Novel pyrano[2,3-c]pyrazolopyrimidines as promising anticancer agents: Design, synthesis, and cell cycle arrest of HepG2 cells at S phase

References

• Derabli, C.; Boualia, I.; Abdelwahab, A. B.; Boulcina, R.; Bensouici, C.; Kirsch, G.; Debache, A. A Cascade Synthesis, in Vitro Cholinesterases Inhibitory Activity and Docking Studies of Novel Tacrine-Pyranopyrazole Derivatives. Bioorg. Med. Chem. Lett. 2018, 28, 2481–2484. DOI:10.1016/j.bmcl.2018.05.063.
   PubMed Web of Science ®Google Scholar
• Gameiro, I.; Michalska, P.; Tenti, G.; Cores, Á.; Buendia, I.; Rojo, A. I.; Georgakopoulos, N. D.; Hernández-Guijo, J. M.; Teresa Ramos, M.; Wells, G.; et al. Discovery of the First Dual GSK3β Inhibitor/Nrf2 Inducer. A New Multitarget Therapeutic Strategy for Alzheimer’s Disease. Sci. Rep. 2017, 7, 45701. DOI:10.1038/srep45701.
   PubMed Web of Science ®Google Scholar
• Bakherad, M.; Keivanloo, A.; Gholizadeh, M.; Doosti, R.; Javanmardi, M. Using Magnetized Water as a Solvent for a Green, Catalyst-Free, and Efficient Protocol for the Synthesis of Pyrano [2, 3-c] Pyrazoles and Pyrano [4′, 3′: 5, 6] Pyrazolo [2, 3-d]Pyrimidines. Res. Chem. Intermed. 2017, 43, 1013–1029. DOI:10.1007/s11164-016-2680-y.
   Web of Science ®Google Scholar
• Mandour, A.; El-Sawy, E.; Ebaid, M.; Hassan, S. Synthesis and Potential Biological Activity of Some Novel 3-[(N-Substituted Indol-3-yl) Methylene Amino]-6-Amino-4-Aryl-Pyrano (2, 3-c) Pyrazole-5-Carbonitriles and 3, 6-Diamino-4-(N-Substitutedindol-3-yl) Pyrano (2, 3-c) Pyrazole-5-Carbonitriles. Acta Pharm. 2012, 62, 15–30. DOI:10.2478/v10007-012-0007-0.
   PubMed Web of Science ®Google Scholar
• Thumar, N. J.; Patel, M. P. Synthesis and in Vitro Antimicrobial Evaluation of 4Hpyrazolopyran,-Benzopyran and Naphthopyran Derivatives of 1H-Pyrazole. Arkivoc 2010, 2009, 363–380. DOI:10.3998/ark.5550190.0010.d30.
   Google Scholar
• Abdelrazek, F. M.; Metz, P.; Metwally, N. H.; El-Mahrouky, S. F. Synthesis and Molluscicidal Activity of New Cinnoline and Pyrano [2, 3-c] Pyrazole Derivatives. Arch. Pharm. (Weinheim) 2006, 339, 456–460. DOI:10.1002/ardp.200600057.
   PubMed Web of Science ®Google Scholar
• Zaki, M. E.; Soliman, H. A.; Hiekal, O. A.; Rashad, A. E. Pyrazolopyranopyrimidines as a Class of Anti-Inflammatory Agents. Z Naturforsch. C J. Biosci. 2006, 61, 1–5. DOI:10.1515/znc-2006-1-201.
   PubMed Web of Science ®Google Scholar
• Foloppe, N.; Fisher, L. M.; Howes, R.; Potter, A.; Robertson, A. G.; Surgenor, A. E. Identification of Chemically Diverse Chk1 Inhibitors by Receptor-Based Virtual Screening. Bioorg. Med. Chem. 2006, 14, 4792–4802. DOI:10.1016/j.bmc.2006.03.021.
   Google Scholar
• Saravana Mani, K.; Rajendran, S. P. L-Proline Catalyzed Three Component Synthesis of Pyrano [2,3-c] Pyrazole-5-Carbonitrile Derivatives and in Vitro Antimalarial Evaluation. Synth. Commun. 2017, 47, 2036–2043. DOI:10.1080/00397911.2017.1362437.
