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Current Medicinal Chemistry

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ISSN (Online): 1875-533X

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Research Article

Novel Natural Inhibitors for Glioblastoma by Targeting Epidermal Growth Factor Receptor and Phosphoinositide 3-kinase

In Press, (this is not the final "Version of Record"). Available online 09 April, 2024
Author(s): Atta Ullah, Saeed Ullah, Muhammad Waqas, Majid Khan, Najeeb Ur Rehman, Asaad Khalid, Afnan Jan, Shahkaar Aziz, Muhammad Naeem, Sobia Ahsan Halim*, Ajmal Khan* and Ahmed Al-Harrasi*
Published on: 09 April, 2024

DOI: 10.2174/0109298673293279240404080046

Price: $95

Abstract

Background/Aim: Glioblastoma is an extensively malignant neoplasm of the brain that predominantly impacts the human population. To address the challenge of glioblastoma, herein, we have searched for new drug-like candidates by extensive computational and biochemical investigations.

Method: Approximately 950 compounds were virtually screened against the two most promising targets of glioblastoma, i.e., epidermal growth factor receptor (EGFR) and phosphoinositide 3-kinase (PI3K). Based on highly negative docking scores, excellent binding capabilities and good pharmacokinetic properties, eight and seven compounds were selected for EGFR and PI3K, respectively.

Results: Among those hits, four natural products (SBEH-40, QUER, QTME-12, and HCFR) exerted dual inhibitory effects on EGFR and PI3K in our in-silico analysis; therefore, their capacity to suppress the cell proliferation was assessed in U87 cell line (type of glioma cell line). The compounds SBEH-40, QUER, andQTME-12 exhibited significant anti-proliferative capability with IC50 values of 11.97 ± 0.73 μM, 28.27 ± 1.52 μM, and 22.93 ± 1.63 μM respectively, while HCFR displayed weak inhibitory potency (IC50 = 74.97 ± 2.30 μM).

Conclusion: This study has identified novel natural products that inhibit the progression of glioblastoma; however, further examinations of these molecules are required in animal and tissue models to better understand their downstream targeting mechanisms.

[1]
Krex, D.; Klink, B.; Hartmann, C.; von Deimling, A.; Pietsch, T.; Simon, M.; Sabel, M.; Steinbach, J.P.; Heese, O.; Reifenberger, G.; Weller, M.; Schackert, G. Long-term survival with glioblastoma multiforme. Brain, 2007, 130(10), 2596-2606.
[http://dx.doi.org/10.1093/brain/awm204] [PMID: 17785346]
[2]
Toraih, E.A.; Aly, N.M.; Abdallah, H.Y.; Qahtani, A.S.A.; Shaalan, A.A.M.; Hussein, M.H.; Fawzy, M.S. MicroRNA-target cross-talks: Key players in glioblastoma multiforme. Tumour Biol., 2017, 39(11), 1010428317726842.
[http://dx.doi.org/10.1177/1010428317726842] [PMID: 29110584]
[3]
Holland, E.C. Glioblastoma multiforme: The terminator. Proc. Natl. Acad. Sci. USA, 2000, 97(12), 6242-6244.
[http://dx.doi.org/10.1073/pnas.97.12.6242] [PMID: 10841526]
[4]
Adamson, C.; Kanu, O.O.; Mehta, A.I.; Di, C.; Lin, N.; Mattox, A.K.; Bigner, D.D. Glioblastoma multiforme: A review of where we have been and where we are going. Expert Opin. Investig. Drugs, 2009, 18(8), 1061-1083.
[http://dx.doi.org/10.1517/13543780903052764] [PMID: 19555299]
[5]
Keles, G.E.; Anderson, B.; Berger, M.S. The effect of extent of resection on time to tumor progression and survival in patients with glioblastoma multiforme of the cerebral hemisphere. Surg. Neurol., 1999, 52(4), 371-379.
[http://dx.doi.org/10.1016/S0090-3019(99)00103-2] [PMID: 10555843]
[6]
Ejaz, K.; Suaib, N.B.M.; Kamal, M.S.; Rahim, M.S.M.; Rana, N. Segmentation method of deterministic feature clustering for identification of brain tumor using MRI. IEEE Access, 2023, 11, 39695-39712.
