Development of Novel Indole-3-sulfonamide-heteroaryl Hybrids as Carbonic Anhydrase Inhibitors: Design, Synthesis and in-vitro Screening

  • Авторлар: Chinchilli K.1, Singh P.2, Swain B.1, Goud N.3, Sigalapalli D.4, Choli A.1, Angeli A.5, Nanduri S.6, Yaddanapudi V.7, Supuran C.8, Arifuddin M.9
  • Мекемелер:
    1. Department of Medicinal Chemistry,, National Institute of Pharmaceutical Education and Research (NIPER)
    2. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER)
    3. Department of Neuroimaging and Interventional Radiology (NIIR), National Institute of Mental Health and Neuro Sciences (NIMHANS)
    4. Department of Pharmaceutical Chemistry, Vignan Pharmacy College, Jawaharlal Nehru Technological University
    5. Dipartimento Neurofarba, Sezione Di Scienze Farmaceutiche E Nutraceutiche e Laboratorio Di Chimica Bioinorganica, Universita` Degli Studi Di Firenze, Sesto Fiorentino,
    6. Department of Medicinal Chemistry,, National Institute of Pharmaceutical Education and Research (NIPER)
    7. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER)
    8. Dipartimento Neurofarba, Sezione Di Scienze Farmaceutiche E Nutraceutiche e Laboratorio Di Chimica Bioinorganica, , Universita` Degli Studi Di Firenze, Sesto Fiorentino,
    9. Department of Chemistry, Directorate of Distance Education,, Maulana Azad National Urdu University
  • Шығарылым: Том 23, № 11 (2023)
  • Беттер: 1225-1233
  • Бөлім: Oncology
  • URL: https://kld-journal.fedlab.ru/1871-5206/article/view/694293
  • DOI: https://doi.org/10.2174/1871520623666230227092821
  • ID: 694293

Дәйексөз келтіру

Толық мәтін

Аннотация

Background: Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the reversible hydration of carbon dioxide to bicarbonate and a proton. Inhibition of isoforms IX and XII has induced potent anticancer effects.

Objective: A series of indole-3-sulfonamide-heteroaryl hybrid (6a-y) was synthesized and screened for the inhibition of human (h) hCA isoforms I, II, IX, and XII.

Methods: The synthesis of target compounds (6a-y) was carried out in multistep starting from 5-nitro indole as starting material by using classical reported reaction conditions. The steps involved are N-Alkylation Chlorosulfonation, amination, reduction, and finally amidation reaction.

Results: Amongst all the compounds (6a-y) synthesized and screened, 6l was found to be active against all the screened hCA isoforms, with Ki ranging 8.03 µM, 4.15 µM, 7.09 µM, and 4.06 µM respectively. On the other hand, 6i, 6j, 6q, 6s, and 6t were highly selective against tumor-associated hCA IX, and 6u was selective against both hCA II and hCA IX with moderate inhibitory activities under the range of 100 µM. These compounds showed good activity against the tumor-associated hCA IX and might be developed as future drug leads for anticancer drug discovery.

Conclusion: These compounds may be useful as starting points for the design and development of more selective and potent hCA IX and XII inhibitors.

Авторлар туралы

Krishna Chinchilli

Department of Medicinal Chemistry,, National Institute of Pharmaceutical Education and Research (NIPER)

Email: info@benthamscience.net

Priti Singh

Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER)

Email: info@benthamscience.net

Baijayantimala Swain

Department of Medicinal Chemistry,, National Institute of Pharmaceutical Education and Research (NIPER)

Email: info@benthamscience.net

Nerella Goud

Department of Neuroimaging and Interventional Radiology (NIIR), National Institute of Mental Health and Neuro Sciences (NIMHANS)

Email: info@benthamscience.net

Dilep Sigalapalli

Department of Pharmaceutical Chemistry, Vignan Pharmacy College, Jawaharlal Nehru Technological University

Email: info@benthamscience.net

Abhishek Choli

Department of Medicinal Chemistry,, National Institute of Pharmaceutical Education and Research (NIPER)

