benzothiazoles. 3. Synthesis of 2-(4-aminophenyl) benzothiazoles and evaluation of their activities against breast cancer cell lines in vitro and in vivo. J Med Chem. 1996;39(17):3375–3384.
   PubMed Web of Science ®Google Scholar
• Hutchinson I, Chua M-S, Browne HL, Trapani V, Bradshaw TD, Westwell AD, Stevens MF. Antitumor benzothiazoles. 14. Synthesis and in vitro biological properties of fluorinated 2-(4-aminophenyl) benzothiazoles. J Med Chem. 2001;44(9):1446–1455.
   PubMed Web of Science ®Google Scholar
• Kok SHL, Gambari R, Chui CH, Yuen MCW, Lin E, Wong RSM, Lau FY, Cheng GYM, Lam WS, Chan SH, et al. Synthesis and anti-cancer activity of benzothiazole containing phthalimide on human carcinoma cell lines. Bioorg Med Chem. 2008;16(7):3626–3631.
   PubMed Web of Science ®Google Scholar
• Shi X-H, Wang Z, Xia Y, Ye T-H, Deng M, Xu Y-Z, Wei Y-Q, Yu L-T. Synthesis and biological evaluation of novel benzothiazole-2-thiol derivatives as potential anticancer agents. Molecules. 2012;17(4):3933–3944.
   PubMed Web of Science ®Google Scholar
• Leong CO, Suggitt M, Swaine DJ, Bibby MC, Stevens MF, Bradshaw TD. In vitro, in vivo, and in silico analyses of the antitumor activity of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazoles. Mol Cancer Ther. 2004;3(12):1565–1575.
   PubMed Web of Science ®Google Scholar
• Mortimer CG, Wells G, Crochard J-P, Stone EL, Bradshaw TD, Stevens MF, Westwell AD. Antitumor benzothiazoles. 26. 2-(3, 4-Dimethoxyphenyl)-5-fluorobenzothiazole (GW 610, NSC 721648), a simple fluorinated 2-arylbenzothiazole, shows potent and selective inhibitory activity against lung, colon, and breast cancer cell lines. J Med Chem. 2006;49(1):179–185.
   PubMed Web of Science ®Google Scholar
• Baffy G. Editorial: hepatocellular carcinoma in type 2 diabetes: more than meets the eye. Off J Am Coll Gastroenterol ACG. 2012;107:53–55.
   PubMed Web of Science ®Google Scholar
• Turan-Zitouni G, Özkay Y, Özdemir A, Asim Kaplancıklı Z, Dilek Altıntop M. Synthesis of some benzothiazole based piperazine-dithiocarbamate derivatives and evaluation of their anticancer activities. Lett Drug Des Discov. 2011;8:830–837.
   Web of Science ®Google Scholar
• Altintop MD, Sever B, Özdemir A, Ilgın S, Atlı Ö, Turan-Zitouni G, Kaplancıklı ZA. Synthesis and evaluation of a series of 1, 3, 4-thiadiazole derivatives as potential anticancer agents. Anticancer Agents Med Chem. 2018;18(11):1606–1616.
   PubMed Web of Science ®Google Scholar
• Tariq S, Kamboj P, Amir M. Therapeutic advancement of benzothiazole derivatives in the last decennial period. Arch Pharm. 2019;352:1800170.
   PubMed Web of Science ®Google Scholar
• Irfan A, Batool F, Zahra Naqvi SA, Islam A, Osman SM, Nocentini A, Alissa SA, Supuran CT. Benzothiazole derivatives as anticancer agents. J Enzyme Inhib Med Chem. 2020;35(1):265–279.
   PubMed Web of Science ®Google Scholar
• Pathak N, Rathi E, Kumar N, Kini SG, Rao CM. A review on anticancer potentials of benzothiazole derivatives. Mini Rev Med Chem. 2020;20(1):12–23.
   PubMed Web of Science ®Google Scholar
• Sever B, Altıntop MD, Özdemir A, Akalın Çiftçi G, Ellakwa DE, Tateishi H, Radwan MO, Ibrahim MAA, Otsuka M, Fujita M, et al. In vitro and in silico evaluation of anticancer activity of new indole-based 1,3,4-oxadiazoles as EGFR and COX-2 inhibitors. Molecules. 2020;25:5190.
   PubMed Web of Science ®Google Scholar
• Haider K, Shrivastava N, Pathak A, Prasad Dewangan R, Yahya S. Shahar Yar, M. Recent advances and SAR study of 2-substituted benzothiazole scaffold based potent chemotherapeutic agents. Results Chem. 2022;4:100258.
   Google Scholar
• Dhadda S, Raigar AK, Saini K, Manju, Guleria A. Benzothiazoles: from recent advances in green synthesis to anti-cancer potential. Sustain Chem Pharm. 2021;24:100521.
