Design, synthesis and apoptosis inducing effect of novel (Z)-3-(3′-methoxy-4′-(2-amino-2-oxoethoxy)-benzylidene)indolin-2-ones as potential antitumour agents

European Journal of Medicinal Chemistry

Volumn 118, Issue , 2016, Pages 34-46

  Senwar, Kishna Ram ^a   Reddy, T Srinivasa ^a   Thummuri, Dinesh ^a   Sharma, Pankaj ^a   Naidu, V G M ^a   Srinivasulu, Gannoju ^a   Shankaraiah, Nagula ^a  

^a NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH NIPER   (India)

Author keywords

Anticancer; Apoptosis; Benzylideneindolin 2 one; Heterocycles; Knoevenagel condensation; Oxindole

Indexed keywords

3 [3' METHOXY 4' (2 AMINO 2 OXOETHOXY) BENZYLIDENE]INDOLIN 2 ONE; 3 [3' METHOXY 4' (2 MORPHOLINO 2 OXOETHOXY)BENZYLIDENE] 5 METHYLINDOLIN 2 ONE; 3 [3' METHOXY 4' (2 MORPHOLINO 2 OXOETHOXY)BENZYLIDENE]INDOLIN 2 ONE; 3 [3' METHOXY 4' [2 OXO 2 (PIPERIDIN 1 YL)ETHOXY]BENZYLIDENE] 5 METHYLINDOLIN 2 ONE; 3 [3' METHOXY 4' [2 OXO 2 (PIPERIDIN 1 YL)ETHOXY]BENZYLIDENE]INDOLIN 2 ONE; 3 [3' METHOXY 4' [2 OXO 2 (PYRROLIDIN 1 YL)ETHOXY]BENZYLIDENE] 5 METHYLINDOLIN 2 ONE; 3 [3' METHOXY 4' [2 OXO 2 (PYRROLIDIN 1 YL)ETHOXY]BENZYLIDENE]INDOLIN 2 ONE; 3 [4' [2 (2,6 DIMETHYLMORPHOLINO) 2 OXOETHOXY] 3' METHOXYBENZYLIDENE] 5 FLUOROINDOLIN 2 ONE; 3 [4' [2 (2,6 DIMETHYLMORPHOLINO) 2 OXOETHOXY] 3' METHOXYBENZYLIDENE] 5 METHYLINDOLIN 2 ONE; 3 [4' [2 (2,6 DIMETHYLMORPHOLINO) 2 OXOETHOXY] 3' METHOXYBENZYLIDENE]INDOLIN 2 ONE; 3 [4' [2 (INDOLIN 1 YL) 2 OXOETHOXY] 3' METHOXYBENZYLIDENE] 5 METHYLINDOLIN 2 ONE; 3 [4' [2 (INDOLIN 1 YL) 2 OXOETHOXY] 30 METHOXYBENZYLIDENE]INDOLIN 2 ONE; 5 BROMO 3 [3' METHOXY 4' (2 MORPHOLINO 2 OXOETHOXY) BENZYLIDENE]INDOLIN 2 ONE; 5 BROMO 3 [3' METHOXY 4' [2 OXO 2 (PIPERIDIN 1 YL)ETHOXY]BENZYLIDENE]INDOLIN 2 ONE; 5 BROMO 3 [3' METHOXY 4' [2 OXO 2 (PYRROLIDIN 1 YL)ETHOXY]BENZYLIDENE]INDOLIN 2 ONE; 5 BROMO 3 [4' [2 (2,6 DIMETHYLMORPHOLINO) 2 OXOETHOXY] 3' METHOXYBENZYLIDENE]INDOLIN 2 ONE; 5 CHLORO 3 ['3' METHOXY 4' (2 MORPHOLINO 2 OXOETHOXY)BENZYLIDENE]INDOLIN 2 ONE; 5 CHLORO 3 [3' METHOXY 4' [2 OXO 2 (PIPERIDIN 1 YL)ETHOXY]BENZYLIDENE]INDOLIN 2 ONE; 5 CHLORO 3 [3' METHOXY 4' [2 OXO 2 (PYRROLIDIN 1 YL)ETHOXY]BENZYLIDENE]INDOLIN 2 ONE; 5 CHLORO 3 [4' [2 (2,6 DIMETHYLMORPHOLINO) 2 OXOETHOXY] 3' METHOXYBENZYLIDENE]INDOLIN 2 ONE; 5 FLUORO 3 [3' METHOXY 4' (2 MORPHOLINO 2 OXOETHOXY)BENZYLIDENE]INDOLIN 2 ONE; 5 FLUORO 3 [3' METHOXY 4' [2 OXO 2 (PIPERIDIN 1 YL)ETHOXY]BENZYLIDENE]INDOLIN 2 ONE; 5 FLUORO 3 [3' METHOXY 4' [2 OXO 2 (PYRROLIDIN 1 YL)ETHOXY]BENZYLIDENE]INDOLIN 2 ONE; ANTINEOPLASTIC AGENT; CASPASE 3; PROTEIN BAX; PROTEIN BCL 2; SUNITINIB; UNCLASSIFIED DRUG; ACTIN; INDOLE DERIVATIVE; INDOLIN-2-ONE;

ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; CANCER INHIBITION; CARBON NUCLEAR MAGNETIC RESONANCE; CELL CYCLE G0 PHASE; CELL CYCLE G1 PHASE; CELL MIGRATION; CELL PROLIFERATION; COMPARATIVE STUDY; CONFOCAL MICROSCOPY; CONTROLLED STUDY; DRUG DESIGN; DRUG SYNTHESIS; G2 PHASE CELL CYCLE CHECKPOINT; HETERONUCLEAR MULTIPLE BOND CORRELATION; HETERONUCLEAR SINGLE QUANTUM COHERENCE; HUMAN; HUMAN CELL; IC50; IN VITRO STUDY; ISOMER; MALE; MITOCHONDRIAL MEMBRANE POTENTIAL; PHASE CONTRAST MICROSCOPY; PROSTATE CANCER CELL LINE; PROSTATE EPITHELIUM CELL; PROTEIN EXPRESSION; PROTON NUCLEAR MAGNETIC RESONANCE; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION; THIN LAYER CHROMATOGRAPHY; TUMOR GROWTH; CELL CYCLE; CELL MOTION; CHEMISTRY; DRUG EFFECTS; METABOLISM; PATHOLOGY; PROSTATE TUMOR; SYNTHESIS; TUMOR CELL LINE;

ACTINS; ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL CYCLE; CELL LINE, TUMOR; CELL MOVEMENT; CELL PROLIFERATION; CHEMISTRY TECHNIQUES, SYNTHETIC; DRUG DESIGN; HUMANS; INDOLES; MALE; PROSTATIC NEOPLASMS;

EID: 84964461716     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2016.04.025     Document Type: Article

References (47)

