Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Molecular Docking and In Vitro Anticancer Screening of Synthesized Arylthiazole linked 2H-indol-2-one Derivatives as VEGFR-2 Kinase Inhibitors

Author(s): Nishtha Shalmali, Sandhya Bawa*, Md Rahmat Ali, Sourav Kalra, Raj Kumar, Bushra Zeya, Moshahid Alam Rizvi, Sangh Partap and Asif Husain

Volume 22, Issue 11, 2022

Published on: 20 January, 2022

Page: [2166 - 2180] Pages: 15

DOI: 10.2174/1871520621666211118102139

Price: $65

conference banner
Abstract

Background: Indoline-2,3-dione comprises a leading course group of heterocycles endowed with appealing biological actions, including anticancer activity. There are significant justifications for exploring the anticancer activity of Schiff base derivatives of isatin as a vast number of reports have documented remarkable antiproliferative action of isatin nucleus against various cancer cell lines.

Aims and Objectives: A series of arylthiazole linked 2H-indol-2-one derivatives (5a-t) was designed and synthesized as potential VEGFR-2 kinase inhibitors keeping the essential pharmacophoric features of standard drugs, like sunitinib, sorafenib, nintedanib, etc. They were evaluated for their in vitro anticancer activity. The aim of this study was to investigate and assess the anticancer potential of isatin-containing compounds along with their kinase inhibition activity.

Methods: The title compounds were synthesized by reacting substituted isatins with para-substituted arylthiazoles using appropriate reaction conditions. Selected synthesized derivatives went under preliminary screening against a panel of 60 cancer cell lines at NCI, the USA, for single-dose and five dose assays. Molecular docking was performed to explore the binding and interactions with the active sites of the VEGFR-2 receptor (PDB Id: 3VHE). Derivatives 5a, 5b, 5c, 5d, 5g, 5h, and 5m were assessed for in vitro inhibition potency against Human VEGFR-2 using ELISA (Enzyme- Linked Immunosorbent Assay) kit. All the target compounds were determined against human colon cancer cell line SW480 (colorectal adenocarcinoma cells). Cellular apoptosis/necrosis was determined by flow cytometry using annexin V-FITC. DNA content of the cells was analyzed by flow cytometry and the cycle distribution was quantified.

Results: Compounds 5a and 5g exhibited noteworthy inhibition during a five-dose assay against a panel of 60 cell lines with MID GI50 values of 1.69 and 1.54 μM, respectively. Also, both the lead compounds 5a and 5g demonstrated promising VEGFR-2 inhibitory activity with IC50 values of 5.43±0.95 and 9.63±1.32 μM, respectively. The aforesaid potent compounds were found effective against SW480 (colorectal adenocarcinoma cells) with IC50 values of 31.44 μM and 106.91 μM, respectively. Compound 5a was found to arrest the cell cycle at the G2/M phase, increasing apoptotic cell death. The docking study also supported VEGFR-2 inhibitory activity as both compounds 5a and 5g displayed promising binding and interactions with the active sites of VEGFR-2 receptor (PDB: 3VHE) with docking scores - 9.355 and -7.758, respectively. All the compounds obeyed Lipinski’s rule of five.

Conclusion: Indoline-2,3-dione and thiazole have huge potential to be considered a steer combination approach for developing promising kinase inhibitors as cancer therapeutics.

Keywords: Anticancer, VEGFR-2, isatin, arylthiazole, docking, kinase inhibitors, NCI.

