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Tetrahydroisoquinoline amide substituted phenyl pyrazoles as selective Bcl-2 inhibitors.

Porter J, Payne A, de Candole B, Ford D, Hutchinson B, Trevitt G, Turner J, Edwards C, Watkins C, Whitcombe I, Davis J, Stubberfield C
Bioorg Med Chem Lett 19 230-3 (2009)
Cited: 64 times
EuropePMC logo PMID: 19027294

Abstract

Anti-apoptotic Bcl-2 protects cells from apoptosis by binding to pro-apoptotic members of the Bcl-2 family thereby playing a role in tumour survival in response to chemo- or radiation therapy. We describe a series of phenyl pyrazoles that have high affinity for Bcl-2 and rationalise the observed SAR by means of an X-ray crystal structure.

Reviews - 2w3l mentioned but not cited (1)

  1. Friedelin: Structure, Biosynthesis, Extraction, and Its Potential Health Impact. Singh SK, Shrivastava S, Mishra AK, Kumar D, Pandey VK, Srivastava P, Pradhan B, Behera BC, Bahuguna A, Baek KH. Molecules 28 7760 (2023)

Articles - 2w3l mentioned but not cited (43)

  1. Fumigaclavine C from a marine-derived fungus Aspergillus fumigatus induces apoptosis in MCF-7 breast cancer cells. Li YX, Himaya SW, Dewapriya P, Zhang C, Kim SK. Mar Drugs 11 5063-5086 (2013)
  2. Strophanthidin Attenuates MAPK, PI3K/AKT/mTOR, and Wnt/β-Catenin Signaling Pathways in Human Cancers. Reddy D, Ghosh P, Kumavath R. Front Oncol 9 1469 (2019)
  3. Establishing Drug Discovery and Identification of Hit Series for the Anti-apoptotic Proteins, Bcl-2 and Mcl-1. Murray JB, Davidson J, Chen I, Davis B, Dokurno P, Graham CJ, Harris R, Jordan A, Matassova N, Pedder C, Ray S, Roughley SD, Smith J, Walmsley C, Wang Y, Whitehead N, Williamson DS, Casara P, Le Diguarher T, Hickman J, Stark J, Kotschy A, Geneste O, Hubbard RE. ACS Omega 4 8892-8906 (2019)
  4. Network Pharmacology-Based Strategy for the Investigation of the Anti-Obesity Effects of an Ethanolic Extract of Zanthoxylum bungeanum Maxim. Wang Y, Yang SH, Zhong K, Jiang T, Zhang M, Kwan HY, Su T. Front Pharmacol 11 572387 (2020)
  5. Alleviation of Memory Deficit by Bergenin via the Regulation of Reelin and Nrf-2/NF-κB Pathway in Transgenic Mouse Model. Shal B, Khan A, Khan AU, Ullah R, Ali G, Islam SU, Haq IU, Ali H, Seo EK, Khan S. Int J Mol Sci 22 6603 (2021)
  6. Highly precise protein-protein interaction prediction based on consensus between template-based and de novo docking methods. Ohue M, Matsuzaki Y, Shimoda T, Ishida T, Akiyama Y. BMC Proc 7 S6 (2013)
  7. FRAGSITE: A Fragment-Based Approach for Virtual Ligand Screening. Zhou H, Cao H, Skolnick J. J Chem Inf Model 61 2074-2089 (2021)
  8. Identification of Aloperine as an anti-apoptotic Bcl2 protein inhibitor in glioma cells. Xu Z, Wang X, Chen X, Zeng S, Qian L, Wei J, Gong Z, Yan Y. PeerJ 7 e7652 (2019)
  9. New 1,3,4-Thiadiazole Derivatives with Anticancer Activity. Janowska S, Khylyuk D, Bielawska A, Szymanowska A, Gornowicz A, Bielawski K, Noworól J, Mandziuk S, Wujec M. Molecules 27 1814 (2022)