[http://dx.doi.org/10.1109/ACCESS.2023.3263798]
[7]
Parsa, A.T.; Wachhorst, S.; Lamborn, K.R.; Prados, M.D.; McDermott, M.W.; Berger, M.S.; Chang, S.M. Prognostic significance of intracranial dissemination of glioblastoma multiforme in adults. J. Neurosurg., 2005, 102(4), 622-628.
[http://dx.doi.org/10.3171/jns.2005.102.4.0622] [PMID: 15871503]
[8]
Natha, S.; Laila, U.; Gashim, I.A.; Mahboob, K.; Saeed, M.N.; Noaman, K.M. Automated brain tumor identification in biomedical radiology images: A multi-model ensemble deep learning approach. Appl. Sci., 2024, 14(5), 2210.
[http://dx.doi.org/10.3390/app14052210]
[9]
Roth, J.G.; Elvidge, A.R. Glioblastoma multiforme: A clinical survey. J. Neurosurg., 1960, 17(4), 736-750.
[http://dx.doi.org/10.3171/jns.1960.17.4.0736] [PMID: 14439403]
[10]
Barbagallo, G.M.V.; Jenkinson, M.D.; Brodbelt, A.R. ‘Recurrent’ glioblastoma multiforme, when should we reoperate? Br. J. Neurosurg., 2008, 22(3), 452-455.
[http://dx.doi.org/10.1080/02688690802182256] [PMID: 18568742]
[11]
Sanli, A.; Turkoglu, E.; Dolgun, H.; Sekerci, Z. Unusual manifestations of primary Glioblastoma Multiforme: A report of three cases. Surg. Neurol. Int., 2010, 1(1), 87.
[http://dx.doi.org/10.4103/2152-7806.74146] [PMID: 21206896]
[12]
Robinson, G.W.; Orr, B.A.; Gajjar, A. Complete clinical regression of a BRAF V600E-mutant pediatric glioblastoma multiforme after BRAF inhibitor therapy. BMC Cancer, 2014, 14(1), 258.
[http://dx.doi.org/10.1186/1471-2407-14-258] [PMID: 24725538]
[13]
Sasmita, A.O.; Wong, Y.P.; Ling, A.P.K. Biomarkers and therapeutic advances in glioblastoma multiforme. Asia Pac. J. Clin. Oncol., 2018, 14(1), 40-51.
[http://dx.doi.org/10.1111/ajco.12756] [PMID: 28840962]
[14]
Hodges, L.C.; Smith, J.L.; Garrett, A.; Tate, S. Prevalence of glioblastoma multiforme in subjects with prior therapeutic radiation. J. Neurosci. Nurs., 1992, 24(2), 79-83.
[15]
Zhao, H.; Wang, J.; Shao, W.; Wu, C.; Chen, Z.; To, S.T.; Li, W. Recent advances in the use of PI3K inhibitors for glioblastoma multiforme: Current preclinical and clinical development. Mol. Cancer, 2017, 16(1), 100.
[http://dx.doi.org/10.1186/s12943-017-0670-3] [PMID: 28592260]
[16]
Ramaiah, M.J.; Kumar, K.R. mTOR-Rictor-EGFR axis in oncogenesis and diagnosis of glioblastoma multiforme. Mol. Biol. Rep., 2021, 48(5), 4813-4835.
[http://dx.doi.org/10.1007/s11033-021-06462-2] [PMID: 34132942]
[17]
Lötsch, D.; Steiner, E.; Holzmann, K.; Kreinecker, S.S.; Pirker, C.; Hlavaty, J.; Petznek, H.; Hegedus, B.; Garay, T.; Mohr, T.; Sommergruber, W.; Grusch, M.; Berger, W. Major vault protein supports glioblastoma survival and migration by upregulating the EGFR/PI3K signalling axis. Oncotarget, 2013, 4(11), 1904-1918.
[http://dx.doi.org/10.18632/oncotarget.1264] [PMID: 24243798]
[18]
Fan, Q.-W.; Weiss, W.A. Targeting the RTK-PI3K-mTOR axis in malignant glioma: Overcoming resistance. Curr. Top. Microbiol. Immunol., 2011, 2, 279-296.
[19]
Akhavan, D.; Cloughesy, T.F.; Mischel, P.S. mTOR signaling in glioblastoma: Lessons learned from bench to bedside. Neuro-oncol., 2010, 12(8), 882-889.
[http://dx.doi.org/10.1093/neuonc/noq052] [PMID: 20472883]
[20]
Newton, H.B. Molecular neuro-oncology and development of targeted therapeutic strategies for brain tumors. Part 2: PI3K/Akt/PTEN, mTOR, SHH/PTCH and angiogenesis. Expert Rev. Anticancer Ther., 2004, 4(1), 105-128.