Email: info@benthamscience.net

Andrea Angeli

Dipartimento Neurofarba, Sezione Di Scienze Farmaceutiche E Nutraceutiche e Laboratorio Di Chimica Bioinorganica, Universita` Degli Studi Di Firenze, Sesto Fiorentino,

Email: info@benthamscience.net

Srinivas Nanduri

Department of Medicinal Chemistry,, National Institute of Pharmaceutical Education and Research (NIPER)

Хат алмасуға жауапты Автор.
Email: info@benthamscience.net

Venkata Yaddanapudi

Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER)

Email: info@benthamscience.net

Claudiu Supuran

Dipartimento Neurofarba, Sezione Di Scienze Farmaceutiche E Nutraceutiche e Laboratorio Di Chimica Bioinorganica, , Universita` Degli Studi Di Firenze, Sesto Fiorentino,

Хат алмасуға жауапты Автор.
Email: info@benthamscience.net

Mohammed Arifuddin

Department of Chemistry, Directorate of Distance Education,, Maulana Azad National Urdu University

Хат алмасуға жауапты Автор.
Email: info@benthamscience.net

Әдебиет тізімі

  1. Supuran, C.T. Structure and function of carbonic anhydrases. Biochem. J., 2016, 473(14), 2023-2032. doi: 10.1042/BCJ20160115 PMID: 27407171
  2. Supuran, C.T. Emerging role of carbonic anhydrase inhibitors. Clin. Sci., 2021, 135(10), 1233-1249. doi: 10.1042/CS20210040 PMID: 34013961
  3. Thacker, P.S.; Shaikh, P.; Angeli, A.; Arifuddin, M.; Supuran, C.T. Synthesis and biological evaluation of novel 8-substituted quinoline-2-carboxamides as carbonic anhydrase inhibitors. J. Enzyme Inhib. Med. Chem., 2019, 34(1), 1172-1177. doi: 10.1080/14756366.2019.1626376 PMID: 31218888
  4. Swain, B. 3-functionalized benzenesulphonamide based 1,3,4-oxadiazoles as selective carbonic anhydrase XIII inhibitors: Design, syn-thesis and biological evaluation. Bioorg. Med. Chem. Lett., 2021, 37, 127856. doi: 10.1016/j.bmcl.2021.127856 PMID: 33609663
  5. Supuran, C. Carbonic anhydrases-an overview. Curr. Pharm. Des., 2008, 14(7), 603-614. doi: 10.2174/138161208783877884 PMID: 18336305
  6. Supuran, C.T. Carbonic anhydrases: Novel therapeutic applications for inhibitors and activators. Nat. Rev. Drug Discov., 2008, 7(2), 168-181. doi: 10.1038/nrd2467 PMID: 18167490
  7. Ozensoy Guler, O.; Capasso, C.; Supuran, C.T. A magnificent enzyme superfamily: Carbonic anhydrases, their purification and characteri-zation. J. Enzyme Inhib. Med. Chem., 2016, 31(5), 689-694. doi: 10.3109/14756366.2015.1059333 PMID: 26118417
  8. Grandane, A.; Nocentini, A.; Werner, T.; Zalubovskis, R.; Supuran, C.T. Benzoxepinones: A new isoform-selective class of tumor associ-ated carbonic anhydrase inhibitors. Bioorg. Med. Chem., 2020, 28(11), 115496. doi: 10.1016/j.bmc.2020.115496 PMID: 32327349
  9. Supuran, C.T.; Scozzafava, A. Carbonic anhydrase inhibitors and their therapeutic potential. Expert Opin. Ther. Pat., 2000, 10(5), 575-600. doi: 10.1517/13543776.10.5.575 PMID: 30217119
  10. Boone, C.; Habibzadegan, A.; Gill, S.; McKenna, R. Carbonic anhydrases and their biotechnological applications. Biomolecules, 2013, 3(4), 553-562. doi: 10.3390/biom3030553 PMID: 24970180
