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Research Articles

Synthesis, in vitro evaluation and molecular docking studies of novel naphthoisoxazolequinone carboxamide hybrids as potential antitumor agents

, ORCID Icon, ORCID Icon, , & ORCID Icon
Pages 4960-4983 | Received 27 Jan 2022, Accepted 23 Jun 2022, Published online: 13 Jul 2022

References

  • World Health Organization, “Cancer,” last modified September 21, 2021, http://www.who.int/news-room/fact-sheets/detail/cancer (accessed November 06, 2021).
  • J. Schüz, C. Espina, and C. P. Wild, “Primary Prevention: A Need for Concerted Action,” Molecular Oncology 13, no. 3 (2019): 567–78. doi:10.1002/1878-0261.12432.
  • World Health Organization, “Global Cancer Observatory: Cancer Today, Lyon: International Agency for Research on Cancer”, https://gco.iarc.fr/today (accessed March 26, 2021).
  • World Health Organization, “Cancer Tomorrow, Lyon: International Agency for Research on Cancer”, https://gco.iarc.fr/tomorrow/home (accessed July 24, 2021).
  • M. Manickam, P. R. Boggu, J. Cho, Y. J. Nam, S. J. Lee, and S. H. Jung, “Investigation of Chemical Reactivity of 2-Alkoxy-1,4-Naphthoquinones and Their Anticancer Activity,” Bioorganic & Medicinal Chemistry Letters 28, no. 11 (2018): 2023–8. doi:10.1016/j.bmcl.2018.04.060.
  • A. Ghods, J. Gilbert, J. R. Baker, C. C. Russell, J. A. Sakoff, and A. McCluskey, “A Focused Library Synthesis and Cytotoxicity of Quinones Derived from the Natural Product Bolinaquinone,” Royal Society Open Science 5, no. 4 (2018): 171189. doi:10.1098/rsos.171189.
  • F. Wang, X. Yao, Y. Zhang, and J. Tang, " “Synthesis, Biological Function and Evaluation of Shikonin in Cancer Therapy,” Fitoterapia 134 (2019): 329–39. doi:10.1016/j.fitote.2019.03.005.
  • B. Pang, J. De Jong, X. Qiao, L. F. A. Wessels, and J. Neefjes, " “Chemical Profiling of the Genome with anti-Cancer Drugs Defines Target Specificities,” Nature Chemical Biology 11, no. 7 (2015): 472–80. doi:10.1038/nchembio.1811.
  • X. Liang, Q. Wu, S. Luan, Z. Yin, C. He, L. Yin, Y. Zou, Z. Yuan, L. Li, X. Song, et al, “A Comprehensive Review of Topoisomerase Inhibitors as Anticancer Agents in the past Decade,” European Journal of Medicinal Chemistry 171 (2019): 129–68. doi:10.1016/j.ejmech.2019.03.034.
  • I. Hueso-Falcón, Á. Amesty, L. Anaissi-Afonso, I. Lorenzo-Castrillejo, F. Machín, and A. Estévez-Braun, “Synthesis and Biological Evaluation of Naphthoquinone-Coumarin Conjugates as Topoisomerase II Inhibitors,” Bioorganic & Medicinal Chemistry Letters 27, no. 3 (2017): 484–9. doi:10.1016/j.bmcl.2016.12.040.
  • V. Marković, A. Janićijević, T. Stanojković, B. Kolundžija, D. Sladić, M. Vujčić, B. Janović, L. Joksović, P. T. Djurdjević, N. Todorović, et al, “Synthesis, Cytotoxic Activity and DNA-Interaction Studies of Novel Anthraquinone-Thiosemicarbazones with Tautomerizable Methylene Group,” European Journal of Medicinal Chemistry 64 (2013): 228–38. doi:10.1016/j.ejmech.2013.03.071.
  • V. Kuete, A. R. Nanfack Donfack, A. T. Mbaveng, M. Zeino, P. Tane, and T. Efferth, “Cytotoxicity of Anthraquinones from the Roots of Pentas Schimperi towards Multi-Factorial Drug-Resistant Cancer Cells,” Investigational New Drugs 33, no. 4 (2015): 861–9. doi:10.1007/s10637-015-0268-9.