1. R.L. Siegel, K.D. Miller, A. Jemal, Cancer statistics, 2015, CA Cancer J. Clin. 65 (2015) 5-29.
2. A. Millemaggi, R.J.K. Taylor, 3-Alkenyl-oxindoles: natural products, pharmaceuticals, and recent synthetic advances in tandem/telescoped approaches, Eur. J. Org. Chem. 24 (2010) 4527-4547.
3. S. Peddibhotla, 3-Substituted-3-hydroxy-2-oxindole, an emerging new scaffold for drug discovery with potential anti-cancer and other biological activities, Curr. Bioact. Compd. 5 (2009) 20-38.
4. G.S. Singh, Z.Y. Desta, Isatins as privileged molecules in design and synthesis of spiro-fused cyclic frameworks, Chem. Rev. 112 (2012) 6104-6155.
5. C.V. Galliford, K.A. Scheidt, Pyrrolidinyl-spirooxindole natural products as inspirations for the development of potential therapeutic agents, Angew. Chem. Int. Ed. 46 (2007) 8748-8758.
6. G.H. Zheng, J.J. Shen, Y.C. Zhan, H. Yi, S.T. Xue, Z. Wang, X.Y. Ji, Z.R. Li, Design, synthesis and in vitro and in vivo antitumour activity of 3-benzylideneindolin- 2-one derivatives, a novel class of small-molecule inhibitors of the MDM2ep53 interaction, Eur. J. Med. Chem. 81 (2014) 277-288.
7. G. Bhaskar, Y. Arun, C. Balachandran, C. Saikumar, P.T. Perumal, Synthesis of novel spirooxindole derivatives by one pot multicomponent reaction and their antimicrobial activity, Eur. J. Med. Chem. 51 (2012) 79-91.
8. Y. Kia, H. Osman, R.S. Kumar, V. Murugaiyah, A. Basiri, S. Perumal, H.A. Wahab, C.S. Bing, Synthesis and discovery of novel piperidone-grafted mono- and bisspirooxindole-hexahydropyrrolizines as potent cholinesterase inhibitors, Biorg. Med. Chem. 21 (2013) 1696-1707.
9. +-dependent histone deacetylases (sirtuins), J. Med. Chem. 53 (2009) 1383-1386.
10. A. Leoni, A. Locatelli, R. Morigi, M. Rambaldi, 2-Indolinone a versatile scaffold for treatment of cancer: a patent review (2008-2014), Expert Opin. Ther. Pat. 26 (2016) 149-173.
11. C.R. Prakash, S. Raja, Indolinones as promising scaffold as kinase inhibitors: a review, Mini. Rev. Med. Chem. 12 (2012) 98-119.
12. G.J. Roth, R. Binder, F. Colbatzky, C. Dallinger, R. Schlenker-Herceg, F. Hilberg, S.L. Wollin, R. Kaiser, Nintedanib: from discovery to the clinic, J. Med. Chem. 58 (2015) 1053-1063.
13. R.J. Motzer, M.D. Michaelson, B.G. Redman, G.R. Hudes, G. Wilding, R.A. Figlin, M.S. Ginsberg, S.T. Kim, C.M. Baum, S.E. De Primo, J.Z. Li, C.L. Bello, C.P. Theuer, D.J. George, B.I. Rini, Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma, J. Clin. Oncol. 24 (2006) 16-24.
14. H. Prenen, J. Cools, N. Mentens, C. Folens, R. Sciot, P. Schöffski, A.V. Oosterom, P. Marynen, M. Debiec-Rychter, Efficacy of the kinase inhibitor SU11248 against gastrointestinal stromal tumor mutants refractory to imatinib mesylate, Clin. Cancer Res. 12 (2006) 2622-2627.
15. J.J. Cui, M. McTigue, M. Nambu, M. Tran-Dube, M. Pairish, H. Shen, L. Jia, H. Cheng, J. Hoffman, P. Le, M. Jalaie, G.H. Goetz, K. Ryan, N. Grodsky, Y.L. Deng, M. Parker, S. Timofeevski, B.W. Murray, S. Yamazaki, S. Aguirre, Q. Li, H. Zou, J. Christensen, Discovery of a novel class of exquisitely selective mesenchymal epithelial transition factor (MET) protein kinase inhibitors and identification of the clinical candidate 2-(4-(1-(quinolin-6-ylmethyl)-1H- [1,2,3]triazolo[4,5-b]pyrazin-6-yl)-1H-pyrazol-1-yl)ethanol (PF-04217903) for the treatment of cancer, J. Med. Chem. 55 (2012) 8091-8109.
16. M. Haddach, J. Michaux, M.K. Schwaebe, F. Pierre, S.E. O'Brien, C. Borsan, J. Tran, N. Raffaele, S. Ravula, D. Drygin, A. Siddiqui-Jain, L. Darjania, R. Stansfield, C. Proffitt, D. Macalino, N. Streiner, J. Bliesath, M. Omori, J.P. Whitten, K. Anderes, W.G. Rice, D.M. Ryckman, Discovery of CX-6258. A potent, selective, and orally efficacious pan-Pim kinases inhibitor, ACS Med. Chem. Lett. 3 (2012) 135-139.