  10. A bioinformatics investigation into the pharmacological mechanisms of the effect of the Yinchenhao decoction on hepatitis C based on network pharmacology. Zhang J, Liu X, Wu J, Zhou W, Tian J, Guo S, Jia SS, Meng Z, Ni M. BMC Complement Med Ther 20 50 (2020)
  11. Acetogenins from Annona muricata as potential inhibitors of antiapoptotic proteins: a molecular modeling study. Antony P, Vijayan R. Drug Des Devel Ther 10 1399-1410 (2016)
  12. Novel Nanocombinations of l-Tryptophan and l-Cysteine:  Preparation, Characterization, and Their Applications for Antimicrobial and Anticancer Activities. Abd-Elhamid AI, El-Gendi H, Abdallah AE, El-Fakharany EM. Pharmaceutics 13 1595 (2021)
  13. Synthesis, Molecular Docking Study, and Cytotoxic Activity against MCF Cells of New Thiazole-Thiophene Scaffolds. Gomha SM, Riyadh SM, Huwaimel B, Zayed MEM, Abdellattif MH. Molecules 27 4639 (2022)
  14. Synthesis, and docking studies of novel heterocycles incorporating the indazolylthiazole moiety as antimicrobial and anticancer agents. Dawoud NTA, El-Fakharany EM, Abdallah AE, El-Gendi H, Lotfy DR. Sci Rep 12 3424 (2022)
  15. In Silico Computational Studies of Bioactive Secondary Metabolites from Wedelia trilobata against Anti-Apoptotic B-Cell Lymphoma-2 (Bcl-2) Protein Associated with Cancer Cell Survival and Resistance. Gowtham HG, Ahmed F, Anandan S, Shivakumara CS, Bilagi A, Pradeep S, Shivamallu C, Shati AA, Alfaifi MY, Elbehairi SEI, Achar RR, Silina E, Stupin V, Murali M, Kollur SP. Molecules 28 1588 (2023)
  16. Antitumor effect of proanthocyanidin induced apoptosis in human colorectal cancer (HT-29) cells and its molecular docking studies. Suganya M, Gnanamangai BM, Ravindran B, Chang SW, Selvaraj A, Govindasamy C, Elsadek MF, Ponmurugan P. BMC Chem 13 21 (2019)
  17. Huang-Pu-Tong-Qiao Formula Ameliorates the Hippocampus Apoptosis in Diabetic Cognitive Dysfunction Mice by Activating CREB/BDNF/TrkB Signaling Pathway. Ye S, Xie DJ, Zhou P, Gao HW, Zhang MT, Chen DB, Qin YP, Lei X, Li XQ, Liu J, Cheng YX, Yao YC, Cai B, Shen GM. Evid Based Complement Alternat Med 2021 5514175 (2021)
  18. Novel Triterpenic Acid-Benzotriazole Esters Act as Pro-Apoptotic Antimelanoma Agents. Mioc M, Mioc A, Prodea A, Milan A, Balan-Porcarasu M, Racoviceanu R, Ghiulai R, Iovanescu G, Macasoi I, Draghici G, Dehelean C, Soica C. Int J Mol Sci 23 9992 (2022)
  19. Systematically Deciphering the Pharmacological Mechanism of Fructus Aurantii via Network Pharmacology. Jin Q, Lu J, Gao R, Xu J, Pan X, Wang L. Evid Based Complement Alternat Med 2021 6236135 (2021)
  20. Dr. PIAS 2.0: an update of a database of predicted druggable protein-protein interactions. Sugaya N, Kanai S, Furuya T. Database (Oxford) 2012 bas034 (2012)
  21. Jiawei Foshou San Induces Apoptosis in Ectopic Endometrium Based on Systems Pharmacology, Molecular Docking, and Experimental Evidence. Wei J, Zhao B, Zhang C, Shen B, Zhang Y, Li C, Chen Y. Evid Based Complement Alternat Med 2019 2360367 (2019)