  • T. B. Gontijo, R. P. de Freitas, F. S. Emery, L. F. Pedrosa, J. B. Vieira Neto, B. C. Cavalcanti, C. Pessoa, A. King, F. de Moliner, M. Vendrell, et al, “On the Synthesis of Quinone-Based BODIPY Hybrids: New Insights on Antitumor Activity and Mechanism of Action in Cancer Cells,” Bioorganic & Medicinal Chemistry Letters 27, no. 18 (2017): 4446–56. doi:10.1016/j.bmcl.2017.08.007.
  • H. Z. Zhang, Z. L. Zhao, and C. H. Zhou, " “Recent Advance in Oxazole-Based Medicinal Chemistry,” European Journal of Medicinal Chemistry 144 (2018): 444–92. doi:10.1016/j.ejmech.2017.12.044.
  • N. Agrawal, and P. Mishra, “The Synthetic and Therapeutic Expedition of Isoxazole and Its Analogs,” Medicinal Chemistry Research: An International Journal for Rapid Communications on Design and Mechanisms of Action of Biologically Active Agents 27, no. 5 (2018): 1309–44. doi:10.1007/s00044-018-2152-6.
  • J. Zhu, J. Mo, H. Zhi Lin, Y. Chen, and H. Peng. Sun, “The Recent Progress of Isoxazole in Medicinal Chemistry,” Bioorganic & Medicinal Chemistry 26, no. 12 (2018): 3065–75. (doi:10.1016/j.bmc.2018.05.013.
  • M. Zia, S. Hameed, I. Ahmad, N. Tabassum, and S. Yousuf, “Regio-Isomeric Isoxazole Sulfonates: Synthesis, Characterization, Electrochemical Studies and DNA Binding Activity,” Journal of Molecular Structure 1220 (2020): 128635. doi:10.1016/j.molstruc.2020.128635.
  • S. T. Reddy, J. J. Mendonza, V. K. K. Makani, M. P. Bhadra, and V. M. Uppuluri, " “Synthesis of Some Novel Methyl β-Orsellinate Based 3, 5-Disubstituted Isoxazoles and Their anti-Proliferative Activity: Identification of Potent Leads Active against MCF-7 Breast Cancer Cell,” Bioorganic Chemistry 105 (2020): 104374. doi:10.1016/j.bioorg.2020.104374.
  • T. D. Bhatt, D. G. Gojiya, P. L. Kalavadiya, and H. S. Joshi, “Rapid, Greener and Ultrasound Irradiated One-Pot Synthesis of 4-(Substituted-1H-Pyrazol-4-yl)Methylene)-3-Isopropylisoxazol-5(4H)-Ones and Their In Vitro Anticancer Activity,” ChemistrySelect 4, no. 37 (2019): 11125–9. doi:10.1002/slct.201902164.
  • S. Ravula, R. R. Bobbala, and B. Kolli, “Synthesis of Novel Isoxazole Functionalized Pyrazolo[3,4‐b]Pyridine Derivatives; Their Anticancer Activity,” Journal of Heterocyclic Chemistry 57, no. 6 (2020): 2535–8. doi:10.1002/jhet.3968.
  • E. T. Warda, I. A. Shehata, M. B. El-Ashmawy, and N. S. El-Gohary, “New Series of Isoxazole Derivatives Targeting EGFR-TK: Synthesis, Molecular Modeling and Antitumor Evaluation,” Bioorganic & Medicinal Chemistry 28, no. 21 (2020): 115674. doi:10.1016/j.bmc.2020.115674.
  • A. Naouri, A. Djemoui, M. R. Ouahrani, M. B. Lahrech, N. Lemouari, D. H. A. Rocha, H. Albuquerque, R. F. Mendes, F. A. Almeida Paz, L. A. Helguero, et al, “Multicomponent and 1,3-Dipolar Cycloaddition Synthesis of Triazole- and Isoxazole-Acridinedione/Xanthenedione Heterocyclic Hybrids: Cytotoxic Effects on Human Cancer Cells,” Journal of Molecular Structure 1217 (2020): 128325. doi:10.1016/j.molstruc.2020.128325.