[http://dx.doi.org/10.1586/14737140.4.1.105] [PMID: 14748662]
[21]
Prasad, G.; Sottero, T.; Yang, X.; Mueller, S.; James, C.D.; Weiss, W.A.; Polley, M.Y.; Ozawa, T.; Berger, M.S.; Aftab, D.T.; Prados, M.D.; Haas-Kogan, D.A. Inhibition of PI3K/mTOR pathways in glioblastoma and implications for combination therapy with temozolomide. Neuro-oncol., 2011, 13(4), 384-392.
[http://dx.doi.org/10.1093/neuonc/noq193] [PMID: 21317208]
[22]
Tuncel, G.; Kalkan, R. Receptor tyrosine kinase-Ras-PI 3 kinase-Akt signaling network in glioblastoma multiforme. Med. Oncol., 2018, 35(9), 122.
[http://dx.doi.org/10.1007/s12032-018-1185-5] [PMID: 30078108]
[23]
Crespo, S.; Kind, M.; Arcaro, A. The role of the PI3K/AKT/mTOR pathway in brain tumor metastasis. J. Cancer Metastasis Treat., 2016, 2(3), 80-89.
[http://dx.doi.org/10.20517/2394-4722.2015.72]
[24]
Jalalvand, A.R. Chemometrics in investigation of small molecule-biomacromolecule interactions: A review. Int. J. Biol. Macromol., 2021, 181, 478-493.
[http://dx.doi.org/10.1016/j.ijbiomac.2021.03.184] [PMID: 33798569]
[25]
Glaysher, S.; Bolton, L.M.; Johnson, P.; Atkey, N.; Dyson, M.; Torrance, C.; Cree, I.A. Targeting EGFR and PI3K pathways in ovarian cancer. Br. J. Cancer, 2013, 109(7), 1786-1794.
[http://dx.doi.org/10.1038/bjc.2013.529] [PMID: 24022196]
[26]
Zaryouh, H.; De Pauw, I.; Baysal, H.; Peeters, M.; Vermorken, J.B.; Lardon, F.; Wouters, A. Recent insights in the PI3K/Akt pathway as a promising therapeutic target in combination with EGFR-targeting agents to treat head and neck squamous cell carcinoma. Med. Res. Rev., 2022, 42(1), 112-155.
[http://dx.doi.org/10.1002/med.21806] [PMID: 33928670]
[27]
Markham, A. Copanlisib: first global approval. Drugs, 2017, 77(18), 2057-2062.
[http://dx.doi.org/10.1007/s40265-017-0838-6] [PMID: 29127587]
[28]
Dreyling, M.; Morschhauser, F.; Bouabdallah, K.; Bron, D.; Cunningham, D.; Assouline, S.E.; Verhoef, G.; Linton, K.; Thieblemont, C.; Vitolo, U.; Hiemeyer, F.; Giurescu, M.; Vargas, G.J.; Gorbatchevsky, I.; Liu, L.; Koechert, K.; Peña, C.; Neves, M.; Childs, B.H.; Zinzani, P.L. Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma. Ann. Oncol., 2017, 28(9), 2169-2178.
[http://dx.doi.org/10.1093/annonc/mdx289] [PMID: 28633365]
[29]
Markham, A. Idelalisib: First global approval. Drugs, 2014, 74(14), 1701-1707.
[http://dx.doi.org/10.1007/s40265-014-0285-6] [PMID: 25187123]
[30]
Lu, S.; Dong, X.; Jian, H.; Chen, J.; Chen, G.; Sun, Y.; Ji, Y.; Wang, Z.; Shi, J.; Lu, J. Am. Soc. Clin. Oncol., 2022, 40(27), 3162.
[31]
Kumar, A.; Bhatia, R.; Chawla, P.; Anghore, D.; Saini, V.; Rawal, R.K. Copanlisib: Novel PI3K inhibitor for the treatment of lymphoma. Anti-Cancer Agents Med. Chem., 2020, 20(10), 1158-1172.
[32]
Shirley, M.; Keam, S.J. Aumolertinib: A review in non-small cell lung cancer. Drugs, 2022, 82(5), 577-584.