   Web of Science ®Google Scholar
• Yang, X.-H.; Zhang, P.-H.; Wang, Z.-M.; Jing, F.; Zhou, Y.-H.; Hu, L.-H. Synthesis and Bioactivity of Lignin Related High-Added-Value 2H, 4H-Dihydro-Pyrano [2, 3-c]Pyrazoles and 1H, 4H-Dihydro-Pyrano [2, 3-c] Pyrazoles. Ind. Crops Prod. 2014, 52, 413–419. DOI:10.1016/j.indcrop.2013.11.017.
   Web of Science ®Google Scholar
• Bejjanki, N. K.; Venkatesham, A.; Madda, J.; Kommu, N.; Pombala, S.; Kumar, C. G.; Prasad, K. R.; Nanubolu, J. B. Synthesis of New Chromeno-Annulated Cis-Fused Pyrano[4, 3-c] Isoxazole Derivatives via Intramolecular Nitrone Cycloaddition and Their Cytotoxicity Evaluation. Bioorg. Med. Chem. Lett. 2013, 23, 4061–4066. DOI:10.1016/j.bmcl.2013.05.060.
   PubMed Web of Science ®Google Scholar
• Mecadon, H.; Rohman, M. R.; Kharbangar, I.; Laloo, B. M.; Kharkongor, I.; Rajbangshi, M.; Myrboh, B. L-Proline as an Efficient Catalyst for the Multicomponent Synthesis of 6-Amino-4-Alkyl/Aryl-3-Methyl-2, 4-Dihydropyrano [2, 3-c]Pyrazole-5-Carbonitriles in Water. Tetrahedron Lett. 2011, 52, 3228–3231. DOI:10.1016/j.tetlet.2011.04.048.
   Web of Science ®Google Scholar
• Thanh, N. D.; Hai, D. S.; Ha, N. T. T.; Tung, D. T.; Le, C. T.; Van, H. T. K.; Toan, V. N.; Toan, D. N.; Dang, L. H. Synthesis, Biological Evaluation and Molecular Docking Study of 1,2,3-1H-Triazoles Having 4H-Pyrano[2,3-d]Pyrimidine as Potential Mycobacterium tuberculosis Protein Tyrosine Phosphatase B Inhibitors. Bioorg. Med. Chem. Lett. 2019, 29, 164–171. DOI:10.1016/j.bmcl.2018.12.009.
   PubMed Web of Science ®Google Scholar
• Chabchoub, F.; Messaâd, M.; Mansour, H. B.; Chekir-Ghedira, L.; Salem, M. Synthesis and Antigenotoxic Activity of Some Naphtho[2,1-b]Pyrano[3,2-e][1,2,4]Triazolo[1,5-c]Pyrimidine Derivatives. Eur. J. Med. Chem. 2007, 42, 715–718. DOI:10.1016/j.ejmech.2006.12.002.
   PubMed Web of Science ®Google Scholar
• Poola, S.; Shaik, M. S.; Sudileti, M.; Yakkate, S.; Nalluri, V.; Chippada, A.; Cirandur, S. R. Nano CuO–Ag-Catalyzed Synthesis of Some Novel Pyrano[2,3-d] Pyrimidine Derivatives and Evaluation of Their Bioactivity. J. Chin. Chem. Soc. 2019, 67, 805–820. DOI:10.1002/jccs.201900256.
   Web of Science ®Google Scholar
• Hekal, M. H.; Farag, P. S.; Hemdan, M. M.; El-Sayed, W. M. New N-(1,3,4-Thiadiazol-2-yl)Furan-2-Carboxamide Derivatives as Potential Inhibitors of the VEGFR-2. Bioorg. Chem. 2021, 115, 105176. DOI:10.1016/j.bioorg.2021.105176.
   PubMed Web of Science ®Google Scholar
• Hekal, M. H.; El-Naggar, A. M.; Abu El-Azm, F. S. M..; El-Sayed, W. M.. Synthesis of New Oxadiazol-Phthalazin Derivatives with Anti-Proliferative Activity; Molecular Docking, pro-Apoptotic, and Enzyme Inhibition Profile. RSC Adv. 2020, 10, 3675–3688. DOI:10.1039/c9ra09016a.
