Screening of Azadirachta indica phytoconstituents as GSK-3β inhibitor and its implication in neuroblastoma: molecular docking, molecular dynamics, MM-PBSA binding energy, and in-vitro study

References

• Alzohairy, M. A. (2016). Therapeutics role of Azadirachta indica (neem) and their active constituents in diseases prevention and treatment. Evidence-Based Complementary and Alternative Medicine : eCAM, 2016, 7382506. https://doi.org/10.1155/2016/7382506
   PubMed Web of Science ®Google Scholar
• Amos, S., Lin, S., Stouffer, M., Wandling, E., Noland, L., Huanyun, D., Jean‐Loius, D., & Darkwah, B. (2021). Gedunin, a novel HSP90 inhibitor, decreases cellular growth and induces apoptosis in glioblastoma cell lines. The FASEB Journal, 35(S1), 35. https://doi.org/10.1096/fasebj.2021.35.S1.02456
   Google Scholar
• Atkinson, J. M., Rank, K. B., Zeng, Y., Capen, A., Yadav, V., Manro, J. R., Engler, T. A., & Chedid, M. (2015). Activating the Wnt/β-catenin pathway for the treatment of melanoma-application of LY2090314, a novel selective inhibitor of glycogen synthase kinase-3. PloS One, 10(4), e0125028. https://doi.org/10.1371/journal.pone.0125028
   PubMed Web of Science ®Google Scholar
• Bahmad, H. F., Chalhoub, R. M., Harati, H., Bou-Gharios, J., Assi, S., Ballout, F., Monzer, A., Msheik, H., Araji, T., Elajami, M. K., Ghanem, P., Chamaa, F., Kadara, H., Abou-Antoun, T., Daoud, G., Fares, Y., & Abou-Kheir, W. (2021). Tideglusib attenuates growth of neuroblastoma cancer stem/progenitor cells in vitro and in vivo by specifically targeting GSK-3β. Pharmacological Reports, 73(1), 211–226.
   Google Scholar
• Baker, N. A., Sept, D., Joseph, S., Holst, M. J., & McCammon, J. A. (2001). Electrostatics of nanosystems: Application to microtubules and the ribosome. Proceedings of the National Academy of Sciences, 98(18), 10037–10041. https://doi.org/10.1073/pnas.181342398
   PubMed Web of Science ®Google Scholar
• Banarescu, L., Bonial, C., Cai, S., Georgescu, M., Griffitt, K., Hermjakob, U., Knight, K., Koehn, P., Palmer, M., & Schneider, N. (2013, August). Abstract meaning representation for sembanking. In Proceedings of the 7th Linguistic Annotation Workshop and Interoperability with Discourse (pp. 178–186).
   Google Scholar
• Berendsen, H. J., van der Spoel, D., & van Drunen, R. (1995). GROMACS: A message-passing parallel molecular dynamics implementation. Computer Physics Communications, 91(1–3), 43–56. https://doi.org/10.1016/0010-4655(95)00042-E
   Web of Science ®Google Scholar
• Beurel, E., Grieco, S. F., & Jope, R. S. (2015). Glycogen synthase kinase-3 (GSK3): regulation, actions, and diseases. Pharmacology & Therapeutics, 148, 114–131. https://doi.org/10.1016/j.pharmthera.2014.11.016
   PubMed Web of Science ®Google Scholar
• Bhardwaj, V. K., Singh, R., Das, P., & Purohit, R. (2021). Evaluation of acridinedione analogs as potential SARS-CoV-2 main protease inhibitors and their comparison with repurposed anti-viral drugs. Computers in Biology and Medicine, 128, 104117.
   PubMed Web of Science ®Google Scholar
• Bhardwaj, V. K., Singh, R., Sharma, J., Rajendran, V., Purohit, R., & Kumar, S. (2020). Identification of bioactive molecules from tea plant as SARS-CoV-2 main protease inhibitors. Journal of Biomolecular Structure and Dynamics, 39(10), 3449–3458.
   PubMed Web of Science ®Google Scholar
• Bhardwaj, V. K., Singh, R., Sharma, J., Rajendran, V., Purohit, R., & Kumar, S. (2021). Bioactive molecules of Tea as potential inhibitors for RNA-dependent RNA polymerase of SARS-CoV-2. Frontiers in Medicine, 8, 684020.