« Previous Next »
Graphical Abstract

[1]
de Martel, C.; Georges, D.; Bray, F.; Ferlay, J.; Clifford, G.M. Global burden of cancer attributable to infections in 2018: A worldwide incidence analysis. Lancet Glob. Health, 2020, 8(2), e180-e190.
[http://dx.doi.org/10.1016/S2214-109X(19)30488-7] [PMID: 31862245]
[2]
Qi, X.X.; Shen, P. Associations of dietary protein intake with all-cause, cardiovascular disease, and cancer mortality: A systematic review and meta-analysis of cohort studies. Nutr. Metab. Cardiovasc. Dis., 2020, 30(7), 1094-1105.
[http://dx.doi.org/10.1016/j.numecd.2020.03.008] [PMID: 32451273]
[3]
Yousef, M.A.; Ali, A.M.; El-Sayed, W.M.; Qayed, W.S.; Farag, H.H.A.; Aboul-Fadl, T. Design and synthesis of novel isatin-based derivatives targeting cell cycle checkpoint pathways as potential anticancer agents. Bioorg. Chem., 2020, 105, 104366.
[http://dx.doi.org/10.1016/j.bioorg.2020.104366] [PMID: 33212312]
[4]
Khajouei, M.R.; Mohammadi-Farani, A.; Moradi, A.; Aliabadi, A. Synthesis and evaluation of anticonvulsant activity of (Z)-4-(2-oxoindolin-3-ylideneamino)-N-phenylbenzamide derivatives in mice. Res. Pharm. Sci., 2018, 13(3), 262-272.
[http://dx.doi.org/10.4103/1735-5362.228956] [PMID: 29853935]
[5]
Xu, Z.; Zhao, S.J.; Lv, Z.S.; Gao, F.; Wang, Y.; Zhang, F.; Bai, L.; Deng, J.L. Fluoroquinolone-isatin hybrids and their biological activities. Eur. J. Med. Chem., 2019, 162, 396-406.
[http://dx.doi.org/10.1016/j.ejmech.2018.11.032] [PMID: 30453247]
[6]
Ramadan, M.A.G.; Baloglu, M.C.; Altunoglu, Y.C.; Kandemirli, F.; Burhan, H.; Aygṻn, A.; Sayiner, H.S.; Ozyigit, F.; Sen, F. Evaluation of biological activity of 5-fluoro-isatin thiosemicarbazone derivatives. J. Nanostruct., 2020, 10(3), 509-517.
[http://dx.doi.org/10.22052/JNS.2020.03.007]
[7]
Altowyan, M.S.; Ali, M.; Soliman, S.M.; Al-Majid, A.M.; Islam, M.S.; Yousuf, S.; Choudhary, M.I.; Ghabbour, H.A.; Barakat, A. Synthesis, computational studies and biological activity of oxamohydrazide derivatives bearing isatin and ferrocene scaffolds. J. Mol. Struct., 2020, 1202, 127372.
[http://dx.doi.org/10.1016/j.molstruc.2019.127372]
[8]
Dar, O.A.; Lone, S.A.; Malik, M.A.; Aqlan, F.M.; Wani, M.Y.; Hashmi, A.A.; Ahmad, A. Synthesis and synergistic studies of isatin based mixed ligand complexes as potential antifungal therapeutic agents. Heliyon, 2019, 5(7), e02055.
[http://dx.doi.org/10.1016/j.heliyon.2019.e02055] [PMID: 31360786]
[9]
Eldehna, W.M.; Altoukhy, A.; Mahrous, H. Abdel-Aziz, H.A. Design, synthesis and QSAR study of certain isatin-pyridine hybrids as potential anti-proliferative agents. Eur. J. Med. Chem., 2015, 90, 684-694.
[http://dx.doi.org/10.1016/j.ejmech.2014.12.010] [PMID: 25499988]
[10]
Sharma, P.; Senwar, K.R.; Jeengar, M.K.; Reddy, T.S.; Naidu, V.G.; Kamal, A.; Shankaraiah, N. H2O-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., 2015, 104, 11-24.
[http://dx.doi.org/10.1016/j.ejmech.2015.09.025] [PMID: 26413726]
[11]