   PubMed Web of Science ®Google Scholar
• El-Metwally, S. A.; Khalil, A. K.; El-Sayed, W. M. Design, Molecular Modeling and Anticancer Evaluation of Thieno[2,3-d]Pyrimidine Derivatives as Inhibitors of Topoisomerase II. Bioorg. Chem. 2020, 94, 103492. DOI:10.1016/j.bioorg.2019.103492.
   PubMed Web of Science ®Google Scholar
• Ismail, M. A.; Negm, A.; Arafa, R. K.; Abdel-Latif, E.; El-Sayed, W. M. Anticancer Activity, Dual Prooxidant/Antioxidant Effect and Apoptosis Induction Profile of New Bichalcophene-5-Carboxamidines. Eur. J. Med. Chem. 2019, 169, 76–88. DOI:10.1016/j.ejmech.2019.02.062.
   PubMed Web of Science ®Google Scholar
• Salem, M. S.; Hussein, R. A.; El-Sayed, W. M. Substitution at Phenyl Rings of Chalcone and Schiff Base Moieties Accounts for Their Antiproliferative Activity. Anticancer. Agent Med. Chem. 2019, 19, 620–626. DOI:10.2174/1871520619666190225122338.
   PubMed Web of Science ®Google Scholar
• Hussin, W. A.; Ismail, M. A.; Alzahrani, A. M.; El-Sayed, W. M. Evaluation of the Biological Activity of Novel Monocationic Fluoroaryl-2,2’-Bichalcophenes and Their Analogues. Drug Design. Devel. Ther 2014, 8, 963–972. DOI:10.2147/DDDT.S66469.
   PubMed Web of Science ®Google Scholar
• Hekal, M. H.; Samir, S. S.; Ali, Y. M.; El-Sayed, W. M. New Benzochromeno[2,3-d]Pyrimidines and Benzochromenotriazolo[1,5-c]Pyrimidines as Potential Inhibitors of Topoisomerase II. Polycyclic Aromat. Compd. 2022, 42, 7644–7660. DOI:10.1080/10406638.2021.2006247.
   Web of Science ®Google Scholar
• El-Naggar, A. M.; Khalil, A. K.; Zeidan, H. M.; El-Sayed, W. M. Eco-Friendly Synthesis of Pyrido[2,3-d]Pyrimidine Analogs and Their Anticancer and Tyrosine Kinase Inhibition Activities. Anti-Cancer Agents Med. Chem 2017, 17, 1644–1651.
   PubMed Web of Science ®Google Scholar
• Franklin, M. R.; Moos, P. J.; El-Sayed, W. M.; Aboul-Fadl, T.; Roberts, J. C. Pre- and Post-Initiation Chemoprevention Activity of 2-Alkyl/Aryl Selenazolidine-4(R)-Carboxylic Acids Against Tobacco-Derived Nitrosamine (NNK)-Induced Lung Tumors in the a/J Mouse. Chem Biol Interact 2007, 168, 211–220. DOI:10.1016/j.cbi.2007.04.012.
   PubMed Web of Science ®Google Scholar
• El-Sayed, W. M.; Hussin, W. M.; Mahmoud, A. A.; AlFredan, M. A. The Conyza Triloba Extracts with High Chlorophyll Content and Free Radical Scavenging Activity Had Anticancer Activity in Cell Lines. Biomed Res. Int. 2013, 2013, 945638–945611. DOI:10.1155/2013/945638.
   PubMed Web of Science ®Google Scholar
• Wang, Y.; Fisher, J. C.; Mathew, R.; Ou, L.; Otieno, S.; Sublet, J. Intrinsic Disorder Mediates the Diverse Regulatory Functions of the Cdk Inhibitor p21. Nat. Chem. Biol. 2011, 7, 214–221. DOI:10.1038/nchembio.536.
   PubMed Web of Science ®Google Scholar
• Abbas, T.; Dutta, A. p21 in Cancer: Intricate Networks and Multiple Activities. Nat. Rev. Cancer 2009, 9, 400–414. DOI:10.1038/nrc2657.
   PubMed Web of Science ®Google Scholar
• Karimian, A.; Ahmadi, Y.; Yousefi, B. Multiple Functions of p21 in Cell Cycle, Apoptosis and Transcriptional Regulation after DNA Damage. DNA Repair 2016, 42, 63–71. DOI:10.1016/j.dnarep.2016.04.008.