  11. Lomelino, C.; McKenna, R. Carbonic anhydrase inhibitors: A review on the progress of patent literature (2011-2016). Expert Opin. Ther. Pat., 2016, 26(8), 947-956. doi: 10.1080/13543776.2016.1203904 PMID: 27387065
  12. Supuran, C.T.; Scozzafava, A.; Casini, A. Carbonic anhydrase inhibitors. Med. Res. Rev., 2003, 23(2), 146-189. doi: 10.1002/med.10025 PMID: 12500287
  13. a) Sugrue, M.F. Prog. Retin. Eye Res., 2000, 19, 87-112.; b) Supuran, C.T. Therapeutic applications of carbonic anhydrase inhibitors. Therapy, 2007, 4, 355-378.
  14. Kim, J.K.; Lee, C.; Lim, S.W.; Adhikari, A.; Andring, J.T.; McKenna, R.; Ghim, C.M.; Kim, C.U. Elucidating the role of metal ions in car-bonic anhydrase catalysis. Nat. Commun., 2020, 11(1), 4557. doi: 10.1038/s41467-020-18425-5 PMID: 32917908
  15. Coleman, J.E. Mechanism of action of carbonic anhydrase. Subtrate, sulfonamide, and anion binding. J. Biol. Chem., 1967, 242(22), 5212-5219. doi: 10.1016/S0021-9258(18)99413-5 PMID: 4965135
  16. A review on biological importance of heterocyclic compounds. Pharma Chem., 2017, 9, 141-147.
  17. Asif, M. Biological potential and chemical properties of pyridine and piperidine fused pyridazine compounds: Pyridopyridazine a versatile nucleus. Asian J. Pharm., 2016, 1, 29-35.
  18. Asif, M.A. Mini review: Biological significance of nitrogen heteroatom containing heterocyclic compounds. Int. J. Bioorg. Chem., 2017, 2, 146-152.
  19. Arora, P.; Varun Arora, V.; Lamba, H.S.; Wadhwa, D. Impotance of heterocyclic chemistry a review. Int. J. Pharm. Sci. Res., 2012, 3, 2947-2954.
  20. Tahlan, S.; Kumar, S.; Narasimhan, B. Pharmacological significance of heterocyclic 1H-benzimidazole scaffolds: A review. BMC Chem., 2019, 13(1), 101. doi: 10.1186/s13065-019-0625-4 PMID: 31410412
  21. a) Singh, P.; Swain, B.; Thacker, P.S.; Sigalapalli, D.K.; Purnachander Yadav, P.; Angeli, A.; Supuran, C.T.; Arifuddin, M. Synthesis and carbonic anhydrase inhibition studies of sulfonamide based indole-1,2,3-triazole chalcone hybrids. Bioorg. Chem., 2020, 99, 103839. doi: 10.1016/j.bioorg.2020.103839 PMID: 32289586; b) Singh, P.; Choli, A.; Swain, B.; Angeli, A.; Sahoo, S.K.; Yaddanapudi, V.M.; Supuran, C.T.; Arifuddin, M. Design and development of novel series of indole‐3‐sulfonamide ureido derivatives as selective carbonic anhydrase II inhibitors. Arch. Pharm., 2022, 355(1), 2100333. doi: 10.1002/ardp.202100333 PMID: 34694638
  22. Husain, A.; Madhesia, D. Heterocyclic compounds as carbonic anhydrase inhibitor. J. Enzyme Inhib. Med. Chem., 2012, 27(6), 773-783. doi: 10.3109/14756366.2011.617882 PMID: 21981003
  23. a) Monti, S.M.; Meccariello, A.; Ceruso, M.; Szafrański, K.; Sławiński, J.; Supuran, C.T. Inhibition studies of Brucella suis β-carbonic anhydrases with a series of 4-substituted pyridine-3-sulphonamides. J. Enzyme Inhib. Med. Chem., 2018, 33(1), 255-259. doi: 10.1080/14756366.2017.1413097 PMID: 29271264; b) Sławiński, J.; Szafrański, K.; Vullo, D.; Supuran, C.T. Carbonic anhydrase inhibitors. Synthesis of heterocyclic 4-substituted pyridine-3-sulfonamide derivatives and their inhibition of the human cytosolic isozymes I and II and transmembrane tumor-associated isozymes IX and XII. Eur. J. Med. Chem., 2013, 69, 701-710. doi: 10.1016/j.ejmech.2013.09.027 PMID: 24095761