   PubMed Web of Science ®Google Scholar
• Bhat, R. V., Andersson, U., Andersson, S., Knerr, L., Bauer, U., & Sundgren-Andersson, A. K. (2018). The conundrum of GSK3 inhibitors: Is it the dawn of a new beginning? Journal of Alzheimer's Disease : JAD, 64(s1), S547–S554.
   PubMed Web of Science ®Google Scholar
• Boonstra, S., Onck, P. R., & van der Giessen, E. (2016). CHARMM TIP3P water model suppresses peptide folding by solvating the unfolded state. The Journal of Physical Chemistry. B, 120(15), 3692–3698.
   PubMed Web of Science ®Google Scholar
• Brooks, B. R., Bruccoleri, R. E., Olafson, B. D., States, D. J., Swaminathan, S. A., & Karplus, M. (1983). CHARMM: A program for macromolecular energy, minimization, and dynamics calculations. Journal of Computational Chemistry, 4(2), 187–217. https://doi.org/10.1002/jcc.540040211
   Web of Science ®Google Scholar
• Bustanji, Y., Taha, M. O., Almasri, I. M., Al-Ghussein, M. A., Mohammad, M. K., & Alkhatib, H. S. (2009). Inhibition of glycogen synthase kinase by curcumin: Investigation by simulated molecular docking and subsequent in vitro/in vivo evaluation. Journal of Enzyme Inhibition and Medicinal Chemistry, 24(3), 771–778.
   PubMed Web of Science ®Google Scholar
• Daggupati, T., Pamanji, R., & Yeguvapalli, S. (2018). In silico screening and identification of potential GSK3β inhibitors. Journal of Receptor and Signal Transduction Research, 38(4), 279–289.
   PubMed Web of Science ®Google Scholar
• Daina, A., Michielin, O., & Zoete, V. (2014). iLOGP: A simple, robust, and efficient description of n-octanol/water partition coefficient for drug design using the GB/SA approach. Journal of Chemical Information and Modeling, 54(12), 3284–3301. https://doi.org/10.1021/ci500467k
   PubMed Web of Science ®Google Scholar
• Daina, A., Michielin, O., & Zoete, V. (2017). SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7(1), 42717–42713. https://doi.org/10.1038/srep42717
   PubMed Web of Science ®Google Scholar
• Daina, A., & Zoete, V. (2016). A boiled‐egg to predict gastrointestinal absorption and brain penetration of small molecules. ChemMedChem, 11(11), 1117–1121.
   PubMed Web of Science ®Google Scholar
• Dallakyan, S., & Olson, A. J. (2015). Small-molecule library screening by docking with PyRx. In Chemical biology (pp. 243–250). New York, NY: Humana Press.
   Google Scholar
• Darshit, B. S., & Ramanathan, M. (2016). Activation of AKT1/GSK-3 β/β-Catenin–TRIM11/Survivin pathway by novel GSK-3 β inhibitor promotes neuron cell survival: Study in differentiated SH-SY5Y cells in OGD model. Molecular Neurobiology, 53(10), 6716–6729. https://doi.org/10.1007/s12035-015-9598-z
   PubMed Web of Science ®Google Scholar
• Dickey, A., Schleicher, S., Leahy, K., Hu, R., Hallahan, D., & Thotala, D. K. (2011). GSK-3β inhibition promotes cell death, apoptosis, and in vivo tumor growth delay in neuroblastoma Neuro-2A cell line. Journal of Neuro-Oncology, 104(1), 145–153.
   PubMed Web of Science ®Google Scholar
• Domoto, T., Pyko, I. V., Furuta, T., Miyashita, K., Uehara, M., Shimasaki, T., Nakada, M., & Minamoto, T. (2016). Glycogen synthase kinase‐3β is a pivotal mediator of cancer invasion and resistance to therapy. Cancer Science, 107(10), 1363–1372.
   PubMed Web of Science ®Google Scholar
• Duda, P., Wiśniewski, J., Wójtowicz, T., Wójcicka, O., Jaśkiewicz, M., Drulis-Fajdasz, D., Rakus, D., McCubrey, J. A., & Gizak, A. (2018). Targeting GSK3 signaling as a potential therapy of neurodegenerative diseases and aging. Expert Opinion on Therapeutic Targets, 22(10), 833–848.