   PubMed Web of Science ®Google Scholar
• Abdelgawad, N. H.; Ismail, M. F.; Hekal, M. H.; Marzouk, M. I. Design, Synthesis, and Evaluation of Some Novel Heterocycles Bearing Pyrazole Moiety as Potential Anticancer Agents. J. Heterocyclic Chem. 2019, 56, 1771–1779. DOI:10.1002/jhet.3544.
   Web of Science ®Google Scholar
• (a) Mahmoud, M. R.; Abou-Elmagd, W. S. I.; Derbala, H.A.; Hekal, M. H. Novel Synthesis of Some Phthalazinone Derivatives. Chin. J. Chem. 2011, 29, 1446–1450;
   Web of Science ®Google Scholar
  (b) Ali, A. T.; Hekal, M. H. Convenient Synthesis and anti-Proliferative Activity of Some Benzochromenes and Chromenotriazolopyrimidines under Classical Methods and Phase Transfer Catalysis. Synth. Commun. 2019, 49, 3498–3509.
   Web of Science ®Google Scholar
  (c) Hekal, M. H.; Abu El-Azm, F. S. M.; Samir S. S., An Efficient Approach for the Synthesis and Antimicrobial Evaluation of Some New Benzocoumarins and Related Compounds. Synth. Commun. 2021, 51, 2175–2186 DOI:10.1002/cjoc.201180264.
   Web of Science ®Google Scholar
• (a) Mahmoud, M. R.; Abu El-Azm, F. S. M.; Ismail, M. F.; Hekal, M. H.; Ali, Y. M. Synthesis and Antitumor Evaluation of Novel Tetrahydrobenzo[4/,5/]Thieno[3/,2/:5,6]Pyrimido[1,2-b]Isoquinoline Derivatives. Synth. Commun. 2018, 48, 428–438;
   Web of Science ®Google Scholar
  (b) Hekal M. H.; Abu El-Azm, F. S. M.; Sallam, H. A. Synthesis, Spectral Characterization, and in Vitro Biological Evaluation of Some Novel Isoquinolinone-Based Heterocycles as Potential Antitumor Agents. J. Het. Chem. 2019, 56, 795–803. DOI:10.1080/00397911.2017.1406520.
   Web of Science ®Google Scholar
• Atta-Allah, S. R.; Gouhar, R. S.; Hemdan, M. M.; Abou-Elmagd, W. S. I.; Haneen, D. S. A.; Kandeel, K. A. A.; A. S. A., Youssef. Synthesis and Antitumor Activity Evaluation of Some Novel Pyrazolotriazine Derivatives. Synth. Commun 2017, 47, 299–309. DOI:10.1080/00397911.2016.1262422.
   Web of Science ®Google Scholar
• Gouhar, R. S.; Haneen, D. S. A.; El-Hallouty, S. M. Synthesis and Anticancer Evaluation of Some Novel Quinazolin-4(3H)-One Derivatives. J. Heterocyclic Chem. 2019, 56, 1651–1660. DOI:10.1002/jhet.3559.
   Web of Science ®Google Scholar
• (a) Youssef, A. S. A.; Kandeel, K. A.; Abou-Elmagd, W. S. I.; Haneen, D. S. A. Synthesis of Novel Heterocycles Derived from 4-Arylmethylene-2-Phenyl-1,3-Oxazole-5(4H)-Ones. J. Heterocyclic Chem., 2016, 53(5), 809–816;
   Google Scholar
  (b) Alkhatib, M. M.; Abdalha, A. A.; Samir, S. S.; Youssef, A. S., Abou-Elmagd, W. S. I.; Haneen, D. S. A. An Efficient Synthesis of Some Newly Anthracene Derivatives Having Effective Insecticidal Activity. Synth. Commun. 2022, 52, 1368–1378. DOI:10.1002/jhet.2329.
   Web of Science ®Google Scholar
• Gad, N. M.; Abou-Elmagd, W. S.; Haneen, D. S.; Ramadan, S. K. Reactivity of 5-Phenyl-3-[(2-Chloroquinolin-3-yl) Methylene] Furan-2 (3H)-One towards Hydrazine and Benzylamine: A Comparative Study. Synth. Commun. 2021, 51, 1384–1397. DOI:10.1080/00397911.2021.1882498.