17. T.P. Cho, S.Y. Dong, F. Jun, F.J. Hong, Y.J. Liang, X. Lu, P.J. Hua, L.Y. Li, Z. Lei, H. Bing, Z. Ying, L.F. Qiong, F.B. Bei, L.L. Guang, G.A. Shen, S.G. Hong, S.W. Hong, M.X. Tai, Novel potent orally active multitargeted receptor tyrosine kinase inhibitors: synthesis, structure-activity relationships, and antitumor activities of 2-indolinone derivatives, J. Med. Chem. 53 (2010) 8140-8149.
18. A.D. Jagtap, P.T. Chang, J.R. Liu, H.C. Wang, N.B. Kondekar, L.J. Shen, H.W. Tseng, G.S. Chen, J.W. Chern, Novel acylureidoindolin-2-one derivatives as dual Aurora B/FLT3 inhibitors for the treatment of acute myeloid leukemia, Eur. J. Med. Chem. 85 (2014) 268-288.
19. H.C. Wang, A.D. Jagtap, P.T. Chang, J.R. Liu, C.P. Liu, H.W. Tseng, G.S. Chen, J.W. Chern, Bioisosteric replacement of an acylureido moiety attached to an indolin-2-one scaffold with a malonamido or a 2/4-pyridinoylamido moiety produces a selectively potent Aurora-B inhibitor, Eur. J. Med. Chem. 84 (2014) 312-334.
20. C. Pergola, N. Gaboriaud-Kolar, N. Jestädt, S. König, M. Kritsanida, A.M. Schaible, H. Li, U. Garscha, C. Weinigel, D. Barz, K.F. Albring, O. Huber, A.L. Skaltsounis, O. Werz, Indirubin core structure of glycogen synthase kinase-3 inhibitors as novel chemotype for intervention with 5-lipoxygenase, J. Med. Chem. 57 (2014) 3715-3723.
21. H.N. Bramson, J. Corona, S.T. Davis, S.H. Dickerson, M. Edelstein, S.V. Frye, R.T. Gampe Jr., P.A. Harris, A. Hassell, W.D. Holmes, R.N. Hunter, K.E. Lackey, B. Lovejoy, M.J. Luzzio, V. Montana, W.J. Rocque, D. Rusnak, L. Shewchuk, J.M. Veal, D.H. Walker, L.F. Kuyper, Oxindole-based inhibitors of cyclindependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and xray crystallographic analysis, J. Med. Chem. 44 (2001) 4339-4358.
22. P.B. Sampson, Y. Liu, B. Forrest, G. Cumming, S.W. Li, N.K. Patel, L. Edwards, R. Laufer, M. Feher, F. Ban, D.E. Awrey, G. Mao, O. Plotnikova, R. Hodgson, I. Beletskaya, J.M. Mason, X. Luo, V. Nadeem, X. Wei, R. Kiarash, B. Madeira, P. Huang, T.W. Mak, G. Pan, H.W. Pauls, The Discovery of Polo-like kinase 4 inhibitors: design and optimization of spiro[cyclopropane-1,3′[3H]indol]- 2′(1′H)-ones as orally bioavailable antitumor Agents, J. Med. Chem. 58 (2015) 147-169.
23. K.R. Senwar, P. Sharma, T.S. Reddy, M.K. Jeengar, V.L. Nayak, V.G.M. Naidu, A. Kamal, N. Shankaraiah, Spirooxindole-derived morpholine-fused-1,2,3-triazoles: design, synthesis, cytotoxicity and apoptosis inducing studies, Eur. J. Med. Chem. 102 (2015) 413-424.
24. K.R. Senwar, P. Sharma, S. Nekkanti, M. Sathish, A. Kamal, B. Sridhar, N. Shankaraiah, A one-pot 'click'reaction from spiro-epoxides catalyzed by Cu (i)-pyrrolidinyl-oxazole-carboxamide, New J. Chem. 39 (2015) 3973-3981.
25. M. Chouhan, K.R. Senwar, R. Sharma, V. Grover, V.A. Nair, Regiospecific epoxide opening: a facile approach for the synthesis of 3-hydroxy-3-aminomethylindolin-2-one derivatives, Green Chem. 13 (2011) 2553-2560.
26. M. Chouhan, K.R. Senwar, K. Kumar, R. Sharma, V.A. Nair, Catalytic CeH activation of arylacetylenes: a fast assembly of 3-(arylethynyl)-3-hydroxyindolin-2-ones using CuI/DBU, Synthesis 46 (2014) 195-202.
27. 2O-mediated isatin spiro-epoxide ring opening with NaCN: synthesis of novel 3-tetrazolylmethyl-3-hydroxy-oxindole hybrids and their anticancer evaluation, Eur. J. Med. Chem. 104 (2015) 11-24.
28. R.D. Taylor, M. MacCoss, A.D.G. Lawson, Rings in drugs, J. Med. Chem. 57 (2014) 5845-5859.
29. M. Andrs, J. Korabecny, D. Jun, Z. Hodny, J. Bartek, K. Kuca, Phosphatidylinositol 3-kinase (PI3K) and phosphatidylinositol 3-kinase-related kinase (PIKK) inhibitors: importance of the morpholine ring, J. Med. Chem. 58 (2014) 41-71.
30. L. Sun, N. Tran, F. Tang, H. App, P. Hirth, G. McMahon, C. Tang, Synthesis and biological evaluations of 3-substituted indolin-2-ones: a novel class of tyrosine kinase inhibitors that exhibit selectivity toward particular receptor tyrosine kinases, J. Med. Chem. 41 (1998) 2588-2603.