Pervez, H.; Ramzan, M.; Yaqub, M.; Khan, K.M. Synthesis, cytotoxic and phytotoxic effects of some new N4-Aryl substituted Isatin-3-thiosemicarbazones. Lett. Drug Des. Discov., 2011, 8, 452-458.
[http://dx.doi.org/10.2174/157018011795514159]
[12]
Arun, Y.; Bhaskar, G.; Balachandran, C.; Ignacimuthu, S.; Perumal, P.T. Facile one-pot synthesis of novel dispirooxindole-pyrrolidine derivatives and their antimicrobial and anticancer activity against A549 human lung adenocarcinoma cancer cell line. Bioorg. Med. Chem. Lett., 2013, 23(6), 1839-1845.
[http://dx.doi.org/10.1016/j.bmcl.2013.01.023] [PMID: 23395665]
[13]
Havrylyuk, D.; Kovach, N.; Zimenkovsky, B.; Vasylenko, O.; Lesyk, R. Synthesis and anticancer activity of isatin-based pyrazolines and thiazolidines conjugates. Arch. Pharm. (Weinheim), 2011, 344(8), 514-522.
[http://dx.doi.org/10.1002/ardp.201100055] [PMID: 21681810]
[14]
Evdokimov, N.M.; Magedov, I.V.; McBrayer, D.; Kornienko, A. Isatin derivatives with activity against apoptosis-resistant cancer cells. Bioorg. Med. Chem. Lett., 2016, 26(6), 1558-1560.
[http://dx.doi.org/10.1016/j.bmcl.2016.02.015] [PMID: 26883150]
[15]
Karthikeyan, C.; Solomon, V.R.; Lee, H.; Trivedi, P. Design, synthesis and biological evaluation of some isatin-linked chalcones as novel anti-breast cancer agents: a molecular hybridization approach. Biomed. Prev. Nutr., 2013, 3(4), 325-330.
[http://dx.doi.org/10.1016/j.bionut.2013.04.001]
[16]
Rezki, N.; Almehmadi, M.A.; Ihmaid, S.; Shehata, A.M.; Omar, A.M.; Ahmed, H.E.A.; Aouad, M.R. Novel scaffold hopping of potent benzothiazole and isatin analogues linked to 1,2,3-triazole fragment that mimic quinazoline epidermal growth factor receptor inhibitors: Synthesis, antitumor and mechanistic analyses. Bioorg. Chem., 2020, 103, 104133.
[http://dx.doi.org/10.1016/j.bioorg.2020.104133] [PMID: 32745759]
[17]
Aneja, B.; Khan, N.S.; Khan, P.; Queen, A.; Hussain, A.; Rehman, M.T.; Alajmi, M.F.; El-Seedi, H.R.; Ali, S.; Hassan, M.I.; Abid, M. Design and development of Isatin-triazole hydrazones as potential inhibitors of microtubule affinity-regulating kinase 4 for the therapeutic management of cell proliferation and metastasis. Eur. J. Med. Chem., 2019, 163, 840-852.
[http://dx.doi.org/10.1016/j.ejmech.2018.12.026] [PMID: 30579124]
[18]
Teng, Y.O.; Zhao, H.Y.; Wang, J.; Liu, H.; Gao, M.L.; Zhou, Y.; Han, K.L.; Fan, Z.C.; Zhang, Y.M.; Sun, H.; Yu, P. Synthesis and anti-cancer activity evaluation of 5-(2-carboxyethenyl)-isatin derivatives. Eur. J. Med. Chem., 2016, 112, 145-156.
[http://dx.doi.org/10.1016/j.ejmech.2015.12.050] [PMID: 26890120]
[19]
Ali, A.Q.; Teoh, S.G.; Salhin, A.; Eltayeb, N.E.; Ahamed, M.B.K.; Majid, A.M.S.A. Synthesis of platinum(II) complexes of isatinthiosemicarbazones derivatives: in vitro anti-cancer and deoxyribose nucleic acid binding activities. Inorg. Chim. Acta, 2014, 416, 235-244.
[http://dx.doi.org/10.1016/j.ica.2014.03.029]
[20]
Pajouhesh, H.; Parson, R.; Popp, F.D. Potential anticonvulsants VI: condensation of isatins with cyclohexanone and other cyclic ketones. J. Pharm. Sci., 1983, 72(3), 318-321.