   PubMed Web of Science ®Google Scholar
• Elangovan, N. D., Dhanabalan, A. K., Gunasekaran, K., Kandimalla, R., & Sankarganesh, D. (2020). Screening of potential drug for Alzheimer’s disease: A computational study with GSK-3 β inhibition through virtual screening, docking, and molecular dynamics simulation. Journal of Biomolecular Structure and Dynamics, 1–15. https://doi.org/10.1080/07391102.2020.1805362
   Google Scholar
• Eldar-Finkelman, H., & Martinez, A. (2011). GSK-3 inhibitors: Preclinical and clinical focus on CNS. Frontiers in Molecular Neuroscience, 4, 32.
   PubMed Web of Science ®Google Scholar
• Fiol, C. J., Mahrenholz, A. M., Wang, Y., Roeske, R. W., & Roach, P. J. (1987). Formation of protein kinase recognition sites by covalent modification of the substrate. Molecular mechanism for the synergistic action of casein kinase II and glycogen synthase kinase 3. The Journal of Biological Chemistry, 262(29), 14042–14048.
   PubMed Web of Science ®Google Scholar
• Gasteiger, J., & Marsili, M. (1980). Iterative partial equalization of orbital electronegativity—a rapid access to atomic charges. Tetrahedron, 36(22), 3219–3228. https://doi.org/10.1016/0040-4020(80)80168-2
   Web of Science ®Google Scholar
• Gould, T. D., Einat, H., Bhat, R., & Manji, H. K. (2004). AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test. The International Journal of Neuropsychopharmacology, 7(4), 387–390. https://doi.org/10.1017/S1461145704004535
   PubMed Web of Science ®Google Scholar
• Haldar, S., Mulani, F. A., Aarthy, T., Dandekar, D. S., & Thulasiram, H. V. (2014). Expedient preparative isolation and tandem mass spectrometric characterization of C-seco triterpenoids from Neem oil. Journal of Chromatography. A, 1366, 1–14.
   PubMed Web of Science ®Google Scholar
• Hao, F., Kumar, S., Yadav, N., & Chandra, D. (2014). Neem components as potential agents for cancer prevention and treatment. Biochimica et Biophysica Acta, 1846(1), 247–257. https://doi.org/10.1016/j.bbcan.2014.07.002
   PubMed Web of Science ®Google Scholar
• Hasan, A., Haque, E., Hameed, R., Maier, P. N., Irfan, S., Kamil, M., Nazir, A., & Mir, S. S. (2020). Hsp90 inhibitor gedunin causes apoptosis in A549 lung cancer cells by disrupting Hsp90:Beclin-1:Bcl-2 interaction and downregulating autophagy. Life Sciences, 256, 118000. https://doi.org/10.1016/j.lfs.2020.118000
   PubMed Web of Science ®Google Scholar
• Huang, H. C., Tang, D., Xu, K., & Jiang, Z. F. (2014). Curcumin attenuates amyloid-β-induced tau hyperphosphorylation in human neuroblastoma SH-SY5Y cells involving PTEN/Akt/GSK-3β signaling pathway. Journal of Receptor and Signal Transduction Research, 34(1), 26–37.
   PubMed Web of Science ®Google Scholar
• Iwaloye, O., Elekofehinti, O. O., Oluwarotimi, E. A., Kikiowo, B. I., & Fadipe, T. M. (2020). Insight into glycogen synthase kinase-3β inhibitory activity of phyto-constituents from Melissa officinalis: In silico studies. In Silico Pharmacology, 8(1), 2–13. https://doi.org/10.1007/s40203-020-00054-x
   PubMedGoogle Scholar
• Ji, Y., Dai, F., Yan, S., Shi, J. Y., & Zhou, B. (2019). Identification of catechol-type diphenylbutadiene as a tyrosinase-activated pro-oxidative chemosensitizer against melanoma A375 cells via glutathione S-transferase inhibition. Journal of Agricultural and Food Chemistry, 67(32), 9060–9069.
   PubMed Web of Science ®Google Scholar
• Johnsen, J. I., Dyberg, C., & Wickström, M. (2019). Neuroblastoma—A neural crest derived embryonal malignancy. Frontiers in Molecular Neuroscience, 12, 9.