  24. Lehtonen, J.M.; Parkkila, S.; Vullo, D.; Casini, A.; Scozzafava, A.; Supuran, C.T. Carbonic anhydrase inhibitors. Inhibition of cytosolic isozyme XIII with aromatic and heterocyclic sulfonamides: A novel target for the drug design. Bioorg. Med. Chem. Lett., 2004, 14(14), 3757-3762. doi: 10.1016/j.bmcl.2004.04.106 PMID: 15203157
  25. a) Angapelly, S.; Sri Ramya, P.V.; Angeli, A.; Supuran, C.T.; Arifuddin, M. Sulfocoumarin, coumarin, 4-sulfamoylphenyl-bearing inda-zole-3-carboxamide hybrids: Synthesis and selective inhibition of tumor-associated carbonic anhydrase isozymes IX and XII. ChemMedChem, 2017, 12(19), 1578-1584. doi: 10.1002/cmdc.201700446 PMID: 28940980; b) Angapelly, S.; Angeli, A.; Khan, A.J.; Sri Ramya, P.V.; Supuran, C.T.; Arifuddin, M. Synthesis and Biological evaluation of 4-Sulfamoylphenyl/sulfocoumarin carboxamides as selective inhibitors of carbonic anhydrase isoforms hCA II, IX,and XII. ChemMedChem, 2018, 13(12), 1165-1171. doi: 10.1002/cmdc.201800180 PMID: 29675887; c) Angapelly, S.; Ramya, P.V.S.; Sodhi, R.; Angeli, A.; Rangan, K.; Nagesh, N.; Supuran, C.T.; Arifuddin, M. Iodine-mediated one-pot in-tramolecular decarboxylation domino reaction for accessing functionalised 2-(1,3,4-oxadiazol-2-yl)anilines with carbonic anhydrase in-hibitory action. J. Enzyme Inhib. Med. Chem., 2018, 33(1), 615-628. doi: 10.1080/14756366.2018.1443447 PMID: 29536768
  26. Singh, P.; Purnachander Yadav, P.; Swain, B.; Thacker, P.S.; Angeli, A.; Supuran, C.T.; Arifuddin, M. Discovery of a novel series of in-dolylchalcone-benzenesulfonamide hybrids acting as selective carbonic anhydrase II inhibitors. Bioorg. Chem., 2021, 108, 104647. doi: 10.1016/j.bioorg.2021.104647 PMID: 33530019
  27. Rogers, J.I.; Mukherjee, J.; Khalifah, R.G. Interaction of amide inhibitors with the active site of carbonic anhydrase: Metal-induced depro-tonation of the bound amide group is indicated by slow binding kinetics, by visible spectra of complexes with cobalt enzyme, and by pH effects on binding affinity. Biochemistry, 1987, 26(18), 5672-5679. doi: 10.1021/bi00392a014 PMID: 3118948
  28. Chiaramonte, N.; Romanelli, M.; Teodori, E.; Supuran, C. Amino acids as building blocks for carbonic anhydrase inhibitors. Metabolites, 2018, 8(2), 36. doi: 10.3390/metabo8020036 PMID: 29795039
  29. Ostacolo, C.; Di Sarno, V.; Lauro, G.; Pepe, G.; Musella, S.; Ciaglia, T.; Vestuto, V.; Autore, G.; Bifulco, G.; Marzocco, S.; Campiglia, P.; Gomez-Monterrey, I.M.; Bertamino, A. Identification of an indol-based multi-target kinase inhibitor through phenotype screening and tar-get fishing using inverse virtual screening approach. Eur. J. Med. Chem., 2019, 167, 61-75. doi: 10.1016/j.ejmech.2019.01.066 PMID: 30763817
  30. Swain, B.; Angeli, A.; Angapelly, S.; Thacker, P.S.; Singh, P.; Supuran, C.T.; Arifuddin, M. Synthesis of a new series of 3-functionalised-1-phenyl-1,2,3-triazole sulfamoylbenzamides as carbonic anhydrase I, II, IV and IX inhibitors. J. Enzyme Inhib. Med. Chem., 2019, 34(1), 1199-1209. doi: 10.1080/14756366.2019.1629432 PMID: 31237458