   Web of Science ®Google Scholar
• Kaboudin, B.; Khodamorady, M.; Abedi, Y. A Practical and Convenient Method for the Synthesis of Some Benzimidazoles. Org. Prep. Proced. Int. 2013, 45, 162–167. DOI:10.1080/00304948.2013.765294.
   Google Scholar
• Skehan, P.; Storeng, R.; Scudiero, D.; Monks, A.; McMahon, J.; Vistica, D.; Warren, J. T.; Bokesch, H.; Kenney, S.; Boyd, M. R. New Colorimetric Cytotoxicity Assay for Anticancer-Drug Screening. J. Natl. Cancer Inst. 1990, 82, 1107–1112. DOI:10.1093/jnci/82.13.1107.
   PubMed Web of Science ®Google Scholar
• Saleh, N. M.; El-Gazzar, M. G.; Aly, H. M.; Othman, R. A. Novel Anticancer Fused Pyrazole Derivatives as EGFR and VEGFR-2 Dual TK Inhibitors. Front. Chem. 2019, 7, 917. DOI:10.3389/fchem.2019.00917.
   PubMed Web of Science ®Google Scholar
• Nassar, I. F.; Abdel Aal, M. T.; El-Sayed, W. A.; A E Shahin, M.; Elsakka, E. G. E.; Mokhtar, M. M.; Hegazy, M.; Hagras, M.; Mandour, A. A.; Ismail, N. S. M. Discovery of Pyrazolo [3, 4-d] Pyrimidine and Pyrazolo [4, 3-e][1, 2, 4] Triazolo [1, 5-c] Pyrimidine Derivatives as Novel CDK2 Inhibitors: synthesis, Biological and Molecular Modeling Investigations. RSC Adv. 2022, 12, 14865–14882. DOI:10.1039/d2ra01968j.
   PubMed Web of Science ®Google Scholar
• Shapiro, G. I.; Harper, J. W. Anticancer Drug Targets: cell Cycle and Checkpoint Control. J. Clin. Invest. 1999, 104, 1645–1653. DOI:10.1172/JCI9054.
   PubMed Web of Science ®Google Scholar
• Toogood, P. L. Progress toward the Development of Agents to Modulate the Cell Cycle. Curr. Opin. Chem. Biol. 2002, 6, 472–478. DOI:10.1016/s1367-5931(02)00342-3.
   PubMed Web of Science ®Google Scholar
• Zhu, H.; Zhang, L.; Wu, S.; Teraishi, F.; Davis, J. J.; Jacob, D.; Fang, B. Induction of S-Phase Arrest and p21 Overexpression by a Small Molecule 2[[3-(2,3-Dichlorophenoxy)Propyl] Amino]Ethanol in Correlation with Activation of ERK. Oncogene 2004, 23, 4984–4992. DOI:10.1038/sj.onc.1207645.
   PubMed Web of Science ®Google Scholar
• Porter, A. G.; Jänicke, R. U. Emerging Roles of Caspase-3 in Apoptosis. Cell Death Differ. 1999, 6, 99–104. DOI:10.1038/sj.cdd.4400476.
   PubMed Web of Science ®Google Scholar
• Bertoli, C.; Skotheim, J. M.; de Bruin, R. A. M. Control of Cell Cycle Transcription During G1 and S Phases. Nat. Rev. Mol. Cell Biol. 2013, 14, 518–528. DOI:10.1038/nrm3629.
   PubMed Web of Science ®Google Scholar
• Gartel, A. L.; Tyner, A. L. The Role of the Cyclin-Dependent Kinase Inhibitor p21 in Apoptosis. Mol. Cancer Ther. 2002, 1, 639–649.
   PubMed Web of Science ®Google Scholar
• Harper, J. W.; Adami, G. R.; Wei, N.; Keyomarsi, K.; Elledge, S. J. The p21 Cdk-Interacting Protein Cip1 is a Potent Inhibitor of G1 Cyclin-Dependent Kinases. Cell 1993, 75, 805–816. DOI:10.1016/0092-8674(93)90499-G.