  • R. M. Mohareb, K. M. H. Hilmy, and Y. A. Elshehawy, “Discovery of New Thiophene, Pyrazole, Isoxazole Derivatives as Antitumor, c-Met, Tyrosine Kinase and Pim-1 Kinase Inhibitors,” Bulletin of the Chemical Society of Ethiopia 32, no. 2 (2018): 285–308. doi:10.4314/bcse.v32i2.9.
  • R. M. Mohareb, F. M. Manhi, M. A. A. Mahmoud, and A. Abdelwahab, “Uses of Dimedone to Synthesis Pyrazole, Isoxazole and Thiophene Derivatives with Antiproliferative, Tyrosine Kinase and Pim-1 Kinase Inhibitions,” Medicinal Chemistry Research 29, no. 8 (2020): 1536–51. doi:10.1007/s00044-020-02579-4.
  • M. A. Barmade, P. R. Murumkar, M. K. Sharma, and M. R. Yadav, “Medicinal Chemistry Perspective of Fused Isoxazole Derivatives,” Current Topics in Medicinal Chemistry 16, no. 26 (2016): 2863–83. doi:10.2174/1568026616666160506145700.
  • Raquib Alam, Divya Wahi, Raja Singh, Devapriya Sinha, Vibha Tandon, and Abhinav Grover, “Design, Synthesis, Cytotoxicity, HuTopoIIα Inhibitory Activity and Molecular Docking Studies of Pyrazole Derivatives as Potential Anticancer Agents,” Bioorganic Chemistry 69 (2016): 77–90. doi:10.1016/j.bioorg.2016.10.001.
  • D. A. Al-Turki, M. A. Al-Omar, L. A. Abou-Zeid, I. A. Shehata, and M. S. Al-Awady, “Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel Diaryl Heterocyclic Analogs as Potential Selective Cyclooxygenase-2 (COX-2) Inhibitors,” Saudi Pharmaceutical Journal : SPJ : The Official Publication of the Saudi Pharmaceutical Society 25, no. 1 (2017): 59–69. doi:10.1016/j.jsps.2015.07.001.
  • A. Kamal, A. B. Shaik, B. B. Rao, I. Khan, G. Bharath Kumar, and N. Jain, “Design and Synthesis of Pyrazole/Isoxazole Linked Arylcinnamides as Tubulin Polymerization Inhibitors and Potential Antiproliferative Agents,” Organic & Biomolecular Chemistry 13, no. 40 (2015): 10162–78. doi:10.1039/c5ob01257k.
  • K. S. Rakesh, S. Jagadish, K. S. Balaji, F. Zameer, T. R. Swaroop, C. D. Mohan, S. Jayarama, and K. S. Rangappa, “3,5-Disubstituted Isoxazole Derivatives: Potential Inhibitors of Inflammation and Cancer,” Inflammation 39, no. 1 (2016): 269–80. doi:10.1007/s10753-015-0247-5.
  • C. Sobolewski, C. Cerella, M. Dicato, L. Ghibelli, and M. Diederich, “The Role of Cyclooxygenase-2 in Cell Proliferation and Cell Death in Human Malignancies,” International Journal of Cell Biology 2010 (2010): 215158. doi:10.1155/2010/215158.
  • B. Liu, L. Qu, and S. Yan, “Cyclooxygenase-2 Promotes Tumor Growth and Suppresses Tumor Immunity,” Cancer Cell International 15 (2015): 106. doi:10.1186/s12935-015-0260-7.
  • Y. Tsuboi, T. Ichida, S. Sugitani, T. Genda, J. Inayoshi, M. Takamura, Y. Matsuda, M. Nomoto, and Y. Aoyagi, “Overexpression of Extracellular Signal-Regulated Protein Kinase and Its Correlation with Proliferation in Human Hepatocellular Carcinoma,” Liver International : official Journal of the International Association for the Study of the Liver 24, no. 5 (2004): 432–6. doi:10.1111/j.1478-3231.2004.0940.x.