[http://dx.doi.org/10.1007/s40265-022-01695-2] [PMID: 35305259]
[33]
Michaels, S.A.; Hulverson, M.A.; Whitman, G.R.; Tran, L.T.; Choi, R.; Fan, E.; McNamara, C.W.; Love, M.S.; Ojo, K.K. Repurposing the kinase inhibitor mavelertinib for giardiasis therapy. Antimicrob. Agents Chemother., 2022, 66(7), e00017-22.
[http://dx.doi.org/10.1128/aac.00017-22] [PMID: 35703552]
[34]
Sun, Y.; Chu, L.; Wang, H.; Peng, H.; Liu, J. Inhibitory effect of gefitinib derivative LPY-9 on human glioma. Mol. Med. Rep., 2021, 24(3), 623.
[http://dx.doi.org/10.3892/mmr.2021.12262] [PMID: 34212976]
[35]
Tan, J.; Li, M.; Zhong, W.; Hu, C.; Gu, Q.; Xie, Y. Tyrosine kinase inhibitors show different anti-brain metastases efficacy in NSCLC: A direct comparative analysis of icotinib, gefitinib, and erlotinib in a nude mouse model. Oncotarget, 2017, 8(58), 98771-98781.
[http://dx.doi.org/10.18632/oncotarget.21936] [PMID: 29228726]
[36]
Rich, J.N.; Reardon, D.A.; Peery, T.; Dowell, J.M.; Quinn, J.A.; Penne, K.L.; Wikstrand, C.J.; Van Duyn, L.B.; Dancey, J.E.; McLendon, R.E.; Kao, J.C.; Stenzel, T.T.; Rasheed, A.B.K.; Uhlig, T.S.E.; Herndon, J.E., II; Vredenburgh, J.J.; Sampson, J.H.; Friedman, A.H.; Bigner, D.D.; Friedman, H.S. Phase II trial of gefitinib in recurrent glioblastoma. J. Clin. Oncol., 2004, 22(1), 133-142.
[http://dx.doi.org/10.1200/JCO.2004.08.110] [PMID: 14638850]
[37]
Yang, Q.; Modi, P.; Newcomb, T.; Quéva, C.; Gandhi, V. Idelalisib: First-in-class PI3K delta inhibitor for the treatment of chronic lymphocytic leukemia, small lymphocytic leukemia, and follicular lymphoma. Clin. Cancer Res., 2015, 21(7), 1537-1542.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-2034] [PMID: 25670221]
[38]
Kumar, N.; Lal, N.; Nemaysh, V.; Luthra, P.M. Design, synthesis, DNA binding studies and evaluation of anticancer potential of novel substituted biscarbazole derivatives against human glioma U87 MG cell line. Bioorg. Chem., 2020, 100, 103911.
[http://dx.doi.org/10.1016/j.bioorg.2020.103911] [PMID: 32502918]
[39]
Karve, A.S.; Desai, J.M.; Dave, N.; Draper, W.T.M.; Gudelsky, G.A.; Phoenix, T.N.; DasGupta, B.; Sengupta, S.; Plas, D.R.; Desai, P.B. Potentiation of temozolomide activity against glioblastoma cells by aromatase inhibitor letrozole. Cancer Chemother. Pharmacol., 2022, 90(4), 345-356.
[http://dx.doi.org/10.1007/s00280-022-04469-5] [PMID: 36050497]
[40]
Li, X.; Wu, C.; Chen, N.; Gu, H.; Yen, A.; Cao, L.; Wang, E.; Wang, L. PI3K/Akt/mTOR signaling pathway and targeted therapy for glioblastoma. Oncotarget, 2016, 7(22), 33440-33450.
[http://dx.doi.org/10.18632/oncotarget.7961] [PMID: 26967052]
[41]
Fan, Q.W.; Cheng, C.K.; Nicolaides, T.P.; Hackett, C.S.; Knight, Z.A.; Shokat, K.M.; Weiss, W.A. A dual phosphoinositide-3-kinase α/mTOR inhibitor cooperates with blockade of epidermal growth factor receptor in PTEN-mutant glioma. Cancer Res., 2007, 67(17), 7960-7965.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-2154] [PMID: 17804702]
[42]
Lino, M.M.; Merlo, A. PI3Kinase signaling in glioblastoma. J. Neurooncol., 2011, 103(3), 417-427.
[http://dx.doi.org/10.1007/s11060-010-0442-z] [PMID: 21063898]
[43]
Demir, Y.; Ceylan, H.; Türkeş, C.; Beydemir, Ş. Molecular docking and inhibition studies of vulpinic, carnosic and usnic acids on polyol pathway enzymes. J. Biomol. Struct. Dyn., 2022, 40(22), 12008-12021.