   PubMed Web of Science ®Google Scholar
• Lee, Y. R.; Park, S. Y. P53 Expression in Hepatocellular Carcinoma: Influence on the Radiotherapeutic Response of the Hepatocellular Carcinoma. Clin. Mol. Hepatol. 2015, 21, 230–231. DOI:10.3350/cmh.2015.21.3.230.
   PubMedGoogle Scholar
• Lee, S.; Helfman, D. M. Cytoplasmic p21Cip1 is Involved in Ras-Induced Inhibition of the ROCK/LIMK/Cofilin Pathway. J. Biol. Chem. 2004, 279, 1885–1891. DOI:10.1074/jbc.M306968200.
   PubMed Web of Science ®Google Scholar
• Bouchet, B. P.; Fauvet, F.; Grelier, G.; Galmarini, C. M.; Puisieux, A. p21(Cip1) Regulates Cell-Substrate Adhesion and Interphase Microtubule Dynamics in Untransformed Human Mammary Epithelial Cells. Eur. J. Cell Biol. 2011, 90, 631–641. DOI:10.1016/j.ejcb.2011.03.002.
   PubMed Web of Science ®Google Scholar
• (a) Guo, R. Y.; An, Z. M.; Mo, L. P.; Yang, S. T.; Liu, H. X.; Wang, S. X.; Zhang, Z. H. Meglumine Promoted One-Pot, Four-Component Synthesis of Pyranopyrazole Derivatives. Tetrahedron, 2013, 69(47), 9931–9938;
   Web of Science ®Google Scholar
  (b) Kamel, M. M. Convenient Synthesis, Characterization, Cytotoxicity and Toxicity of Pyrazole Derivatives. Acta Chim. Sloven. 2015, 62(1), 136–152. DOI:10.1016/j.tet.2013.09.082.
   PubMed Web of Science ®Google Scholar
• Hafez, H. N.; El-Gazzar, A. R. Synthesis of Pyranopyrazolo N-Glycoside and Pyrazolopyranopyrimidine C-Glycoside Derivatives as Promising Antitumor and Antimicrobial Agents. Acta Pharm. 2015, 65, 215–233. DOI:10.1515/acph-2015-0022.
   PubMed Web of Science ®Google Scholar
• Al-Shun, S. A.; El-Senduny, F. F.; Ismail, M. A.; El-Sayed, W. M.; Badria, F. A.; Youssef, M. M. Anticancer Activity of New Cationic Arylthiophenes against Hepatocellular Carcinoma. Life Sci. 2021, 269, 119028. DOI:10.1016/j.lfs.2021.119028.
   PubMed Web of Science ®Google Scholar
• Liang, C. C.; Park, A. Y.; Guan, J. L. In Vitro Scratch Assay: A Convenient and Inexpensive Method for Analysis of Cell Migration in Vitro. Nat. Protoc. 2007, 2, 329–333. DOI:10.1038/nprot.2007.30.
   PubMed Web of Science ®Google Scholar
• Elsibaei, S. M.; Amleh, A.; Ismail, M. A.; El-Sayed, W. M. Azafuramidines as Potential Anticancer Agents: Pro-Apoptotic Profile and Cell Cycle Arrest. Bioorg. Med. Chem. Lett. 2023, 97, 129550. DOI:10.1016/j.bmcl.2023.129550.
   PubMed Web of Science ®Google Scholar
• Hekal, M. H.; Farag, P. S.; Hemdan, M. M.; Sayed, A. A El.; Hassaballah, A. I.; Sayed, W. M. E. New 1,3,4-Thiadiazoles as Potential Anticancer Agents: Pro-Apoptotic, Cell Cycle Arrest, Molecular Modelling, and ADMET Profile. RSC Adv. 2023, 13, 15810–15825. DOI:10.1039/d3ra02716c.
   PubMed Web of Science ®Google Scholar
• Ismail, M. A.; Abdelwahab, G. A.; Hamama, W. S.; Abdel-Latif, E.; El-Senduny, F.; El-Sayed, W. M. Synthesis and Antiproliferative Activity of New Thienylnicotinamidines: Pro-Apoptotic Profile and Cell Cycle Arrest of HepG2 Cells. Arch. Pharm. (Weinheim) 2022, 355, e2100385. DOI:10.1002/ardp.202100385.
   PubMedGoogle Scholar