  22. Lepidium sativum Secondary Metabolites (Essential Oils): In Vitro and In Silico Studies on Human Hepatocellular Carcinoma Cell Lines. Nazir S, El-Sherif AA, Abdel-Ghani NT, Ibrahim MAA, Hegazy MF, Atia MAM. Plants (Basel) 10 1863 (2021)
  23. Synthesis, Anticancer Assessment, and Molecular Docking of Novel Chalcone-Thienopyrimidine Derivatives in HepG2 and MCF-7 Cell Lines. Safwat GM, Hassanin KMA, Mohammed ET, Ahmed EK, Abdel Rheim MR, Ameen MA, Abdel-Aziz M, Gouda AM, Peluso I, Almeer R, Abdel-Daim MM, Abdel-Wahab A. Oxid Med Cell Longev 2021 4759821 (2021)
  24. Competition Between Phenothiazines and BH3 Peptide for the Binding Site of the Antiapoptotic BCL-2 Protein. do Carmo AL, Bettanin F, Oliveira Almeida M, Pantaleão SQ, Rodrigues T, Homem-de-Mello P, Honorio KM. Front Chem 8 235 (2020)
  25. Novel sulphonamide-bearing methoxyquinazolinone derivatives as anticancer and apoptosis inducers: synthesis, biological evaluation and in silico studies. Alqahtani AS, Ghorab MM, Nasr FA, Ahmed MZ, Al-Mishari AA, Attia SM. J Enzyme Inhib Med Chem 37 86-99 (2022)
  26. The Effects of Thymoquinone on Viability, and Anti-apoptotic Factors (BCL-XL, BCL-2, MCL-1) in Prostate Cancer (PC3) Cells: An In Vitro and Computer-Simulated Environment Study. Saffari Chaleshtori J, Heidari-Sureshjani E, Moradi F, Heidarian E. Adv Pharm Bull 9 490-496 (2019)
  27. 3-Pyridinylidene Derivatives of Chemically Modified Lupane and Ursane Triterpenes as Promising Anticancer Agents by Targeting Apoptosis. Kazakova O, Șoica C, Babaev M, Petrova A, Khusnutdinova E, Poptsov A, Macașoi I, Drăghici G, Avram Ș, Vlaia L, Mioc A, Mioc M, Dehelean C, Voicu A. Int J Mol Sci 22 10695 (2021)
  28. Chemosensing Properties of Coumarin Derivatives: Promising Agents with Diverse Pharmacological Properties, Docking and DFT Investigation. Al-Hazmy SM, Zouaghi MO, Al-Johani JN, Arfaoui Y, Al-Ashwal R, Hammami B, Alhagri IA, Alhemiary NA, Hamdi N. Molecules 27 5921 (2022)
  29. Methanolic Bark Extract of Abroma augusta (L.) Induces Apoptosis in EAC Cells through Altered Expression of Apoptosis Regulatory Genes. Miah M, Shimu AS, Mahmud S, Omar FB, Khatun R, Mohanto SC, Hoque KMF, Reza MA. Evid Based Complement Alternat Med 2020 9145626 (2020)
  30. Novel Synthesized N-Ethyl-Piperazinyl-Amides of C2-Substituted Oleanonic and Ursonic Acids Exhibit Cytotoxic Effects through Apoptotic Cell Death Regulation. Kazakova O, Mioc A, Smirnova I, Baikova I, Voicu A, Vlaia L, Macașoi I, Mioc M, Drăghici G, Avram Ş, Dehelean C, Şoica C. Int J Mol Sci 22 10967 (2021)
  31. Promising anti-leukemic effect of Zataria multiflora extract in combination with doxorubicin to combat acute lymphoblastic leukemia cells (Nalm-6) (in vitro and in silico). Lashkari M, Fatemi A, Valandani HM, Khalilabadi RM. Sci Rep 12 12657 (2022)