  31. Thacker, P.S.; Srikanth, D.; Angeli, A.; Singh, P.; Chinchilli, K.K.; Arifuddin, M.; Supuran, C.T. Coumarin-thiourea hybrids show potent carbonic anhydrase IX and XIII inhibitory action. ChemMedChem, 2021, 16(8), 1252-1256. doi: 10.1002/cmdc.202000915 PMID: 33346945
  32. Swain, B.; Singh Digwal, C.; Angeli, A.; Alvala, M.; Singh, P.; Supuran, C.T.; Arifuddin, M. Synthesis and exploration of 2-morpholino-4-phenylthiazol-5-yl acrylamide derivatives for their effects against carbonic anhydrase I, II, IX and XII isoforms as a non-sulfonamide class of inhibitors. Bioorg. Med. Chem., 2019, 27(21), 115090. doi: 10.1016/j.bmc.2019.115090 PMID: 31515058
  33. Khalifah, R.G. The carbon dioxide hydration activity of carbonic anhydrase. I. Stop-flow kinetic studies on the native human isoenzymes B and C. J. Biol. Chem., 1971, 246(8), 2561-2573. doi: 10.1016/S0021-9258(18)62326-9 PMID: 4994926
  34. a) Korkmaz, N.; Obaidi, O.A.; Senturk, M.; Astley, D.; Ekinci, D.; Supuran, C.T. Synthesis and biological activity of novel thiourea de-rivatives as carbonic anhydrase inhibitors. J. Enzyme Inhib. Med. Chem., 2015, 30(1), 75-80. doi: 10.3109/14756366.2013.879656 PMID: 24666304; b) Akdemir, A.; De Monte, C.; Carradori, S.; Supuran, C.T. Computational investigation of the selectivity of salen and tetrahydrosalen compounds towards the tumor-associated hCA XII isozyme. J. Enzyme Inhib. Med. Chem., 2015, 30(1), 114-118. doi: 10.3109/14756366.2014.892936 PMID: 24666302; c) Nishimori, I.; Vullo, D.; Innocenti, A.; Scozzafava, A.; Mastrolorenzo, A.; Supuran, C.T. Carbonic anhydrase inhibitors. The mito-chondrial isozyme VB as a new target for sulfonamide and sulfamate inhibitors. J. Med. Chem., 2005, 48(24), 7860-7866. doi: 10.1021/jm050483n PMID: 16302824
  35. a) Göçer, H.; Akincioğlu, A.; Göksu, S.; Gülçin, İ.; Supuran, C.T. Carbonic anhydrase and acetylcholinesterase inhibitory effects of car-bamates and sulfamoylcarbamates. J. Enzyme Inhib. Med. Chem., 2015, 30(2), 316-320. doi: 10.3109/14756366.2014.928704 PMID: 24964347; b) Ceruso, M.; Bragagni, M.; AlOthman, Z.; Osman, S.M.; Supuran, C.T. New series of sulfonamides containing amino acid moiety act as effective and selective inhibitors of tumor-associated carbonic anhydrase XII. J. Enzyme Inhib. Med. Chem., 2015, 30(3), 430-434. doi: 10.3109/14756366.2014.942659 PMID: 25089707
  36. a) Supuran, C.T.; Barboiu, M.; Luca, C.; Pop, E.; Brewster, M.E.; Dinculescu, A. Synthesis of mono and bis pyridinium salt derivatives of 2-amino-5-(2-aminoethyl)-and 2-amino-5-(3-aminopropyl)-1,3,4-thiadiazole and their interaction with isozyme II. Eur. J. Med. Chem., 1996, 31, 597-606. doi: 10.1016/0223-5234(96)89555-9; b) Puccetti, L.; Fasolis, G.; Vullo, D.; Chohan, Z.H.; Scozzafava, A.; Supuran, C.T. Carbonic anhydrase inhibitors. Inhibition of cyto-solic/tumor-associated carbonic anhydrase isozymes I, II, IX, and XII with Schiff's bases incorporating chromone and aromatic sulfona-mide moieties, and their zinc complexes. Bioorg. Med. Chem. Lett., 2005, 15(12), 3096-3101. doi: 10.1016/j.bmcl.2005.04.055 PMID: 15908204

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