  • B. Liang, S. Wang, X. Zhu, Y. Yu, Z. Cui, and Y. Yu, “Increased Expression of Mitogen-Activated Protein Kinase and Its Upstream Regulating Signal in Human Gastric Cancer,” World Journal of Gastroenterology 11, no. 5 (2005): 623–8. doi:10.3748/wjg.v11.i5.623.
  • M. Gagliardi, M. K. Pitner, J. Park, X. Xie, H. Saso, R. A. Larson, R. M. Sammons, H. Chen, Caimiao Wei, H. Masuda, et al, “Differential functions of ERK1 and ERK2 in lung metastasis processes in triple-negative breast cancer,” Scientific Reports 10, no. 1 (2020):s41598-020-65250-3. doi:10.1038/s41598-020-65250-3.
  • M. Yang, and C. Z. Huang, “Mitogen-Activated Protein Kinase Signaling Pathway and Invasion and Metastasis of Gastric Cancer,” World Journal of Gastroenterology 21, no. 41 (2015): 11673–9. doi:10.3748/wjg.v21.i41.11673.
  • A. K. Pullikuth, and A. D. Catling, “Scaffold Mediated Regulation of MAPK Signaling and Cytoskeletal Dynamics: A Perspective,” Cellular Signalling 19, no. 8 (2007): 1621–32. doi:10.1016/j.cellsig.2007.04.012.
  • R. Kalirajan, A. Pandiselvi, B. Gowramma, and P. Balachandran, “In-Silico Design, ADMET Screening, MM-GBSA Binding Free Energy of Some Novel Isoxazole Substituted 9-Anilinoacridines as HER2 Inhibitors Targeting Breast Cancer,” Current Drug Research Reviews 11, no. 2 (2019): 118–28. doi:10.2174/2589977511666190912154817.
  • A. Mangoni, J. Eynde, J. Jampilek, D. Hadjipavlou-Litina, H. Liu, J. Reynisson, M. Sousa, P. Gomes, K. Prokai-Tatrai, T. Tuccinardi, et al, “Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes–4,” Molecules 24, no. 13 (2019): 130. doi:10.3390/molecules24010130.
  • L. Scotti, F. Mendonça-Junior, and M. Scotti, “Editorial (Thematic Issue: Hybrid Compounds as Multitarget Agents in Medicinal Chemistry - Part II),” Current Topics in Medicinal Chemistry 17, no. 9 (2017): 957–8. doi:10.2174/156802661709170213205211.
  • H. A. Alzahrani, M. M. Alam, A. A. Elhenawy, A. M. Malebari, and S. Nazreen, “Synthesis, Antiproliferative, Docking and DFT Studies of Benzimidazole Derivatives as EGFR Inhibitors,” Journal of Molecular Structure 1253, no. 1253 (2022): 132265. doi:10.1016/j.molstruc.2021.132265.
  • M. M. Alam, “1,2,3-Triazole Hybrids as Anticancer Agents: A Review,” Archiv Der Pharmazie 355, no. 1 (2022): 2100158. doi:10.1002/ardp.202100158.
  • A. S. A. Almalki, S. Nazreen, A. M. Malebari, N. M. Ali, A. A. Elhenawy, A. A. A. Alghamdi, A. Ahmad, S. Y. M. Alfaifi, M. A. Alsharif, and M. M. Alam, “Synthesis and Biological Evaluation of 1,2,3-Triazole Tethered Thymol-1,3,4-Oxadiazole Derivatives as Anticancer and Antimicrobial Agents,” Pharmaceuticals 14, no. 9 (2021): 866– 18. doi:10.3390/ph14090866.