   PubMed Web of Science ®Google Scholar
• Johnson, J., Venugopal, A., Kwatra, D., Roby, K., Godwin, A., & Anant, S. (2014). Gedunin, a novel HSP-90 inhibitor, synergizes with cisplatin and paclitaxel to inhibit growth of chemoresistant ovarian cancer cell lines. Proceedings of the 105th Annual Meeting of the American Association for Cancer Research.Cancer Research, 74(14).
   Google Scholar
• Kanninen, K., White, A. R., Koistinaho, J., & Malm, T. (2011). Targeting glycogen synthase kinase-3β for therapeutic benefit against oxidative stress in Alzheimer's disease: Involvement of the Nrf2-ARE Pathway. International Journal of Alzheimer's Disease, 2011, 985085. https://doi.org/10.4061/2011/985085
   PubMedGoogle Scholar
• Kishore T, K. K., Ganugula, R., Gade, D. R., Reddy, G. B., & Nagini, S. (2016). Gedunin abrogates aldose reductase, PI3K/Akt/mToR, and NF-κB signaling pathways to inhibit angiogenesis in a hamster model of oral carcinogenesis. Tumour Biology : The Journal of the International Society for Oncodevelopmental Biology and Medicine, 37(2), 2083–2093. https://doi.org/10.1007/s13277-015-4003-0
   PubMedGoogle Scholar
• Kotliarova, S., Pastorino, S., Kovell, L. C., Kotliarov, Y., Song, H., Zhang, W., Bailey, R., Maric, D., Zenklusen, J. C., Lee, J., & Fine, H. A. (2008). Glycogen synthase kinase-3 inhibition induces glioma cell death through c-MYC, nuclear factor-κB, and glucose regulation. Cancer Research, 68(16), 6643–6651.
   PubMed Web of Science ®Google Scholar
• Kramer, T., Schmidt, B., & Lo Monte, F. (2012). Small-molecule inhibitors of GSK-3: Structural insights and their application to Alzheimer's disease models. International Journal of Alzheimer's Disease, 2012, 381029. https://doi.org/10.1155/2012/381029
   PubMedGoogle Scholar
• Kumari, R., Kumar, R., Open Source Drug Discovery Consortium, & Lynn, A. (2014). g_mmpbsa-a GROMACS tool for high-throughput MM-PBSA calculations. Journal of Chemical Information and Modeling, 54(7), 1951–1962. https://doi.org/10.1021/ci500020m
   PubMed Web of Science ®Google Scholar
• Kunnimalaiyaan, S., Schwartz, V. K., Jackson, I. A., Gamblin, T. C., & Kunnimalaiyaan, M. (2018). Antiproliferative and apoptotic effect of LY2090314, a GSK-3 inhibitor, in neuroblastoma in vitro. BMC Cancer, 18(1), 560–568.
   PubMedGoogle Scholar
• Lee, S., Tran, A., Allsopp, M., Lim, J. B., Hénin, J., & Klauda, J. B. (2014). CHARMM36 united atom chain model for lipids and surfactants. The Journal of Physical Chemistry. B, 118(2), 547–556.
   PubMed Web of Science ®Google Scholar
• Li, H., Wu, J. G., Zhang, H. W., Wang, W., Zhang, Y. X., & Zhang, J. N. (2018). Inhibition of proliferation, invasion and migration in U-251 MG glioblastoma cell line by gedunin. International Journal of Pharmacology, 14(4), 522–527. https://doi.org/10.3923/ijp.2018.522.527
   Web of Science ®Google Scholar
• Linding, R., Jensen, L. J., Ostheimer, G. J., van Vugt, M. A. T. M., Jørgensen, C., Miron, I. M., Diella, F., Colwill, K., Taylor, L., Elder, K., Metalnikov, P., Nguyen, V., Pasculescu, A., Jin, J., Park, J. G., Samson, L. D., Woodgett, J. R., Russell, R. B., Bork, P., Yaffe, M. B., & Pawson, T. (2007). Systematic discovery of in vivo phosphorylation networks. Cell, 129(7), 1415–1426.
   PubMed Web of Science ®Google Scholar
• MacAulay, K., Hajduch, E., Blair, A. S., Coghlan, M. P., Smith, S. A., & Hundal, H. S. (2003). Use of lithium and SB‐415286 to explore the role of glycogen synthase kinase‐3 in the regulation of glucose transport and glycogen synthase. European Journal of Biochemistry, 270(18), 3829–3838.