[http://dx.doi.org/10.1002/jps.2600720330] [PMID: 6842387]
[21]
Vine, K.L.; Locke, J.M.; Ranson, M.; Benkendorff, K.; Pyne, S.G.; Bremner, J.B. In vitro cytotoxicity evaluation of some substituted isatin derivatives. Bioorg. Med. Chem., 2007, 15(2), 931-938.
[http://dx.doi.org/10.1016/j.bmc.2006.10.035] [PMID: 17088067]
[22]
Vine, K.L.; Locke, J.M.; Ranson, M.; Pyne, S.G.; Bremner, J.B. An investigation into the cytotoxicity and mode of action of some novel N-alkyl-substituted isatins. J. Med. Chem., 2007, 50(21), 5109-5117.
[http://dx.doi.org/10.1021/jm0704189] [PMID: 17887662]
[23]
Matesic, L.; Locke, J.M.; Bremner, J.B.; Pyne, S.G.; Skropeta, D.; Ranson, M.; Vine, K.L. N-phenethyl and N-naphthylmethyl isatins and analogues as in vitro cytotoxic agents. Bioorg. Med. Chem., 2008, 16(6), 3118-3124.
[http://dx.doi.org/10.1016/j.bmc.2007.12.026] [PMID: 18182300]
[24]
Prenen, H.; Cools, J.; Mentens, N.; Folens, C.; Sciot, R.; Schöffski, P.; Van Oosterom, A.; Marynen, P.; Debiec-Rychter, M. Efficacy of the kinase inhibitor SU11248 against gastrointestinal stromal tumor mutants refractory to imatinib mesylate. Clin. Cancer Res., 2006, 12(8), 2622-2627.
[http://dx.doi.org/10.1158/1078-0432.CCR-05-2275] [PMID: 16638875]
[25]
Motzer, R.J.; Michaelson, M.D.; Redman, B.G.; Hudes, G.R.; Wilding, G.; Figlin, R.A.; Ginsberg, M.S.; Kim, S.T.; Baum, C.M.; DePrimo, S.E.; Li, J.Z.; Bello, C.L.; Theuer, C.P.; George, D.J.; Rini, B.I. 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., 2006, 24(1), 16-24.
[http://dx.doi.org/10.1200/JCO.2005.02.2574] [PMID: 16330672]
[26]
Kidwai, M.; Jahan, A.; Mishra, N.K. Isatins: A diversity orientated biological profile. Med. Chem., 2014, 4, 451-468.
[27]
Al-Wabli, R.I.; Zakaria, A.S.; Attia, M.I. Synthesis, spectroscopic characterization and antimicrobial potential of certain new isatin-indole molecular hybrids. Molecules, 2017, 22(11), 1958.
[http://dx.doi.org/10.3390/molecules22111958] [PMID: 29140257]
[28]
Eldehna, W.M.; Al-Ansary, G.H.; Bua, S.; Nocentini, A.; Gratteri, P.; Altoukhy, A.; Ghabbour, H.; Ahmed, H.Y.; Supuran, C.T. Novel indolin-2-one-based sulfonamides as carbonic anhydrase inhibitors: Synthesis, in vitro biological evaluation against carbonic anhydrases isoforms I, II, IV and VII and molecular docking studies. Eur. J. Med. Chem., 2017, 127, 521-530.
[http://dx.doi.org/10.1016/j.ejmech.2017.01.017] [PMID: 28109946]
[29]
Nath, R.; Pathania, S.; Grover, G.; Akhtar, M.J. Isatin containing heterocycles for different biological activities: Analysis of structure activity relationship. J. Mol. Struct., 2020, 1222, 128900.
[http://dx.doi.org/10.1016/j.molstruc.2020.128900]
[30]
Guo, H. Isatin derivatives and their anti-bacterial activities. Eur. J. Med. Chem., 2019, 164, 678-688.
[http://dx.doi.org/10.1016/j.ejmech.2018.12.017] [PMID: 30654239]
[31]
Dhillon, S. Nintedanib: a review of its use as second-line treatment in adults with advanced non-small cell lung cancer of adenocarcinoma histology. Target. Oncol., 2015, 10(2), 303-310.