  • M. M. Alam, M. M. A. M. Malebari, N. Syed, T. Neamatallah, A. S. A. Almalki, A. A. Elhenawy, R. J. Obaid, and M. A. Alsharif, “Design, Synthesis and Molecular Docking Studies of Thymol Based 1,2,3-Triazole Hybrids as Thymidylate Synthase Inhibitors and Apoptosis Inducers against Breast Cancer Cells,” Bioorganic & Medicinal Chemistry 38, no. 38 (2021): 116136. doi:10.1016/j.bmc.2021.116136.
  • A. Borrelli, A. L. Tornesello, M. L. Tornesello, and F. M. Buonaguro, “Cell Penetrating Peptides as Molecular Carriers for anti-Cancer Agents,” Molecules 23, no. 2 (2018): 295. doi:10.3390/molecules23020295.
  • C. F. Albright, N. Graciani, W. Han, E. Yue, R. Stein, Z. Lai, M. Diamond, R. Dowling, L. Grimminger, S.-Y. Zhang, et al, “Matrix Metalloproteinase-Activated Doxorubicin Prodrugs Inhibit HT1080 Xenograft Growth Better than Doxorubicin with Less Toxicity,” Molecular Cancer Therapeutics 4, no. 5 (2005): 751–60. doi:10.1158/1535-7163.MCT-05-0006.
  • N. Dias, J. F. Goossens, B. Baldeyrou, A. Lansiaux, P. Colson, A. Di. Salvo, J. Bernal, A. Turnbull, D. J. Mincher, and C. Bailly, “Oxoazabenzo[de]Anthracenes Conjugated to Amino Acids: synthesis and Evaluation as DNA-Binding Antitumor Agents,” Bioconjugate Chemistry 16, no. 4 (2005): 949–58. doi:10.1021/bc050065x.
  • A. Molinari, A. Oliva, C. Ojeda, J. M. Miguel Del Corral, M. A. Castro, F. Mollinedo, and A. San Feliciano, “Synthesis and Evaluation as Antitumor Agents of 1,4-Naphthohydroquinone Derivatives Conjugated with Amino Acids and Purines,” Archiv Der Pharmazie 346, no. 12 (2013): 882–90. doi:10.1002/ardp.201300137.
  • A. Molinari, A. Oliva, M. Arismendi-Macuer, L. Guzmán, M. Fuentealba, M. Knox, R. Vinet, and A. San Feliciano, “New 1H-Benzo[f]Indazole-4,9-Diones Conjugated with C-Protected Amino Acids and Other Derivatives: Synthesis and In Vitro Antiproliferative Evaluation,” Molecules 20, no. 12 (2015): 21924–38. doi:10.3390/molecules201219809.
  • A. Molinari, A. Oliva, M. Arismendi-Macuer, L. Guzmán, W. Acevedo, D. Aguayo, R. Vinet, and A. San Feliciano, “Antiproliferative Benzoindazolequinones as Potential Cyclooxygenase-2 Inhibitors,” Molecules 24, no. 12 (2019): 2261. doi:10.3390/molecules24122261.
  • S. Sisodiya, P. Subarno, H. Chaudhary, P. Grewal, G. Kumar, D. P. Daniel, B. Das, D. Nayak, S. K. Guchhait, C. N. Kundu, et al, “Exploration of Benzo[b]Carbazole-6,11-Diones as Anticancer Agents: Synthesis and Studies of hTopoIIα Inhibition and Apoptotic Effects,” Bioorganic & Medicinal Chemistry Letters 49, no. 49 (2021): 128274. (2021) doi:10.1016/j.bmcl.2021.128274.
  • A. Molinari, A. Oliva, C. Ojeda, J. M. Miguel Del Corral, M. A. Castro, M. Faustino, and A. San Feliciano, “Synthesis and Evaluation as Antitumor Agents of 1,4-Naphthohydroquinone Derivatives Conjugated with Amino Acids and Purines,” Archiv Der Pharmazie 346, no. 12 (2013): 882–90. (2013) doi:10.1002/ardp.201300137.
  • T. Sander, J. Freyss, M. Von Kor, and C. Rufener, “DataWarrior: An Open-Source Program for Chemistry Aware Data Visualization and Analysis,” Journal of Chemical Information and Modeling 55, no. 2 (2015): 460–73. doi:10.1021/ci500588j.