   Web of Science ®Google Scholar
• El-Helby A-GA, Sakr H, Eissa IH, Al-Karmalawy AA, El-Adl K. Benzoxazole/benzothiazole-derived VEGFR-2 inhibitors: design, synthesis, molecular docking, and anticancer evaluations. Arch Pharm. 2019;352:1900178.
   Web of Science ®Google Scholar
• Racané L, Ptiček L, Fajdetić G, Tralić-Kulenović V, Klobučar M, Kraljević Pavelić S, Perić M, Paljetak HČ, Verbanac D, Starčević K. Green synthesis and biological evaluation of 6-substituted-2-(2-hydroxy/methoxy phenyl)benzothiazole derivatives as potential antioxidant, antibacterial and antitumor agents. Bioorg Chem. 2020;95:103537.
   PubMed Web of Science ®Google Scholar
• Ammazzalorso A, Carradori S, Amoroso R, Fernández IF. 2-substituted benzothiazoles as antiproliferative agents: novel insights on structure-activity relationships. Eur J Med Chem. 2020;207:112762.
   PubMed Web of Science ®Google Scholar
• Reddy VG, Reddy TS, Jadala C, Reddy MS, Sultana F, Akunuri R, Bhargava SK, Wlodkowic D, Srihari P, Kamal A. Pyrazolo-benzothiazole hybrids: synthesis, anticancer properties and evaluation of antiangiogenic activity using in vitro VEGFR-2 kinase and in vivo transgenic zebrafish model. Eur J Med Chem. 2019;182:111609.
   PubMed Web of Science ®Google Scholar
• Marzouk AA, Abdel-Aziz SA, Abdelrahman KS, Wanas AS, Gouda AM, Youssif BGM, Abdel-Aziz M. Design and synthesis of new 1,6-dihydropyrimidin-2-thio derivatives targeting VEGFR-2: Molecular docking and antiproliferative evaluation. Bioorg Chem. 2020;102:104090.
   PubMed Web of Science ®Google Scholar
• Faraji A, Motahari R, Hasanvand Z, Oghabi Bakhshaiesh T, Toolabi M, Moghimi S, Firoozpour L, Boshagh MA, Rahmani R, Ketabforoosh SHME, et al. Quinazolin-4(3H)-one based agents bearing thiadiazole-urea: synthesis and evaluation of anti-proliferative and antiangiogenic activity. Bioorg Chem. 2021;108:104553.
   PubMed Web of Science ®Google Scholar
• El-Shafey HW, Gomaa RM, El-Messery SM, Goda FE. Synthetic approaches, anticancer potential, HSP90 inhibition, multitarget evaluation, molecular modeling and apoptosis mechanistic study of thioquinazolinone skeleton: promising antibreast cancer agent. Bioorg Chem. 2020;101:103987.
   PubMed Web of Science ®Google Scholar
• Yang S-K, Kang JS, Oelschlaeger P, Yang K-W. Azolylthioacetamide: a highly promising scaffold for the development of metallo-β-lactamase inhibitors. ACS Med Chem Lett. 2015;6(4):455–460.
   PubMed Web of Science ®Google Scholar
• Tilekar K, Upadhyay N, Schweipert M, Hess JD, Macias LH, Mrowka P, Meyer-Almes F-J, Aguilera RJ, Iancu CV, Choe J-Y, et al. Permuted 2, 4-thiazolidinedione (TZD) analogs as GLUT inhibitors and their in-vitro evaluation in leukemic cells. Eur J Pharm Sci. 2020;154:105512.
   PubMed Web of Science ®Google Scholar
• Al-Wahaibi LH, Chakraborty K, Al-Shaalan NH, Majeed MYAS, Blacque O, Al-Mutairi AA, El-Emam AA, Percino MJ, Thamotharan S. Quantitative analysis of hydrogen and chalcogen bonds in two pyrimidine-5-carbonitrile derivatives, potential DHFR inhibitors: an integrated crystallographic and theoretical study. RSC Adv. 2020;10(60):36806–36817.
   PubMed Web of Science ®Google Scholar
• Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1-2):55–63.
   PubMed Web of Science ®Google Scholar
• 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;89:271–277.
   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;107:165–179.
   PubMed Web of Science ®Google Scholar
• Thornton TM, Rincon M. Non-classical p38 map kinase functions: cell cycle checkpoints and survival. Int J Biol Sci. 2009;5(1):44–51.
   PubMed Web of Science ®Google Scholar
• Kumar CP, Reddy TS, Mainkar PS, Bansal V, Shukla R, Chandrasekhar S, Hügel HM. Synthesis and biological evaluation of 5, 10-dihydro-11H-dibenzo [b, e][1, 4] diazepin-11-one structural derivatives as anti-cancer and apoptosis inducing agents. Eur J Med Chem. 2016;108:674–686.