[http://dx.doi.org/10.1007/s11523-015-0367-8] [PMID: 25894578]
[32]
Rossi, A.; Latiano, T.P.; Parente, P.; Chiarazzo, C.; Limosani, F.; Di Maggio, G.; Maiello, E. The potential role of nintedanib in treating colorectal cancer. Expert Opin. Pharmacother., 2017, 18(11), 1153-1162.
[http://dx.doi.org/10.1080/14656566.2017.1346086] [PMID: 28649871]
[33]
Van Cutsem, E.; Yoshino, T.; Hocke, J.; Oum’Hamed, Z.; Studeny, M.; Tabernero, J. Rationale and design for the LUME-Colon 1 study: A randomized, double-blind, placebo-controlled phase III trial of nintedanib plus best supportive care versus placebo plus best supportive care in patients with advanced colorectal cancer refractory to standard treatment. Clin. Colorectal Cancer, 2016, 15(1), 91-94.e1.
[http://dx.doi.org/10.1016/j.clcc.2015.09.005] [PMID: 26603056]
[34]
Quintela-Fandino, M.; Urruticoechea, A.; Guerra, J.; Gil, M.; Gonzalez-Martin, A.; Marquez, R.; Hernandez-Agudo, E.; Rodriguez-Martin, C.; Gil-Martin, M.; Bratos, R.; Escudero, M.J.; Vlassak, S.; Hilberg, F.; Colomer, R. Phase I clinical trial of nintedanib plus paclitaxel in early HER-2-negative breast cancer (CNIO-BR-01-2010/GEICAM-2010-10 study). Br. J. Cancer, 2014, 111(6), 1060-1064.
[http://dx.doi.org/10.1038/bjc.2014.397] [PMID: 25058346]
[35]
Goodman, V.L.; Rock, E.P.; Dagher, R.; Ramchandani, R.P.; Abraham, S.; Gobburu, J.V.; Booth, B.P.; Verbois, S.L.; Morse, D.E.; Liang, C.Y.; Chidambaram, N.; Jiang, J.X.; Tang, S.; Mahjoob, K.; Justice, R.; Pazdur, R. Approval summary: sunitinib for the treatment of imatinib refractory or intolerant gastrointestinal stromal tumors and advanced renal cell carcinoma. Clin. Cancer Res., 2007, 13(5), 1367-1373.
[http://dx.doi.org/10.1158/1078-0432.CCR-06-2328] [PMID: 17332278]
[36]
Chen, B.; Zhao, R.; Wang, B.; Droghini, R.; Lajeunesse, J.; Sirard, P.; Endo, M.; Balasubramanian, B.; Barrish, J.C. A new and efficient preparation of 2-aminothiazole-5-carbamides: applications to the synthesis of the anti-cancer drug dasatinib. ARKIVOC, 2010, 6, 32-38.
[http://dx.doi.org/10.3998/ark.5550190.0011.604]
[37]
Kantarjian, H.; Jabbour, E.; Grimley, J.; Kirkpatrick, P. Dasatinib. Nat. Rev. Drug Discov., 2006, 5(9), 717-718.
[http://dx.doi.org/10.1038/nrd2135] [PMID: 17001803]
[38]
Miettinen, M.; Rikala, M.S.; Rys, J.; Lasota, J.; Wang, Z.F. Vascular endothelial growth factor receptor 2 as a marker for malignant vascular tumors and mesothelioma: An immunohistochemical study of 262 vascular endothelial and 1640 nonvascular tumors. Am. J. Surg. Pathol., 2012, 36(4), 629-639.
[http://dx.doi.org/10.1097/PAS.0b013e318243555b] [PMID: 22314185]
[39]
Solomon, V.R.; Hu, C.; Lee, H. Hybrid pharmacophore design and synthesis of isatin-benzothiazole analogs for their anti-breast cancer activity. Bioorg. Med. Chem., 2009, 17(21), 7585-7592.
[http://dx.doi.org/10.1016/j.bmc.2009.08.068] [PMID: 19804979]
[40]
