Aryl derivatives of 3H-1,2-benzoxathiepine 2,2-dioxide as carbonic anhydrase inhibitors

Aleksandrs Pustenko, Alessio Nocentini, Anastasija Balašova, Ahmed Alafeefy, Mikhail Krasavin, Raivis Žalubovskis, Claudiu T. Supuran

Результат исследований: Научные публикации в периодических изданияхстатья

Выдержка

A new series of homosulfocoumarins (3H-1,2-benzoxathiepine 2,2-dioxides) possessing various substitution patterns and moieties in the 7, 8 or 9 position of the heterocylic ring were prepared by original procedures and investigated for the inhibition of four physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the human (h) hCA I, II, IX and XII. The 8-substituted homosulfocoumarins were the most effective hCA IX/XII inhibitors followed by the 7-substituted derivatives, whereas the substitution pattern in position 9 led to less effective binders for the transmembrane, tumour-associated isoforms IX/XII. The cytosolic isoforms hCA I and II were not inhibited by these compounds, similar to the sulfocoumarins/coumarins investigated earlier. As hCA IX and XII are validated anti-tumour targets, with one sulphonamide (SLC-0111) in Phase Ib/II clinical trials, finding derivatives with better selectivity for inhibiting the tumour-associated isoforms over the cytosolic ones, as the homosulfocoumarins reported here, is of crucial importance.

Язык оригиналаанглийский
Страницы (с-по)245-254
ЖурналJournal of Enzyme Inhibition and Medicinal Chemistry
Том35
Номер выпуска1
Ранняя дата в режиме онлайн2 дек 2019
DOI
СостояниеОпубликовано - 1 янв 2020

Отпечаток

Carbonic Anhydrase Inhibitors
Protein Isoforms
Coumarins
Neoplasms
Phase II Clinical Trials
Carbonic Anhydrases
Sulfonamides

Предметные области Scopus

  • Фармакология
  • Поиск новых лекарств

Цитировать

Pustenko, Aleksandrs ; Nocentini, Alessio ; Balašova, Anastasija ; Alafeefy, Ahmed ; Krasavin, Mikhail ; Žalubovskis, Raivis ; Supuran, Claudiu T. / Aryl derivatives of 3H-1,2-benzoxathiepine 2,2-dioxide as carbonic anhydrase inhibitors. В: Journal of Enzyme Inhibition and Medicinal Chemistry. 2020 ; Том 35, № 1. стр. 245-254.
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abstract = "A new series of homosulfocoumarins (3H-1,2-benzoxathiepine 2,2-dioxides) possessing various substitution patterns and moieties in the 7, 8 or 9 position of the heterocylic ring were prepared by original procedures and investigated for the inhibition of four physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the human (h) hCA I, II, IX and XII. The 8-substituted homosulfocoumarins were the most effective hCA IX/XII inhibitors followed by the 7-substituted derivatives, whereas the substitution pattern in position 9 led to less effective binders for the transmembrane, tumour-associated isoforms IX/XII. The cytosolic isoforms hCA I and II were not inhibited by these compounds, similar to the sulfocoumarins/coumarins investigated earlier. As hCA IX and XII are validated anti-tumour targets, with one sulphonamide (SLC-0111) in Phase Ib/II clinical trials, finding derivatives with better selectivity for inhibiting the tumour-associated isoforms over the cytosolic ones, as the homosulfocoumarins reported here, is of crucial importance.",
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author = "Aleksandrs Pustenko and Alessio Nocentini and Anastasija Balašova and Ahmed Alafeefy and Mikhail Krasavin and Raivis Žalubovskis and Supuran, {Claudiu T.}",
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Pustenko, A, Nocentini, A, Balašova, A, Alafeefy, A, Krasavin, M, Žalubovskis, R & Supuran, CT 2020, 'Aryl derivatives of 3H-1,2-benzoxathiepine 2,2-dioxide as carbonic anhydrase inhibitors', Journal of Enzyme Inhibition and Medicinal Chemistry, том. 35, № 1, стр. 245-254. https://doi.org/10.1080/14756366.2019.1695795

Aryl derivatives of 3H-1,2-benzoxathiepine 2,2-dioxide as carbonic anhydrase inhibitors. / Pustenko, Aleksandrs; Nocentini, Alessio; Balašova, Anastasija; Alafeefy, Ahmed; Krasavin, Mikhail; Žalubovskis, Raivis; Supuran, Claudiu T.

В: Journal of Enzyme Inhibition and Medicinal Chemistry, Том 35, № 1, 01.01.2020, стр. 245-254.

Результат исследований: Научные публикации в периодических изданияхстатья

TY - JOUR

T1 - Aryl derivatives of 3H-1,2-benzoxathiepine 2,2-dioxide as carbonic anhydrase inhibitors

AU - Pustenko, Aleksandrs

AU - Nocentini, Alessio

AU - Balašova, Anastasija

AU - Alafeefy, Ahmed

AU - Krasavin, Mikhail

AU - Žalubovskis, Raivis

AU - Supuran, Claudiu T.

PY - 2020/1/1

Y1 - 2020/1/1

N2 - A new series of homosulfocoumarins (3H-1,2-benzoxathiepine 2,2-dioxides) possessing various substitution patterns and moieties in the 7, 8 or 9 position of the heterocylic ring were prepared by original procedures and investigated for the inhibition of four physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the human (h) hCA I, II, IX and XII. The 8-substituted homosulfocoumarins were the most effective hCA IX/XII inhibitors followed by the 7-substituted derivatives, whereas the substitution pattern in position 9 led to less effective binders for the transmembrane, tumour-associated isoforms IX/XII. The cytosolic isoforms hCA I and II were not inhibited by these compounds, similar to the sulfocoumarins/coumarins investigated earlier. As hCA IX and XII are validated anti-tumour targets, with one sulphonamide (SLC-0111) in Phase Ib/II clinical trials, finding derivatives with better selectivity for inhibiting the tumour-associated isoforms over the cytosolic ones, as the homosulfocoumarins reported here, is of crucial importance.

AB - A new series of homosulfocoumarins (3H-1,2-benzoxathiepine 2,2-dioxides) possessing various substitution patterns and moieties in the 7, 8 or 9 position of the heterocylic ring were prepared by original procedures and investigated for the inhibition of four physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the human (h) hCA I, II, IX and XII. The 8-substituted homosulfocoumarins were the most effective hCA IX/XII inhibitors followed by the 7-substituted derivatives, whereas the substitution pattern in position 9 led to less effective binders for the transmembrane, tumour-associated isoforms IX/XII. The cytosolic isoforms hCA I and II were not inhibited by these compounds, similar to the sulfocoumarins/coumarins investigated earlier. As hCA IX and XII are validated anti-tumour targets, with one sulphonamide (SLC-0111) in Phase Ib/II clinical trials, finding derivatives with better selectivity for inhibiting the tumour-associated isoforms over the cytosolic ones, as the homosulfocoumarins reported here, is of crucial importance.

KW - Carbonic anhydrase

KW - homosulfocoumarin

KW - isoform-selective inhibitor

KW - sulfocoumarin

KW - transmembrane isoforms

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U2 - 10.1080/14756366.2019.1695795

DO - 10.1080/14756366.2019.1695795

M3 - Article

C2 - 31790605

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SP - 245

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JO - Journal of Enzyme Inhibition and Medicinal Chemistry

JF - Journal of Enzyme Inhibition and Medicinal Chemistry

SN - 1475-6366

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