   PubMedGoogle Scholar
• Maqbool, M., & Hoda, N. (2017). GSK3 inhibitors in the therapeutic development of diabetes, cancer and neurodegeneration: Past, present and future. Current Pharmaceutical Design, 23(29), 4332–4350.
   PubMed Web of Science ®Google Scholar
• Mathuram, T. L., Ravikumar, V., Reece, L. M., Karthik, S., Sasikumar, C. S., & Cherian, K. M. (2016). Tideglusib induces apoptosis in human neuroblastoma IMR32 cells, provoking sub-G0/G1 accumulation and ROS generation. Environmental Toxicology and Pharmacology, 46, 194–205.
   PubMed Web of Science ®Google Scholar
• McCubrey, J. A., Lertpiriyapong, K., Steelman, L. S., Abrams, S. L., Cocco, L., Ratti, S., Martelli, A. M., Candido, S., Libra, M., Montalto, G., Cervello, M., Gizak, A., & Rakus, D. (2017). Regulation of GSK-3 activity by curcumin, berberine and resveratrol: Potential effects on multiple diseases. Advances in Biological Regulation, 65, 77–88.
   PubMedGoogle Scholar
• McMillin, D. W., Ooi, M., Delmore, J., Negri, J., Hayden, P., Mitsiades, N., Jakubikova, J., Maira, S.-M., Garcia-Echeverria, C., Schlossman, R., Munshi, N. C., Richardson, P. G., Anderson, K. C., & Mitsiades, C. S. (2009). Antimyeloma activity of the orally bioavailable dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235. Cancer Research, 69(14), 5835–5842. https://doi.org/10.1158/0008-5472.CAN-08-4285
   PubMed Web of Science ®Google Scholar
• Montagnani, V., & Stecca, B. (2019). Role of protein kinases in hedgehog pathway control and implications for cancer therapy. Cancers, 11(4), 449.
   PubMed Web of Science ®Google Scholar
• Ngok-Ngam, P., Watcharasit, P., Thiantanawat, A., & Satayavivad, J. (2013). Pharmacological inhibition of GSK3 attenuates DNA damage-induced apoptosis via reduction of p53 mitochondrial translocation and Bax oligomerization in neuroblastoma SH-SY5Y cells. Cellular & Molecular Biology Letters, 18(1), 58–74.
   PubMed Web of Science ®Google Scholar
• Nisha, C. M., Kumar, A., Vimal, A., Bai, B. M., Pal, D., & Kumar, A. (2016). Docking and ADMET prediction of few GSK-3 inhibitors divulges 6-bromoindirubin-3-oxime as a potential inhibitor. Journal of Molecular Graphics & Modelling, 65, 100–107.
   PubMed Web of Science ®Google Scholar
• Nwokwu, C. D. U., Samarakoon, S. R., Karunaratne, D. N., Katuvawila, N. P., Pamunuwa, G. K., Ediriweera, M. K., & Tennekoon, K. H. (2017). Induction of apoptosis in response to improved gedunin by liposomal nano-encapsulation in human non-small-cell lung cancer (NCI-H292) cell line. Tropical Journal of Pharmaceutical Research, 16(9), 2079–2087. https://doi.org/10.4314/tjpr.v16i9.6
   Web of Science ®Google Scholar
• Pandey, M. K., & DeGrado, T. R. (2016). Glycogen synthase kinase-3 (GSK-3)-targeted therapy and imaging. Theranostics, 6(4), 571–593. https://doi.org/10.7150/thno.14334
   PubMed Web of Science ®Google Scholar
• Pires, D. E., Blundell, T. L., & Ascher, D. B. (2015). pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. Journal of Medicinal Chemistry, 58(9), 4066–4072.
   PubMed Web of Science ®Google Scholar
• Pizarro, J. G., Folch, J., Esparza, J. L., Jordan, J., Pallàs, M., & Camins, A. (2009). A molecular study of pathways involved in the inhibition of cell proliferation in neuroblastoma B65 cells by the GSK‐3 inhibitors lithium and SB‐415286. Journal of Cellular and Molecular Medicine, 13(9b), 3906–3917.