Prakash, C.R.; Theivendren, P.; Raja, S. Indolin-2-ones in clinical trials as potential kinase inhibitors: A Review. Pharmacol. Pharm., 2012, 3(1), 62-71.
[http://dx.doi.org/10.4236/pp.2012.31010]
[41]
Nepali, K.; Sharma, S.; Sharma, M.; Bedi, P.M.S.; Dhar, K.L. Rational approaches, design strategies, structure activity relationship and mechanistic insights for anticancer hybrids. Eur. J. Med. Chem., 2014, 77, 422-487.
[http://dx.doi.org/10.1016/j.ejmech.2014.03.018] [PMID: 24685980]
[42]
Ibrahim, H.S.; Abou-Seri, S.M.; Abdel-Aziz, H.A. 3-Hydrazinoindolin-2-one derivatives: Chemical classification and investigation of their targets as anticancer agents. Eur. J. Med. Chem., 2016, 122, 366-381.
[http://dx.doi.org/10.1016/j.ejmech.2016.06.034] [PMID: 27391135]
[43]
Han, K.; Zhou, Y.; Liu, F.; Guo, Q.; Wang, P.; Yang, Y.; Song, B.; Liu, W.; Yao, Q.; Teng, Y.; Yu, P. Design, synthesis and in vitro cytotoxicity evaluation of 5-(2-carboxyethenyl)isatin derivatives as anticancer agents. Bioorg. Med. Chem. Lett., 2014, 24(2), 591-594.
[http://dx.doi.org/10.1016/j.bmcl.2013.12.001] [PMID: 24360564]
[44]
Ravula, P.; Vamaraju, H.B.; Paturi, M.; Chandra Jn, N.S.; Kolli, S. Design, synthesis, in silico toxicity prediction, molecular docking, and evaluation of novel pyrazole derivatives as potential antiproliferative agents. EXCLI J., 2016, 15, 187-202.
[http://dx.doi.org/10.17179/excli2016-103] [PMID: 27103897]
[45]
Abdullaziz, M.A.; Abdel-Mohsen, H.T.; El Kerdawy, A.M.; Ragab, F.A.F.; Ali, M.M.; Abu-Bakr, S.M.; Girgis, A.S.; El Diwani, H.I. Design, synthesis, molecular docking and cytotoxic evaluation of novel 2-furybenzimidazoles as VEGFR-2 inhibitors. Eur. J. Med. Chem., 2017, 136, 315-329.
[http://dx.doi.org/10.1016/j.ejmech.2017.04.068] [PMID: 28505536]
[46]
Shahin, M.I.; Abou El Ella, D.A.; Ismail, N.S.M.; Abouzid, K.A.M. Design, synthesis and biological evaluation of type-II VEGFR-2 inhibitors based on quinoxaline scaffold. Bioorg. Chem., 2014, 56, 16-26.
[http://dx.doi.org/10.1016/j.bioorg.2014.05.010] [PMID: 24922538]
[47]
Paramashivam, S.K.; Elayaperumal, K.; Natarajan, B.B.; Ramamoorthy, M.D.; Balasubramanian, S.; Dhiraviam, K.N. In silico pharmacokinetic and molecular docking studies of small molecules derived from Indigofera aspalathoides Vahl targeting receptor tyrosine kinases. Bioinformation, 2015, 11(2), 73-84.
[http://dx.doi.org/10.6026/97320630011073] [PMID: 25848167]
[48]
Remko, M.; Boha, A. Kova’cˇikova, L. Molecular structure, pKa, lipophilicity, solubility, absorption, polar surface area, and blood brain barrier penetration of some antiangiogenic agents. Struct. Chem., 2011, 22, 635-648.
[http://dx.doi.org/10.1007/s11224-011-9741-z]
[49]
Mele, T.; Generali, D.; Fox, S.; Brizzi, M.P.; Bersiga, A.; Milani, M.; Allevi, G.; Bonardi, S.; Aguggini, S.; Volante, M.; Dogliotti, L.; Bottini, A.; Harris, A.; Berruti, A. Anti-angiogenic effect of tamoxifen combined with epirubicin in breast cancer patients. Breast Cancer Res. Treat., 2010, 123(3), 795-804.
[http://dx.doi.org/10.1007/s10549-010-1063-0] [PMID: 20680681]
[50]