  32. Synthesis and Anticancer Activity of 1,3,4-Thiadiazoles with 3-Methoxyphenyl Substituent. Janowska S, Khylyuk D, Gornowicz A, Bielawska A, Janowski M, Czarnomysy R, Bielawski K, Wujec M. Molecules 27 6977 (2022)
  33. Weipiling decoction alleviates N-methyl-N-nitro-N'-nitrosoguanidine-induced gastric precancerous lesions via NF-κB signalling pathway inhibition. Yang P, Yang H, Zhou H, Li Q, Wei S, Wang Q, Yan Y, Liu Y, Pan H, Li S. Chin Med 17 104 (2022)
  34. An Intriguing Correlation Based on the Superimposition of Residue Pairs with Inhibitors that Target Protein-Protein Interfaces. Nakadai M, Tomida S, Sekimizu K. Sci Rep 6 18543 (2016)
  35. Development of method for three-point data estimation and SVR-QSAR model to screen anti cancer leads. Prakash O, Khan F. Comb Chem High Throughput Screen 16 425-434 (2013)
  36. Marine-Derived Streptomyces sennicomposti GMY01 with Anti-Plasmodial and Anticancer Activities: Genome Analysis, In Vitro Bioassay, Metabolite Profiling, and Molecular Docking. Widada J, Damayanti E, Mustofa M, Dinoto A, Febriansah R, Hertiani T. Microorganisms 11 1930 (2023)
  37. Novel Tetrahydro-[1,2,4]triazolo[3,4-a]isoquinoline Chalcones Suppress Breast Carcinoma through Cell Cycle Arrests and Apoptosis. Darwish MIM, Moustafa AM, Youssef AM, Mansour M, Yousef AI, El Omri A, Shawki HH, Mohamed MF, Hassaneen HM, Abdelhamid IA, Oishi H. Molecules 28 3338 (2023)
  38. Theoretical and molecular mechanistic investigations of novel (3-(furan-2-yl)pyrazol-4-yl) chalcones against lung carcinoma cell line (A549). Mohamed MF, Ibrahim NS, Saddiq AA, Almaghrabi OA, Al-Hazemi ME, Hassaneen HM, Abdelhamid IA. Naunyn Schmiedebergs Arch Pharmacol 396 719-736 (2023)
  39. Cytotoxic Activity of Amaryllidaceae Plants against Cancer Cells: Biotechnological, In Vitro, and In Silico Approaches. Trujillo L, Bedoya J, Cortés N, Osorio EH, Gallego JC, Leiva H, Castro D, Osorio E. Molecules 28 2601 (2023)
  40. Discovery of New 2-Phenylamino-3-acyl-1,4-naphthoquinones as Inhibitors of Cancer Cells Proliferation: Searching for Intra-Cellular Targets Playing a Role in Cancer Cells Survival. Benites J, Valderrama JA, Contreras Á, Enríquez C, Pino-Rios R, Yáñez O, Buc Calderon P. Molecules 28 4323 (2023)
  41. G. lucidum triterpenes restores intestinal flora balance in non-hepatitis B virus-related hepatocellular carcinoma: evidence of 16S rRNA sequencing and network pharmacology analysis. Xiong W, Yang C, Xia J, Wang W, Li N. Front Pharmacol 14 1197418 (2023)
  42. Molecular docking analysis of Bcl-2 with phyto-compounds. Kirubhanand C, Selvaraj J, Rekha UV, Vishnupriya V, Sivabalan V, Manikannan M, Nalini D, Vijayalakshmi P, Rajalakshmi M, Ponnulakshmi R. Bioinformation 16 468-473 (2020)
  43. Network pharmacology and molecular docking analysis on the mechanism of Tripterygium wilfordii Hook in the treatment of Sjögren syndrome. Wang Z, Xu Y, Liang S, Liang S. Medicine (Baltimore) 103 e37532 (2024)