  • C. A. Lipinski, F. Lombardo, B. W. Dominy, and P. J. Feeney, “Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings,” Advanced Drug Delivery Reviews 64 (2012): 4–17. doi:10.1016/j.addr.2012.09.019.
  • W. L. Jorgensen, and E. M. Duffy, “Prediction of Drug Solubility from Structure,” Advanced Drug Delivery Reviews 54, no. 3 (2002): 355–66. doi:10.1016/S0169-409X(02)00008-X.
  • H. M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T. N. Bhat, H. Weissig, I. N. Shindyalov, and P. E. Bourne, “The Protein Data Bank,” Nucleic Acids Research 28, no. 1 (2000): 235–42. doi:10.1107/S0907444902003451.
  • D. A. J. Ahmad, O. H. Negm, M. L. Alabdullah, S. Mirza, M. R. Hamed, V. Band, A. R. Green, I. O. Ellis, and E. A. Rakha, “Clinicopathological and Prognostic Significance of Mitogen-Activated Protein Kinases (MAPK) in Breast Cancers,” Breast Cancer Research and Treatment 159, no. 3 (2016): 457–67. doi:10.1007/s10549-016-3967-9.
  • A. R. Sepulveda, “Helicobacter, Inflammation, and Gastric Cancer,” Current Pathobiology Reports 1, no. 1 (2013): 9–18. doi:10.1007/s40139-013-0009-8.
  • O. Abdel-Rahman, “Targeting Vascular Endothelial Growth Factor (VEGF) Pathway in Gastric Cancer: Preclinical and Clinical Aspects,” Critical Reviews in Oncology/Hematology 93, no. 1 (2015): 18–27. doi:10.1016/j.critrevonc.2014.05.012.
  • P. Khanna, P. J. Chua, B. H. Bay, and G. H. Baeg, “The JAK/STAT Signaling Cascade in Gastric Carcinoma (Review),” International Journal of Oncology 47, no. 5 (2015): 1617–26. doi:10.3892/ijo.2015.3160.
  • C. Y. Xu, J. L. Guo, Z. N. Jiang, S. D. Xie, J. G. Shen, J. Y. Shen, and L. B. Wang, “Prognostic Role of Estrogen Receptor Alpha and Estrogen Receptor Beta in Gastric Cancer,” Annals of Surgical Oncology 17, no. 9 (2010): 2503–9. doi:10.1245/s10434-010-1031-2.
  • S. C. Hewitt, J. F. Couse, and K. S. Korach, “Estrogen Receptor Transcription and Transactivation: Estrogen Receptor Knockout Mice: what Their Phenotypes Reveal about Mechanisms of Estrogen Action,” Breast Cancer Research: BCR 2, no. 5 (2000): 345–52. doi:10.1186/bcr79.
  • O. Trott, and A. J. Olson, “AutoDock Vina: improving the Speed and Accuracy of Docking with a New Scoring Function, Efficient Optimization, and Multithreading,” Journal of Computational Chemistry 31, no. 2 (2010): 455–61. doi:10.1002/jcc.21334.
  • W. Humphrey, A. Dalke, and K. Schulten, “VMD: Visual Molecular Dynamics,” Journal of Molecular Graphics 14, no. 1 (1996): 33–8. doi:10.1016/0263-7855(96)00018-5.
  • A. C. Wallace, R. A. Laskowski, and J. M. Thornton, “LIGPLOT: A Program to Generate Schematic Diagrams of Protein-Ligand Interactions,” Protein Engineering 8, no. 2 (1995): 127–34. doi:10.1093/protein/8.2.127.
  • A. Molinari, A.Oliva, M. Arismendi, E. Imbarack, C. Gálvez, J. Maldonado, and A. S. Feliciano, “The Synthesis of Some Fused Pyrazolo-1,4-Naphthoquinones,” Journal of Heterocyclic Chemistry 52, no. 2 (2015): 620–2. doi:10.1002/jhet.2082.