31. X. Chen, T. Yang, A. Deivasigamani, M.K. Shanmugam, K.M. Hui, G. Sethi, M.L. Go, N0-Alkylaminosulfonyl analogues of 6-fluorobenzylideneindolinones with desirable physicochemical profiles and potent growth inhibitory activities on hepatocellular carcinoma, Chem Med Chem 10 (2015) 1548-1558.
32. M. Nishikawa, H. Miyake, M. Fujisawa, Enhanced sensitivity to sunitinib by inhibition of Akt1 expression in human castration-resistant prostate cancer PC3 cells both in vitro and in vivo, Urology 85 (2015) 1215.e1-1215.e7.
33. F. Yang, V. Jove, H. Xin, M. Hedvat, T.E. Van Meter, H. Yu, Sunitinib induces apoptosis and growth arrest of medulloblastoma tumor cells by inhibiting STAT3 and AKT signaling pathways, Mol. Cancer Res. 8 (2010) 35-45.
34. E. Chinchar, K.L. Makey, J. Gibson, F. Chen, S.A. Cole, G.C. Megason, S. Vijayakumar, L. Miele, J.W. Gu, Sunitinib significantly suppresses the proliferation, migration, apoptosis resistance, tumor angiogenesis and growth of triple-negative breast cancers but increases breast cancer stem cells, Vasc. Cell. 6 (2014) 12.
35. O. Belali, M. Ansari, H. Korashy, Sunitinib induces growth inhibition and apoptosis in breast cancer MDA-MB-231 cells through FOXO3a signaling pathway, FASEB J. 29 (Suppl. 1) (2015) 619-623.
36. T.S. Reddy, H. Kulhari, V.G. Reddy, V. Bansal, A. Kamal, R. Shukla, Design, synthesis and biological evaluation of 1, 3-diphenyl-1H-pyrazole derivatives containing benzimidazole skeleton as potential anticancer and apoptosis inducing agents, Eur. J. Med. Chem. 101 (2015) 790-805.
37. M.P. Sheetz, D. Felsenfeld, C.G. Galbraith, D. Choquet, Cell migration as a fivestep cycle, Biochem. Soc. Symp. 65 (1999) 233-243.
38. A. Kamal, T.S. Reddy, S. Polepalli, N. Shalini, V.G. Reddy, A.S. Rao, N. Jain, N. Shankaraiah, Synthesis and biological evaluation of podophyllotoxin congeners as tubulin polymerization inhibitors, Bioorg. Med. Chem. 22 (2014) 5466-5475.
39. D. Hanahan, R.A. Weinberg, Hallmarks of cancer: the next generation, Cell 144 (2011) 646-674.
40. A. Kamal, T.S. Reddy, M.V.P.S. Vishnuvardhan, V.D. Nimbarte, A.V. Subba Rao, V. Srinivasulu, N. Shankaraiah, Synthesis of 2-aryl-1,2,4-oxadiazolo-benzimidazoles: tubulin polymerization inhibitors and apoptosis inducing agents, Bioorg. Med. Chem. 23 (2015) 4608-4623.
41. X.D. Wang, The expanding role of mitochondria in apoptosis, Genes Dev. 15 (2001) 2922-2933.
42. I. Kruman, Q. Guo, M.P. Mattson, Calcium and reactive oxygen species mediate staurosporine-induced mitochondrial dysfunction and apoptosis in PC12 cells, J. Neurosci. Res. 51 (1998) 293-308.
43. C. Praveen Kumar, T.S. Reddy, P.S. Mainkar, V. Bansal, R. Shukla, S. Chandrasekhar, H.M. Hügel, Synthesis and biological evaluation of 5,10-dihydro-11H-dibenzo[b, e][1,4]diazepin-11-one structural derivatives as anticancer and apoptosis inducing agents, Eur. J. Med. Chem. 108 (2016) 674-686.
44. A.G. Porter, R.U. Jänicke, Emerging roles of caspase-3 in apoptosis, Cell Death Differ. 6 (1999) 99-104.
45. S. Shrivastava, P. Kulkarni, D. Thummuri, M.K. Jeengar, V.G.M. Naidu, M. Alvala, G.B. Redddy, S. Ramakrishna, Piperlongumine, an alkaloid causes inhibition of PI3 K/Akt/mTOR signaling axis to induce caspase-dependent apoptosis in human triple-negative breast cancer cells, Apoptosis 19 (2014) 1148-1164.
46. B. Janji, L. Vallar, Z. Al. Tanoury, F. Bernardin, G. Vetter, E. Schaffner-Reckinger, G. Berchem, E. Friederich, S. Chouaib, The actin filament cross-linker L-plastin confers resistance to TNF-alpha in MCF-7 breast cancer cells in a phosphorylation-dependent manner, J. Cell Mol. Med. 14 (2010) 1264-1275.
47. D. Thummuri, M.K. Jeengar, S. Srivastava, A. Areti, V.G. Yerra, S. Yamjala, P. Komirishetty, V.G.M. Naidu, A. Kumar, R. Sistla, Boswellia ovalifoliolata abrogates ROS mediated NF-kB activation, causes apoptosis and chemosensitization in Triple Negative Breast Cancer cells, Environ. Toxicol. Pharmacol. 38 (2014) 58-70.