   PubMed Web of Science ®Google Scholar
• Poulose, S. M., Harris, E. D., & Patil, B. S. (2006). Antiproliferative effects of citrus limonoids against human neuroblastoma and colonic adenocarcinoma cells. Nutrition and Cancer, 56(1), 103–112. https://doi.org/10.1207/s15327914nc5601_14
   PubMed Web of Science ®Google Scholar
• Rahman, M. A., Kim, N. H., Yang, H., & Huh, S. O. (2012). Angelicin induces apoptosis through intrinsic caspase-dependent pathway in human SH-SY5Y neuroblastoma cells. Molecular and Cellular Biochemistry, 369(1-2), 95–104.
   PubMed Web of Science ®Google Scholar
• Rappé, A. K., Casewit, C. J., Colwell, K. S., Goddard, W. A., III, & Skiff, W. M. (1992). UFF, a full periodic table force field for molecular mechanics and molecular dynamics simulations. Journal of the American Chemical Society, 114(25), 10024–10035. https://doi.org/10.1021/ja00051a040
   Web of Science ®Google Scholar
• Rizzieri, D. A., Cooley, S., Odenike, O., Moonan, L., Chow, K. H., Jackson, K., Wang, X., Brail, L., & Borthakur, G. (2016). An open-label phase 2 study of glycogen synthase kinase-3 inhibitor LY2090314 in patients with acute leukemia. Leukemia & Lymphoma, 57(8), 1800–1806. https://doi.org/10.3109/10428194.2015.1122781
   PubMed Web of Science ®Google Scholar
• Sahai, R., Bhattacharjee, A., Shukla, V. N., Yadav, P., Hasanain, M., Sarkar, J., Narender, T., & Mitra, K. (2020). Gedunin isolated from the mangrove plant Xylocarpus granatum exerts its anti-proliferative activity in ovarian cancer cells through G2/M-phase arrest and oxidative stress-mediated intrinsic apoptosis. Apoptosis : An International Journal on Programmed Cell Death, 25(7-8), 481–499.
   PubMed Web of Science ®Google Scholar
• Saitoh, M., Kunitomo, J., Kimura, E., Hayase, Y., Kobayashi, H., Uchiyama, N., Kawamoto, T., Tanaka, T., Mol, C. D., Dougan, D. R., Textor, G. S., Snell, G. P., & Itoh, F. (2009). Design, synthesis and structure-activity relationships of 1,3,4-oxadiazole derivatives as novel inhibitors of glycogen synthase kinase-3beta . Bioorganic & Medicinal Chemistry, 17(5), 2017–2029. https://doi.org/10.1016/j.bmc.2009.01.019
   PubMed Web of Science ®Google Scholar
• Salmaso, V., & Moro, S. (2018). Bridging molecular docking to molecular dynamics in exploring ligand-protein recognition process: An overview. Frontiers in Pharmacology, 9, 923.
   PubMed Web of Science ®Google Scholar
• Sarkar, L., Putchala, R. K., Safiriyu, A. A., & Das Sarma, J. (2020). Azadirachtaindica A. Juss ameliorates mouse hepatitis virus-induced neuroinflammatory demyelination by modulating cell-to-cell fusion in an experimental animal model of multiple sclerosis. Frontiers in Cellular Neuroscience, 14, 116. https://doi.org/10.3389/fncel.2020.00116
   PubMed Web of Science ®Google Scholar
• Sharma, J., Bhardwaj, V. K., Singh, R., Rajendran, V., Purohit, R., & Kumar, S. (2021). An in-silico evaluation of different bioactive molecules of tea for their inhibition potency against non structural protein-15 of SARS-CoV-2. Food Chemistry, 346, 128933. https://doi.org/10.1016/j.foodchem.2020.128933
   PubMed Web of Science ®Google Scholar
• Shi, Y.-S., Zhang, Y., Li, H.-T., Wu, C.-H., El-Seedi, H. R., Ye, W.-K., Wang, Z.-W., Li, C.-B., Zhang, X.-F., & Kai, G.-Y. (2020). Limonoids from Citrus: Chemistry, anti-tumor potential, and other bioactivities. Journal of Functional Foods, 75, 104213. https://doi.org/10.1016/j.jff.2020.104213
   Web of Science ®Google Scholar
• Singh, R., Bhardwaj, V. K., Das, P., & Purohit, R. (2021). A computational approach for rational discovery of inhibitors for non-structural protein 1 of SARS-CoV-2. Computers in Biology and Medicine, 135, 104555. https://doi.org/10.1016/j.compbiomed.2021.104555
   PubMed Web of Science ®Google Scholar
• Singh, R., Bhardwaj, V. K., Sharma, J., Purohit, R., & Kumar, S. (2021). In-silico evaluation of bioactive compounds from tea as potential SARS-CoV-2 nonstructural protein 16 inhibitors. Journal of Traditional and Complementary Medicine. https://doi.org/10.1016/j.jtcme.2021.05.005. ISSN 2225–4110
   Google Scholar
• Sophia, J., Kiran Kishore T, K., Kowshik, J., Mishra, R., & Nagini, S. (2016). Nimbolide, a neem limonoid inhibits phosphatidyl inositol-3 kinase to activate glycogen synthase kinase-3β in a hamster model of oral oncogenesis. Scientific Reports, 6(1), 22192–22113. https://doi.org/10.1038/srep22192
   PubMedGoogle Scholar
• Subramani, R., Gonzalez, E., Nandy, S. B., Arumugam, A., Camacho, F., Medel, J., Alabi, D., & Lakshmanaswamy, R. (2017). Gedunin inhibits pancreatic cancer by altering sonic hedgehog signaling pathway. Oncotarget, 8(7), 10891–10904.