[http://dx.doi.org/10.1080/07391102.2021.1967195] [PMID: 34424822]
[44]
Tokalı, F.S.; Demir, Y.; Türkeş, C.; Dinçer, B.; Beydemir, Ş. Novel acetic acid derivatives containing quinazolin-4(3 H )-one ring: Synthesis, in vitro, and in silico evaluation of potent aldose reductase inhibitors. Drug Dev. Res., 2023, 84(2), 275-295.
[http://dx.doi.org/10.1002/ddr.22031] [PMID: 36598092]
[45]
Rose, P.W.; Bi, C.; Bluhm, W.F.; Christie, C.H.; Dimitropoulos, D.; Dutta, S.; Green, R.K.; Goodsell, D.S.; Prlić, A.; Quesada, M.; Quinn, G.B.; Ramos, A.G.; Westbrook, J.D.; Young, J.; Zardecki, C.; Berman, H.M.; Bourne, P.E. The RCSB Protein Data Bank: New resources for research and education. Nucleic Acids Res., 2013, 41(Database issue), D475-D482.
[PMID: 23193259]
[46]
Stamos, J.; Sliwkowski, M.X.; Eigenbrot, C. Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor. J. Biol. Chem., 2002, 277(48), 46265-46272.
[http://dx.doi.org/10.1074/jbc.M207135200] [PMID: 12196540]
[47]
Walker, E.H.; Pacold, M.E.; Perisic, O.; Stephens, L.; Hawkins, P.T.; Wymann, M.P.; Williams, R.L. Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine. Mol. Cell, 2000, 6(4), 909-919.
[http://dx.doi.org/10.1016/S1097-2765(05)00089-4] [PMID: 11090628]
[48]
Peters, M.B.; Yang, Y.; Wang, B.; Molnár, F.L.; Weaver, M.N.; Merz Jr., K.M. Structural survey of zinc-containing proteins and development of the zinc AMBER force field (ZAFF). J. Chem. Theory Comput., 2010, 6(9), 2935-2947.
[http://dx.doi.org/10.1021/ct1002626] [PMID: 20856692]
[49]
Rajhi, A.A.M.H.; Qanash, H.; Almuhayawi, M.S.; Jaouni, A.S.K.; Bakri, M.M.; Ganash, M.; Salama, H.M.; Selim, S.; Abdelghany, T.M. Molecular interaction studies and phytochemical characterization of Mentha pulegium L. constituents with multiple biological utilities as antioxidant, antimicrobial, anticancer and anti-hemolytic agents. Molecules, 2022, 27(15), 4824.
[http://dx.doi.org/10.3390/molecules27154824] [PMID: 35956775]
[50]
Aziz, M.; Ejaz, S.A.; Tamam, N.; Siddique, F.; Riaz, N.; Qais, F.A.; Chtita, S.; Iqbal, J. Identification of potent inhibitors of NEK7 protein using a comprehensive computational approach. Sci. Rep., 2022, 12(1), 6404.
[http://dx.doi.org/10.1038/s41598-022-10253-5] [PMID: 35436996]
[51]
Chan, W.K.B.; Olson, K.M.; Wotring, J.W.; Sexton, J.Z.; Carlson, H.A.; Traynor, J.R. In silico analysis of SARS-CoV-2 proteins as targets for clinically available drugs. Sci. Rep., 2022, 12(1), 5320.
[http://dx.doi.org/10.1038/s41598-022-08320-y] [PMID: 35351926]
[52]
Scholz, C.; Knorr, S.; Hamacher, K.; Schmidt, B. DOCKTITE-A highly versatile step-by-step workflow for covalent docking and virtual screening in the molecular operating environment. J. Chem. Inf. Model., 2015, 55(2), 398-406.
[http://dx.doi.org/10.1021/ci500681r] [PMID: 25541749]
[53]
Ullah, A.; Waqas, M.; Halim, S.A.; Daud, M.; Jan, A.; Khan, A.; Harrasi, A.A. Sirtuin 1 inhibition: A promising avenue to suppress cancer progression through small inhibitors design. J. Biomol. Struct. Dyn., 2023, 1-17.