  • P. L. Gaikwad, P. S. Gandhi, D. M. Jagdale, and V. J. Kadam, “The Use of Bioisosterism in Drug Design and Molecular Modification” American Journal of PharmTech Research 2, no. 24 (2012):1–23
  • X. Zhang, B. Li, M. Song, and J. Song, “Expression and Significance of ERK Protein in Human Breast Carcinoma,” Chinese Journal of Cancer Research 16, no. 4 (2004): 269–73. doi:10.1007/s11670-004-0041-7.
  • B. Singh, J. Berry, A. Shoher, V. Ramakrishnan, and A. Lucci, “Cox-2 overexpression increases motility and invasion of breast cancer cells,” Annals of Surgical Oncology 26, no. 5 (2005):1393-9. doi:10.1007/BF02523970.
  • J. Ma, L. Qin, and X. Li, “Role of STAT3 Signaling Pathway in Breast Cancer,” Cell Communication and Signaling: CCS 18, no. 1 (2020): 33. doi:10.1186/s12964-020-0527-z.
  • M. Hale, J. Janetka, F. Maltais, J. Cao, and R. Mashal, “Izoxazoles and Its Use as Inhibitors of the ERK,” (Patent ES2269458T3, filed September 5, 2001, and issued June 11, 2003).
  • C. Peifer, M. Abadleh, J. Bischof, D. Hauser, V. Schattel, H. Hirner, U. Knippschild, and S. Laufer, “3,4-Diaryl-Isoxazoles and -Imidazoles as Potent Dual Inhibitors of p38alpha Mitogen Activated Protein Kinase and Casein Kinase 1delta,” Journal of Medicinal Chemistry 52, no. 23 (2009): 7618–30. doi:10.1021/jm9005127.
  • S. A. Laufer, S. Margutti, and M. D. Fritz, “Substituted Isoxazoles as Potent Inhibitors of p38 MAP Kinase,” Chemmedchem. 1, no. 2 (2006): 197–207. doi:10.1002/cmdc.200500025.
  • A. Zarghi, and S. Arfaei, “Selective COX-2 Inhibitors: A Review of Their Structure-Activity Relationships,” Iranian Journal of Pharmaceutical Research: IJPR 10, no. 4 (2011): 655–83.
  • M. Peng, J. Deng, S. Zhou, D. Xiao, J. Long, N. Zhang, C. He, M. Mo, and X. Yang, “Dual Inhibition of Pirarubicin-Induced AKT and ERK Activations by Phenformin Sensitively Suppresses Bladder Cancer Growth,” Frontiers in Pharmacology 10 (2019): 1159. doi:10.3389/fphar.2019.01159.
  • Y. F. Chen, C. H. Chang, Z. N. Huang, Y. C. Su, S. J. Chang, and J. S. Jan, “The JAK Inhibitor Antcin H Exhibits Direct Anticancer Activity While Enhancing Chemotherapy against LMP1-Expressed Lymphoma,” Leukemia & Lymphoma 60, no. 5 (2019): 1193–203. doi:10.1080/10428194.2018.1512709.
  • E. Martinelli, T. Troiani, E. D'Aiuto, F. Morgillo, D. Vitagliano, A. Capasso, S. Costantino, L. P. Ciuffreda, F. Merolla, L. Vecchione, et al, “Antitumor Activity of Pimasertib, a Selective MEK 1/2 Inhibitor, in Combination with PI3K/mTOR Inhibitors or with Multi-Targeted Kinase Inhibitors in Pimasertib-Resistant Human Lung and Colorectal Cancer Cells,” International Journal of Cancer 133, no. 9 (2013): 2089–101. doi:10.1002/ijc.28236.
  • Á. P. Hernández, P. Chamorro, M. L. Rodríguez, J. M. Miguel Del Corral, P. A. García, A. Francesch, A. San Feliciano, and M. A. Castro, “New Antineoplastic Naphthohydroquinones Attached to Labdane and Rearranged Diterpene Skeletons,” Molecules 26, no. 2 (2021): 474. doi:10.3390/molecules26020474.

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