6b59 › Citations

Discovery of New Sulfonamide Carbonic Anhydrase IX Inhibitors Incorporating Nitrogenous Bases.

Nocentini A, Bua S, Lomelino CL, McKenna R, Menicatti M, Bartolucci G, Tenci B, Di Cesare Mannelli L, Ghelardini C, Gratteri P, Supuran CT
ACS Med Chem Lett 8 1314-1319 (2017)
Cited: 17 times
EuropePMC logo PMID: 29259754

Abstract

Incorporation of the purine/pyrimidine moieties as tails to classical benzenesulfonamide scaffolds afforded two series of human (h) carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. The compounds were designed according to the molecular hybridization approach, in order to modulate the interaction with different CA isozymes and exploit the antitumor effect of uracil and adenine derivatives in parallel and synergic mode to the inhibition of the tumor-associated hCA IX. The sulfonamides were investigated as inhibitors of four isoforms, cytosolic hCA I/II and transmembrane hCA IV/IX. The inhibitory profiles were dependent on the length and positioning of the spacer connecting the two pharmacophores. X-ray crystallography demonstrated the binding mode of an inhibitor to hCA II and hCA IX-mimic. Compounds endowed with the best hCA IX inhibitory efficacy were evaluated for antiproliferative activity against HT-29 colon cancer cell lines. The in vitro results suggest multiple mechanisms of action are responsible for the compounds' cytotoxic efficacy.

Reviews citing this publication (2)

  1. Carbonic anhydrase inhibitors as antitumor/antimetastatic agents: a patent review (2008-2018). Nocentini A, Supuran CT. Expert Opin Ther Pat 28 729-740 (2018)
  2. Targeting carbonic anhydrase IX and XII isoforms with small molecule inhibitors and monoclonal antibodies. Kciuk M, Gielecińska A, Mujwar S, Mojzych M, Marciniak B, Drozda R, Kontek R. J Enzyme Inhib Med Chem 37 1278-1298 (2022)

Articles citing this publication (15)

  1. Steroids interfere with human carbonic anhydrase activity by using alternative binding mechanisms. Nocentini A, Bonardi A, Gratteri P, Cerra B, Gioiello A, Supuran CT. J Enzyme Inhib Med Chem 33 1453-1459 (2018)
  2. Discovery of novel 1,3-diaryltriazene sulfonamides as carbonic anhydrase I, II, VII, and IX inhibitors. Akocak S, Lolak N, Bua S, Supuran CT. J Enzyme Inhib Med Chem 33 1575-1580 (2018)
  3. Drug Screening in Human Cells by NMR Spectroscopy Allows the Early Assessment of Drug Potency. Luchinat E, Barbieri L, Cremonini M, Nocentini A, Supuran CT, Banci L. Angew Chem Int Ed Engl 59 6535-6539 (2020)
  4. Inhibition studies on a panel of human carbonic anhydrases with N1-substituted secondary sulfonamides incorporating thiazolinone or imidazolone-indole tails. Awadallah FM, Bua S, Mahmoud WR, Nada HH, Nocentini A, Supuran CT. J Enzyme Inhib Med Chem 33 629-638 (2018)
  5. Natural Polyphenols Selectively Inhibit β-Carbonic Anhydrase from the Dandruff-Producing Fungus Malassezia globosa: Activity and Modeling Studies. Nocentini A, Bua S, Del Prete S, Heravi YE, Saboury AA, Karioti A, Bilia AR, Capasso C, Gratteri P, Supuran CT. ChemMedChem 13 816-823 (2018)
  6. Carbonic anhydrase inhibition with a series of novel benzenesulfonamide-triazole conjugates. El-Gazzar MG, Nafie NH, Nocentini A, Ghorab MM, Heiba HI, Supuran CT. J Enzyme Inhib Med Chem 33 1565-1574 (2018)
  7. Phaeodactylum tricornutum as a model organism for testing the membrane penetrability of sulphonamide carbonic anhydrase inhibitors. Rogato A, Del Prete S, Nocentini A, Carginale V, Supuran CT, Capasso C. J Enzyme Inhib Med Chem 34 510-518 (2019)
  8. Inhibitory activity against carbonic anhydrase IX and XII as a candidate selection criterion in the development of new anticancer agents. Krasavin M, Kalinin S, Sharonova T, Supuran CT. J Enzyme Inhib Med Chem 35 1555-1561 (2020)
  9. Aromatic Sulfonamides including a Sulfonic Acid Tail: New Membrane Impermeant Carbonic Anhydrase Inhibitors for Targeting Selectively the Cancer-Associated Isoforms. Giovannuzzi S, D'Ambrosio M, Luceri C, Osman SM, Pallecchi M, Bartolucci G, Nocentini A, Supuran CT. Int J Mol Sci 23 461 (2021)
  10. Isocoumarins: a new class of selective carbonic anhydrase IX and XII inhibitors. Onyılmaz M, Koca M, Bonardi A, Degirmenci M, Supuran CT. J Enzyme Inhib Med Chem 37 743-748 (2022)
  11. Design and synthesis of some new benzoylthioureido phenyl derivatives targeting carbonic anhydrase enzymes. Najm MAA, Mahmoud WR, Taher AT, Abbas SE, Awadallah FM, Allam HA, Vullo D, Supuran CT. J Enzyme Inhib Med Chem 37 2702-2709 (2022)
  12. Synthesis and cytotoxic activities of novel copper and silver complexes of 1,3-diaryltriazene-substituted sulfonamides. Canakci D, Koyuncu I, Lolak N, Durgun M, Akocak S, Supuran CT. J Enzyme Inhib Med Chem 34 110-116 (2019)
  13. Bis-pharmacophore of cinnamaldehyde-clubbed thiosemicarbazones as potent carbonic anhydrase-II inhibitors. Rasool A, Batool Z, Khan M, Halim SA, Shafiq Z, Temirak A, Salem MA, Ali TE, Khan A, Al-Harrasi A. Sci Rep 12 16095 (2022)
  14. Pyrazole-sulfonamide scaffold featuring dual-tail strategy as apoptosis inducers in colon cancer. El-Hazek RMM, Zaher NH, Emam HES, El-Gazzar MG, Khalil A. Sci Rep 13 5782 (2023)
  15. The Mechanism of Anti-Tumor Activity of 6-Morpholino- and 6-Amino-9-Sulfonylpurine Derivatives on Human Leukemia Cells. Leventić M, Opačak-Bernardi T, Rastija V, Matić J, Pavlović Saftić D, Ban Ž, Žinić B, Glavaš-Obrovac L. Molecules 28 6136 (2023)


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