[http://dx.doi.org/10.1080/07391102.2023.2252898] [PMID: 37661778]
[54]
Corbeil, C.R.; Williams, C.I.; Labute, P. Variability in docking success rates due to dataset preparation. J. Comput. Aided Mol. Des., 2012, 26(6), 775-786.
[http://dx.doi.org/10.1007/s10822-012-9570-1] [PMID: 22566074]
[55]
Béchet, E.; Minnebo, H.; Moës, N.; Burgardt, B. Improved implementation and robustness study of the X-FEM for stress analysis around cracks. Int. J. Numer. Methods Eng., 2005, 64(8), 1033-1056.
[http://dx.doi.org/10.1002/nme.1386]
[56]
Waqas, M.; Halim, S.A.; Ullah, A.; Ali, A.A.M.; Khalid, A.; Abdalla, A.N.; Khan, A.; Harrasi, A.A. Multi-Fold computational analysis to discover novel putative inhibitors of isethionate sulfite-lyase (isla) from Bilophila wadsworthia: Combating colorectal cancer and inflammatory bowel diseases. Cancers, 2023, 15(3), 901.
[http://dx.doi.org/10.3390/cancers15030901] [PMID: 36765864]
[57]
Shi, C.; Chen, J.; Xiao, B.; Kang, X.; Lao, X.; Zheng, H. Discovery of NDM-1 inhibitors from natural products. J. Glob. Antimicrob. Resist., 2019, 18, 80-87.
[http://dx.doi.org/10.1016/j.jgar.2019.02.003] [PMID: 30763762]
[58]
Chopra, H.; Bibi, S.; Kumar, S.; Khan, M.S.; Kumar, P.; Singh, I. Preparation and evaluation of chitosan/PVA based hydrogel films loaded with honey for wound healing application. Gels, 2022, 8(2), 111.
[http://dx.doi.org/10.3390/gels8020111] [PMID: 35200493]
[59]
Gfeller, D.; Grosdidier, A.; Wirth, M.; Daina, A.; Michielin, O.; Zoete, V. SwissTargetPrediction: A web server for target prediction of bioactive small molecules. Nucleic Acids Res., 2014, 42(W1), W32-W38.
[http://dx.doi.org/10.1093/nar/gku293] [PMID: 24792161]
[60]
Mayr, A.; Klambauer, G.; Unterthiner, T.; Steijaert, M.; Wegner, J.K.; Ceulemans, H.; Clevert, D.A.; Hochreiter, S. Large-scale comparison of machine learning methods for drug target prediction on ChEMBL. Chem. Sci., 2018, 9(24), 5441-5451.
[http://dx.doi.org/10.1039/C8SC00148K] [PMID: 30155234]
[61]
Da, C.; Kireev, D. Structural protein-ligand interaction fingerprints (SPLIF) for structure-based virtual screening: Method and benchmark study. J. Chem. Inf. Model., 2014, 54(9), 2555-2561.
[http://dx.doi.org/10.1021/ci500319f] [PMID: 25116840]
[62]
Sravika, N.; Priya, S.; Divya, N.; Jyotsna, P.M.S.; Anusha, P.; Kudumula, N.; Bai, S.A. Swiss ADME properties screening of the phytochemical compounds present in Bauhinia acuminata. J. Pharmacogn. Phytochem., 2021, 10(4), 411-419.
[http://dx.doi.org/10.22271/phyto.2021.v10.i4e.14193]
[63]
Daina, A.; Michielin, O.; Zoete, V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep., 2017, 7(1), 42717.
[http://dx.doi.org/10.1038/srep42717] [PMID: 28256516]
[64]
Kumar, P.; Nagarajan, A.; Uchil, P.D. Analysis of cell viability by the MTT assay. Cold Spring Harb. Protoc., 2018, 2018(6), pdb.prot095505.
[http://dx.doi.org/10.1101/pdb.prot095505] [PMID: 29858338]
[65]
Plumb, J.A. Cell sensitivity assays: the MTT assay. Methods Mol Med., 1999, 28, 25-30.
[66]
Sever, B.; Altıntop, M.D.; Demir, Y.; Yılmaz, N.; Çiftçi, A.G.; Beydemir, Ş.; Özdemir, A. Identification of a new class of potent aldose reductase inhibitors: Design, microwave-assisted synthesis, in vitro and in silico evaluation of 2-pyrazolines. Chem. Biol. Interact., 2021, 345, 109576.