Reviews citing this publication (6)

  1. From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors. Ashkenazi A, Fairbrother WJ, Leverson JD, Souers AJ. Nat Rev Drug Discov 16 273-284 (2017)
  2. HSP70 Multi-Functionality in Cancer. Albakova Z, Armeev GA, Kanevskiy LM, Kovalenko EI, Sapozhnikov AM. Cells 9 E587 (2020)
  3. Atropisomerism in medicinal chemistry: challenges and opportunities. Toenjes ST, Gustafson JL. Future Med Chem 10 409-422 (2018)
  4. Progress in targeting the BCL-2 family of proteins. Garner TP, Lopez A, Reyna DE, Spitz AZ, Gavathiotis E. Curr Opin Chem Biol 39 133-142 (2017)
  5. Cross Talk Between Cellular Redox State and the Antiapoptotic Protein Bcl-2. Pohl SÖ, Agostino M, Dharmarajan A, Pervaiz S. Antioxid Redox Signal 29 1215-1236 (2018)
  6. Adaptability in protein structures: structural dynamics and implications in ligand design. Maity A, Majumdar S, Priya P, De P, Saha S, Ghosh Dastidar S. J Biomol Struct Dyn 33 298-321 (2015)

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  1. Structures of BCL-2 in complex with venetoclax reveal the molecular basis of resistance mutations. Birkinshaw RW, Gong JN, Luo CS, Lio D, White CA, Anderson MA, Blombery P, Lessene G, Majewski IJ, Thijssen R, Roberts AW, Huang DCS, Colman PM, Czabotar PE. Nat Commun 10 2385 (2019)
  2. Evaluation and critical assessment of putative MCL-1 inhibitors. Varadarajan S, Vogler M, Butterworth M, Dinsdale D, Walensky LD, Cohen GM. Cell Death Differ 20 1475-1484 (2013)
  3. Cell death and the mitochondria: therapeutic targeting of the BCL-2 family-driven pathway. Roy MJ, Vom A, Czabotar PE, Lessene G. Br J Pharmacol 171 1973-1987 (2014)
  4. S55746 is a novel orally active BCL-2 selective and potent inhibitor that impairs hematological tumor growth. Casara P, Davidson J, Claperon A, Le Toumelin-Braizat G, Vogler M, Bruno A, Chanrion M, Lysiak-Auvity G, Le Diguarher T, Starck JB, Chen I, Whitehead N, Graham C, Matassova N, Dokurno P, Pedder C, Wang Y, Qiu S, Girard AM, Schneider E, Gravé F, Studeny A, Guasconi G, Rocchetti F, Maïga S, Henlin JM, Colland F, Kraus-Berthier L, Le Gouill S, Dyer MJS, Hubbard R, Wood M, Amiot M, Cohen GM, Hickman JA, Morris E, Murray J, Geneste O. Oncotarget 9 20075-20088 (2018)
  5. Molecular docking studies of anti-apoptotic BCL-2, BCL-XL, and MCL-1 proteins with ginsenosides from Panax ginseng. Sathishkumar N, Sathiyamoorthy S, Ramya M, Yang DU, Lee HN, Yang DC. J Enzyme Inhib Med Chem 27 685-692 (2012)
  6. Novel [(N-alkyl-3-indolylmethylene)hydrazono]oxindoles arrest cell cycle and induce cell apoptosis by inhibiting CDK2 and Bcl-2: synthesis, biological evaluation and in silico studies. Al-Warhi T, Abo-Ashour MF, Almahli H, Alotaibi OJ, Al-Sanea MM, Al-Ansary GH, Ahmed HY, Elaasser MM, Eldehna WM, Abdel-Aziz HA. J Enzyme Inhib Med Chem 35 1300-1309 (2020)
  7. Structural insights into the dual-targeting mechanism of Nutlin-3. Shin JS, Ha JH, He F, Muto Y, Ryu KS, Yoon HS, Kang S, Park SG, Park BC, Choi SU, Chi SW. Biochem Biophys Res Commun 420 48-53 (2012)
  8. Identification of a phenylacylsulfonamide series of dual Bcl-2/Bcl-xL antagonists. Perez HL, Banfi P, Bertrand J, Cai ZW, Grebinski JW, Kim K, Lippy J, Modugno M, Naglich J, Schmidt RJ, Tebben A, Vianello P, Wei DD, Zhang L, Galvani A, Lombardo LJ, Borzilleri RM. Bioorg Med Chem Lett 22 3946-3950 (2012)
  9. Selectivity by small-molecule inhibitors of protein interactions can be driven by protein surface fluctuations. Johnson DK, Karanicolas J. PLoS Comput Biol 11 e1004081 (2015)
  10. Atropisomeric small molecule Bcl-2 ligands: determination of bioactive conformation. Porter J, Payne A, Whitcombe I, de Candole B, Ford D, Garlish R, Hold A, Hutchinson B, Trevitt G, Turner J, Edwards C, Watkins C, Davis J, Stubberfield C. Bioorg Med Chem Lett 19 1767-1772 (2009)
  11. Application of the Exactive Plus EMR for automated protein-ligand screening by non-covalent mass spectrometry. Maple HJ, Scheibner O, Baumert M, Allen M, Taylor RJ, Garlish RA, Bromirski M, Burnley RJ. Rapid Commun Mass Spectrom 28 1561-1568 (2014)
  12. Towards the next generation of dual Bcl-2/Bcl-xL inhibitors. Varnes JG, Gero T, Huang S, Diebold RB, Ogoe C, Grover PT, Su M, Mukherjee P, Saeh JC, MacIntyre T, Repik G, Dillman K, Byth K, Russell DJ, Ioannidis S. Bioorg Med Chem Lett 24 3026-3033 (2014)
  13. Assessment of the Anticancer Effect of Chlorojanerin Isolated from Centaurothamnus maximus on A549 Lung Cancer Cells. Noman O, Nasr FA, Ahmed MZ, Rehman MT, Qamar W, Alqahtani AS, Guenther S. Molecules 28 3061 (2023)
  14. The Antiproliferative and Apoptotic Effects of a Novel Quinazoline Carrying Substituted-Sulfonamides: In Vitro and Molecular Docking Study. Alqahtani AS, Ghorab MM, Nasr FA, Ahmed MZ, Al-Mishari AA, Attia SM. Molecules 27 981 (2022)


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