Shoemaker, R.H. The NCI60 human tumour cell line anticancer drug screen. Nat. Rev. Cancer, 2006, 6(10), 813-823.
[http://dx.doi.org/10.1038/nrc1951] [PMID: 16990858]
[51]
Boyd, M.R.; Paull, K.D. Some practical considerations and applications of the national cancer institute in vitro anticancer drug discovery screen. Drug Dev. Res., 1995, 34(2), 91-109.
[http://dx.doi.org/10.1002/ddr.430340203]
[52]
Havrylyuk, D.; Zimenkovsky, B.; Vasylenko, O.; Gzella, A.; Lesyk, R. Synthesis of new 4-thiazolidinone-, pyrazoline-, and isatin-based conjugates with promising antitumor activity. J. Med. Chem., 2012, 55(20), 8630-8641.
[http://dx.doi.org/10.1021/jm300789g] [PMID: 22992049]
[53]
Ali, M.R.; Kumar, S.; Shalmali, N.; Afzal, O.; Azim, S.; Chanana, D.; Alam, O.; Paudel, Y.N.; Sharma, M.; Bawa, S. Development of thiazole-5-carboxylate derivatives as selective inhibitors of monoacylglycerol lipase as target in cancer. Mini Rev. Med. Chem., 2019, 19(5), 410-423.
[http://dx.doi.org/10.2174/1389557518666180702103542] [PMID: 29962341]
[54]
Afzal, O.; Akhtar, M.S.; Kumar, S.; Ali, M.R.; Jaggi, M.; Bawa, S. Hit to lead optimization of a series of N-[4-(1,3-benzothiazol-2-yl)phenyl]acetamides as monoacylglycerol lipase inhibitors with potential anticancer activity. Eur. J. Med. Chem., 2016, 121, 318-330.
[http://dx.doi.org/10.1016/j.ejmech.2016.05.038] [PMID: 27267002]
[55]
Holbeck, S.L.; Collins, J.M.; Doroshow, J.H. Analysis of food and drug administration-approved anticancer agents in the NCI60 panel of human tumor cell lines. Mol. Cancer Ther., 2010, 9(5), 1451-1460.
[http://dx.doi.org/10.1158/1535-7163.MCT-10-0106] [PMID: 20442306]
[56]
Grewal, A.S. Isatin derivatives with several biological activities. Int. J. Pharm. Res., 2014, 6(1), 1-7.
[57]
Pattan, S.R.; Ali, M.S.; Pattan, J.S.; Purohit, S.S.; Reddy, V.V.K.; Nataraj, B.R. Synthesis and microbiological evaluation of 2-acetanilido-4-arylthiazole derivatives. Indian J. Chem., 2006, 45B, 1929-1932.
[http://dx.doi.org/10.1002/chin.200650143]
[58]
Sander, T.; Freyss, J.; von Korff, M.; Rufener, C. DataWarrior: an open-source program for chemistry aware data visualization and analysis. J. Chem. Inf. Model., 2015, 55(2), 460-473.
[http://dx.doi.org/10.1021/ci500588j] [PMID: 25558886]
[59]
Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feeney, P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev., 2001, 46(1-3), 3-26.
[http://dx.doi.org/10.1016/S0169-409X(00)00129-0] [PMID: 11259830]
[60]
Hou, T.; Wang, J.; Zhang, W.; Xu, X. ADME evaluation in drug discovery. 6. Can oral bioavailability in humans be effectively predicted by simple molecular property-based rules? J. Chem. Inf. Model., 2007, 47(2), 460-463.
[http://dx.doi.org/10.1021/ci6003515] [PMID: 17381169]
[61]
Meanwell, N.A. Improving drug candidates by design: a focus on physicochemical properties as a means of improving compound disposition and safety. Chem. Res. Toxicol., 2011, 24(9), 1420-1456.
[http://dx.doi.org/10.1021/tx200211v] [PMID: 21790149]