[http://dx.doi.org/10.1016/j.cbi.2021.109576] [PMID: 34252406]
[67]
Buza, A.; Türkeş, C.; Arslan, M.; Demir, Y.; Dincer, B.; Nixha, A.R.; Beydemir, Ş. Discovery of novel benzenesulfonamides incorporating 1,2,3-triazole scaffold as carbonic anhydrase I, II, IX, and XII inhibitors. Int. J. Biol. Macromol., 2023, 239, 124232.
[http://dx.doi.org/10.1016/j.ijbiomac.2023.124232] [PMID: 37001773]
[68]
He, J.J.; Zhang, W.H.; Liu, S.L.; Chen, Y.F.; Liao, C.X.; Shen, Q.Q.; Hu, P. Activation of β-adrenergic receptor promotes cellular proliferation in human glioblastoma. Oncol. Lett., 2017, 14(3), 3846-3852.
[http://dx.doi.org/10.3892/ol.2017.6653] [PMID: 28927156]
[69]
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.
[http://dx.doi.org/10.1016/0022-1759(83)90303-4] [PMID: 6606682]
[70]
Meerloo, V.J.; Kaspers, G.J.; Cloos, J. Cell sensitivity assays: the MTT assay. Methods Mol Biol., 2011, 731, 237-245.
[71]
Ma, D.L.; Chan, D.S.H.; Leung, C.H. Molecular docking for virtual screening of natural product databases. Chem. Sci., 2011, 2(9), 1656-1665.
[http://dx.doi.org/10.1039/C1SC00152C]
[72]
Kakakhan, C.; Türkeş, C.; Güleç, Ö.; Demir, Y.; Arslan, M.; Özkemahlı, G.; Beydemir, Ş. Exploration of 1,2,3-triazole linked benzenesulfonamide derivatives as isoform selective inhibitors of human carbonic anhydrase. Bioorg. Med. Chem., 2023, 77, 117111.
[http://dx.doi.org/10.1016/j.bmc.2022.117111] [PMID: 36463726]
[73]
Wirsching, H.-G.; Weller, M. Glioblastoma. Malignant brain tumors: State-of-the-art treatment Springer Nature, 2017, 265-288.
[74]
Ohgaki, H.; Kleihues, P. The definition of primary and secondary glioblastoma. Clin. Cancer Res., 2013, 19(4), 764-772.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-3002] [PMID: 23209033]
[75]
Alexander, B.M.; Cloughesy, T.F. Adult glioblastoma. J. Clin. Oncol., 2017, 35(21), 2402-2409.
[http://dx.doi.org/10.1200/JCO.2017.73.0119] [PMID: 28640706]
[76]
Sami, A.; Karsy, M. Targeting the PI3K/AKT/mTOR signaling pathway in glioblastoma: Novel therapeutic agents and advances in understanding. Tumour Biol., 2013, 34(4), 1991-2002.
[http://dx.doi.org/10.1007/s13277-013-0800-5] [PMID: 23625692]
[77]
Koul, D.; Shen, R.; Bergh, S.; Sheng, X.; Shishodia, S.; Lafortune, T.A.; Lu, Y.; de Groot, J.F.; Mills, G.B.; Yung, W.K.A. Inhibition of Akt survival pathway by a small- molecule inhibitor in human glioblastoma. Mol. Cancer Ther., 2006, 5(3), 637-644.
[http://dx.doi.org/10.1158/1535-7163.MCT-05-0453] [PMID: 16546978]
[78]
Mischel, P.S.; Cloughesy, T.F. Targeted molecular therapy of GBM. Brain Pathol., 2003, 13(1), 52-61.
[http://dx.doi.org/10.1111/j.1750-3639.2003.tb00006.x] [PMID: 12580545]
[79]
Yu, L. Jessica, Wei.; Liu, P. Attacking the PI3K/Akt/mToR signaling pathway for targeted therapeutic treatment in human cancer. Semin. Cancer Biol., 2022, 85, 69-94.
[80]
Koul, D.; Shen, R.; Kim, Y.W.; Kondo, Y.; Lu, Y.; Bankson, J.; Ronen, S.M.; Kirkpatrick, D.L.; Powis, G.; Yung, W.K.A. Cellular and in vivo activity of a novel PI3K inhibitor, PX-866, against human glioblastoma. Neuro-oncol., 2010, 12(6), 559-569.