   PubMedGoogle Scholar
• Sutherland, C. (2011). What are the bona fide GSK3 substrates? International Journal of Alzheimer's Disease, 2011, 505607. https://doi.org/10.4061/2011/505607
   PubMedGoogle Scholar
• Tanagala, K. K., Baba, A. B., Kowshik, J., Reddy, G. B., & Nagini, S. (2018). Gedunin, a neem limonoid in combination with epalrestat inhibits cancer hallmarks by attenuating aldose reductase-driven oncogenic signaling in SCC131 oral cancer cells. Anti-Cancer Agents in Medicinal Chemistry, 18(14), 2042–2052. https://doi.org/10.2174/1871520618666180731093433
   PubMed Web of Science ®Google Scholar
• Tate, E. H., Wilder, M. E., Cram, L. S., & Wharton, W. (1983). A method for staining 3T3 cell nuclei with propidium iodide in hypotonic solution. Cytometry, 4(3), 211–215. https://doi.org/10.1002/cyto.990040304
   PubMedGoogle Scholar
• Ugolkov, A. V., Bondarenko, G. I., Dubrovskyi, O., Berbegall, A. P., Navarro, S., Noguera, R., O'Halloran, T. V., Hendrix, M. J., Giles, F. J., & Mazar, A. P. (2018). 9-ING-41, a small molecule Glycogen Synthase Kinase-3 inhibitor, is active in neuroblastoma. Anti-Cancer Drugs, 29(8), 717–724.
   PubMed Web of Science ®Google Scholar
• Valvezan, A. J., & Klein, P. S. (2012). GSK-3 and Wnt signaling in neurogenesis and bipolar disorder. Frontiers in Molecular Neuroscience, 5, 1.
   PubMed Web of Science ®Google Scholar
• Van Drie, J. H. (2007). Computer-aided drug design: The next 20 years. Journal of Computer-Aided Molecular Design, 21(10–11), 591–601. https://doi.org/10.1007/s10822-007-9142-y
   PubMed Web of Science ®Google Scholar
• Veeraraghavan, J., Aravindan, S., Natarajan, M., Awasthi, V., Herman, T. S., & Aravindan, N. (2011). Neem leaf extract induces radiosensitization in human neuroblastoma xenograft through modulation of apoptotic pathway. Anticancer Research, 31(1), 161–170.
   PubMed Web of Science ®Google Scholar
• Venna, V. R., Benashski, S. E., Chauhan, A., & McCullough, L. D. (2015). Inhibition of glycogen synthase kinase-3β enhances cognitive recovery after stroke: The role of TAK1. Learning & Memory (Cold Spring Harbor, N.Y.), 22(7), 336–343.
   PubMed Web of Science ®Google Scholar
• Xiong, G., Wu, Z., Yi, J., Fu, L., Yang, Z., Hsieh, C., Yin, M., Zeng, X., Wu, C., Lu, A., Chen, X., Hou, T., & Cao, D. (2021). ADMETlab 2.0: An integrated online platform for accurate and comprehensive predictions of ADMET properties. Nucleic Acids Research, 49(W1), W5–W14. https://doi.org/10.1093/nar/gkab255
   PubMed Web of Science ®Google Scholar