[62]
Modi, S.J.; Kulkarni, V.M. Vascular endothelial growth factor receptor (VEGFR-2)/KDR inhibitors: Medicinal chemistry perspective. Med. Drug Discov., 2019, 2, 100009.
[http://dx.doi.org/10.1016/j.medidd.2019.100009]
[63]
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.
[http://dx.doi.org/10.1111/cbdd.13493] [PMID: 30689282]
[64]
Liu, R.; Meng, Y.; Zhu, M.; Zhai, H.; Lv, W.; Wen, T.; Jin, N. Study on novel PtNP-sorafenib and its interaction with VEGFR2. The J. Biochem., 2021, 170(3), 411-417.
[http://dx.doi.org/10.1093/jb/mvab053] [PMID: 33944931]
[65]
Capelli, A.M.; Costantino, G. Unbinding pathways of VEGFR2 inhibitors revealed by steered molecular dynamics. J. Chem. Inf. Model., 2014, 54(11), 3124-3136.
[http://dx.doi.org/10.1021/ci500527j] [PMID: 25299731]
[66]
Zhang, L.; Wang, X.; Feng, J.; Jia, Y.; Xu, F.; Xu, W. Discovery of novel vascular endothelial growth factor receptor 2 inhibitors: a virtual screening approach. Chem. Biol. Drug Des., 2012, 80(6), 893-901.
[http://dx.doi.org/10.1111/cbdd.12036] [PMID: 22913881]
[67]
Ahmed, M.F.; Santali, E.Y.; El-Haggar, R. Novel piperazine-chalcone hybrids and related pyrazoline analogues targeting VEGFR-2 kinase; design, synthesis, molecular docking studies, and anticancer evaluation. J. Enzyme Inhib. Med. Chem., 2021, 36(1), 307-318.
[http://dx.doi.org/10.1080/14756366.2020.1861606] [PMID: 33349069]
[68]
Aneja, B.; Arif, R.; Perwez, A.; Napoleon, J.V.; Hasan, P.; Rizvi, M.M.A.; Azam, A. Rahisuddin; Abid, M. N-substituted 1,2,3-triazolyl-appended indole-chalcone hybrids as potential DNA intercalators endowed with antioxidant and anticancer properties. ChemistrySelect, 2018, 3(9), 2638-2645.
[http://dx.doi.org/10.1002/slct.201702913]
[69]
Bavadi, M.; Niknama, K.; Shahraki, O. Novel pyrrole derivatives bearing sulfonamide groups: Synthesis in vitro cytotoxicity evaluation, molecular docking and DFT study. J. Mol. Struct., 2017, 1146, 242-253.
[http://dx.doi.org/10.1016/j.molstruc.2017.06.003]
[70]
Mishra, A.; Mehdi, S.J.; Irshad, M.; Ali, A.; Sardar, M.; Rizvi, M.M.A. Effect of biologically synthesized silver nanoparticles on human cancer cells. Sci. Adv. Mater., 2012, 4(12), 1200-1206.
[http://dx.doi.org/10.1166/sam.2012.1414]
[71]
Khorsandi, L.; Orazizadeh, M.; Niazvand, F.; Abbaspour, M.R.; Mansouri, E.; Khodadadi, A. Quercetin induces apoptosis and necroptosis in MCF-7 breast cancer cells. Bratisl. Lek Listy, 2017, 118(2), 123-128.
[http://dx.doi.org/10.4149/BLL_2017_025] [PMID: 28814095]
[72]
Zhang, H.W.; Hu, J.J.; Fu, R.Q.; Liu, X.; Zhang, Y.H.; Li, J.; Liu, L.; Li, Y.N.; Deng, Q.; Luo, Q.S.; Ouyang, Q.; Gao, N. Flavonoids inhibit cell proliferation and induce apoptosis and autophagy through downregulation of PI3Kγ mediated PI3K/AKT/mTOR/p70S6K/ULK signaling pathway in human breast cancer cells. Sci. Rep., 2018, 8(1), 11255.
[http://dx.doi.org/10.1038/s41598-018-29308-7] [PMID: 30050147]

Rights & Permissions Print Cite
Article Metrics
20
1
© 2024 Bentham Science Publishers | Privacy Policy