[http://dx.doi.org/10.1093/neuonc/nop058] [PMID: 20156803]
[81]
Gijtenbeek, R.G.P.; Noort, v.d.V.; Aerts, J.G.J.V.; Brekel, S.v.d.J.A.; Smit, E.F.; Krouwels, F.H.; Wilschut, F.A.; Hiltermann, T.J.N.; Timens, W.; Schuuring, E.; Janssen, J.D.J.; Goosens, M.; Berg, v.d.P.M.; de Langen, A.J.; Stigt, J.A.; van den Borne, B.E.E.M.; Groen, H.J.M.; van Geffen, W.H.; van der Wekken, A.J. Randomised controlled trial of first-line tyrosine-kinase inhibitor (TKI) versus intercalated TKI with chemotherapy for EGFR -mutated nonsmall cell lung cancer. ERJ Open Res., 2022, 8(4), 00239-2022.
[http://dx.doi.org/10.1183/23120541.00239-2022] [PMID: 36267895]
[82]
Zhang, H. Osimertinib making a breakthrough in lung cancer targeted therapy. OncoTargets Ther., 2016, 9, 5489-5493.
[http://dx.doi.org/10.2147/OTT.S114722] [PMID: 27660466]
[83]
Nagasaka, M.; Zhu, V.W.; Lim, S.M.; Greco, M.; Wu, F.; Ou, S.H.I. Beyond osimertinib: The development of third- generation EGFR tyrosine kinase inhibitors for advanced EGFR+ NSCLC. J. Thorac. Oncol., 2021, 16(5), 740-763.
[http://dx.doi.org/10.1016/j.jtho.2020.11.028] [PMID: 33338652]
[84]
Paez, J.G.; Jänne, P.A.; Lee, J.C.; Tracy, S.; Greulich, H.; Gabriel, S.; Herman, P.; Kaye, F.J.; Lindeman, N.; Boggon, T.J.; Naoki, K.; Sasaki, H.; Fujii, Y.; Eck, M.J.; Sellers, W.R.; Johnson, B.E.; Meyerson, M. EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science, 2004, 304(5676), 1497-1500.
[http://dx.doi.org/10.1126/science.1099314] [PMID: 15118125]
[85]
Greig, S.L. Osimertinib: first global approval. Drugs, 2016, 76(2), 263-273.
[http://dx.doi.org/10.1007/s40265-015-0533-4] [PMID: 26729184]
[86]
Rawat, A.; Reddy, V.B.A. Recent advances on anticancer activity of coumarin derivatives. European J. Med. Chem. Reports, 2022, 5, 100038.
[http://dx.doi.org/10.1016/j.ejmcr.2022.100038]
[87]
Xiang, Y.; Zhang, Q.; Wei, S.; Huang, C.; Li, Z.; Gao, Y. Paeoniflorin: A monoterpene glycoside from plants of Paeoniaceae family with diverse anticancer activities. J. Pharm. Pharmacol., 2020, 72(4), 483-495.
[http://dx.doi.org/10.1111/jphp.13204] [PMID: 31858611]
[88]
Zubair, T.; Bandyopadhyay, D. Small molecule EGFR inhibitors as anti-cancer agents: Discovery, mechanisms of action, and opportunities. Int. J. Mol. Sci., 2023, 24(3), 2651.
[http://dx.doi.org/10.3390/ijms24032651] [PMID: 36768973]
[89]
Nozhat, Z.; Heydarzadeh, S.; Khalaji, S.M.; Wang, S.; Iqbal, M.Z.; Kong, X. Advanced biomaterials for human glioblastoma multiforme (GBM) drug delivery. Biomater. Sci., 2023, 11(12), 4094-4131.
[http://dx.doi.org/10.1039/D2BM01996E] [PMID: 37073998]
[90]
Zhang, F.Y.; Hu, Y.; Que, Z.Y.; Wang, P.; Liu, Y.H.; Wang, Z.H.; Xue, Y.X. Shikonin inhibits the migration and invasion of human glioblastoma cells by targeting phosphorylated β-catenin and phosphorylated PI3K/Akt: A potential mechanism for the anti-glioma efficacy of a traditional Chinese herbal medicine. Int. J. Mol. Sci., 2015, 16(10), 23823-23848.
[http://dx.doi.org/10.3390/ijms161023823] [PMID: 26473829]
[91]
Atiq, A.; Parhar, I. Anti-neoplastic potential of flavonoids and polysaccharide phytochemicals in glioblastoma. Molecules, 2020, 25(21), 4895.
[http://dx.doi.org/10.3390/molecules25214895] [PMID: 33113890]

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