   PubMed Web of Science ®Google Scholar
• ChemOffice. Version 12.0. Cambridge (MA): C.J.C. Cambridge Scientific Computing Inc.
   Google Scholar
• C.C.G.C. Inc. Molecular operating environment (MOE). Montreal: C.C.G.C. Inc; 2016.
   Google Scholar
• Böhm H-J. Prediction of binding constants of protein ligands: a fast method for the prioritization of hits obtained from de novo design or 3D database search programs. J Comput Aided Mol Des. 1998;12(4):309–323.
   PubMed Web of Science ®Google Scholar
• Kramer B, Rarey M, Lengauer T. Evaluation of the FLEXX incremental construction algorithm for protein–ligand docking. Proteins Struct Funct Genet. 1999;37:228–241.
   PubMed Web of Science ®Google Scholar
• Elimam DM, Elgazar AA, El-Senduny FF, El-Domany RA, Badria FA, Eldehna WM. Natural inspired piperine-based ureas and amides as novel antitumor agents towards breast cancer. J Enzyme Inhib Med Chem. 2022;37(1):39–50.
   PubMed Web of Science ®Google Scholar
• Studio, D.J.A.I.S.D., CA, USA. Version 2.5. 2009.
   Google Scholar
• PreADMET. Prediction of ADM/Tox; 2022; [accessed 2022 June 21]. https://preadmet.bmdrc.kr/.
   Google Scholar
• Hamdi A, El-Shafey HW, Othman DIA, El-Azab AS, AlSaif NA, Abdel-Aziz AAM. Design, synthesis, antitumor, and VEGFR-2 inhibition activities of novel 4-anilino-2-vinyl-quinazolines: molecular modeling studies. Bioorg Chem. 2022;122:105710.
   PubMed Web of Science ®Google Scholar
• Hamdi A, Elhusseiny WM, Othman DI, Haikal A, Bakheit AH, El-Azab AS, Al-Agamy MH, Alaa A-M. Synthesis, antitumor, and apoptosis-inducing activities of novel 5-arylidenethiazolidine-2, 4-dione derivatives: histone deacetylases inhibitory activity and molecular docking study. Eur J Med Chem. 2022;244:114827.
   PubMed Web of Science ®Google Scholar
• Selim NM, Elgazar AA, Abdel-Hamid NM, Abu El-Magd MR, Yasri A, El Hefnawy HM, Sobeh MJA. Chrysophanol, physcion, hesperidin and curcumin modulate the gene expression of pro-inflammatory mediators induced by LPS in HepG2: in silico and molecular studies. Antioxidants 2019;8:371.
   Google Scholar
• Elsbaey M, Ibrahim MAA, Bar FA, Elgazar AA. Chemical constituents from coconut waste and their in silico evaluation as potential antiviral agents against SARS-CoV-2. S Afr J Bot. 2021;141:278–289.
   PubMed Web of Science ®Google Scholar
• Elgazar AA, Selim NM, Abdel-Hamid NM, El-Magd MA, El Hefnawy HM. Isolates from Alpinia officinarum Hance attenuate LPS-induced inflammation in HepG2: evidence from in silico and in vitro studies. Phytother Res. 2018;32(7):1273–1288.
   PubMed Web of Science ®Google Scholar
• Elgazar AA, Knany HR, Ali MS. Insights on the molecular mechanism of anti-inflammatory effect of formula from Islamic traditional medicine: an in-silico study. J Tradit Complement Med. 2019;9(4):353–363.
   PubMedGoogle Scholar
• Badria FA, Elgazar AA. Chapter 37 - revealing the molecular mechanism of Olea europaea L. in treatment of cataract. In: Preedy VR, Watson RR, editors. Olives and olive oil in health and disease prevention. 2nd ed. San Diego (CA): Academic Press; 2021. p. 445–456.
   Google Scholar
• Othman DI, Hamdi A, Abdel-Aziz MM, Elfeky SM. Novel 2-arylthiazolidin-4-one-thiazole hybrids with potent activity against Mycobacterium tuberculosis. Bioorg Chem. 2022;124:105809.
   PubMed Web of Science ®Google Scholar
• El-Shafey HW, Gomaa RM, El-Messery SM, Goda FE. Quinazoline based HSP90 inhibitors: synthesis, modeling study and ADME calculations towards breast cancer targeting. Bioorg Med Chem Lett. 2020;30(15):127281.
   PubMed Web of Science ®Google Scholar
• Wadapurkar RM, Shilpa MD, Katti AKS, Sulochana MB. In silico drug design for Staphylococcus aureus and development of host-pathogen interaction network. Inform Med Unlocked. 2018;10:58–70.
   Google Scholar