Standard

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.

In: Journal of Enzyme Inhibition and Medicinal Chemistry, Vol. 35, No. 1, 01.01.2020, p. 245-254.

Research output: Contribution to journal › Article › peer-review

Harvard

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, vol. 35, no. 1, pp. 245-254. https://doi.org/10.1080/14756366.2019.1695795

APA

Pustenko, A., Nocentini, A., Balašova, A., Alafeefy, A., Krasavin, M., Žalubovskis, R., & Supuran, C. T. (2020). Aryl derivatives of 3H-1,2-benzoxathiepine 2,2-dioxide as carbonic anhydrase inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry, 35(1), 245-254. https://doi.org/10.1080/14756366.2019.1695795

Vancouver

Pustenko A, Nocentini A, Balašova A, Alafeefy A, Krasavin M, Žalubovskis R et al. Aryl derivatives of 3H-1,2-benzoxathiepine 2,2-dioxide as carbonic anhydrase inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry. 2020 Jan 1;35(1):245-254. https://doi.org/10.1080/14756366.2019.1695795

Author

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. In: Journal of Enzyme Inhibition and Medicinal Chemistry. 2020 ; Vol. 35, No. 1. pp. 245-254.

BibTeX

@article{37ca11983e3b4d1e968c634cfcc88a86,
title = "Aryl derivatives of 3H-1,2-benzoxathiepine 2,2-dioxide as carbonic anhydrase inhibitors",
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.",
keywords = "Carbonic anhydrase, homosulfocoumarin, isoform-selective inhibitor, sulfocoumarin, transmembrane isoforms, Humans, Structure-Activity Relationship, Dose-Response Relationship, Drug, Carbonic Anhydrase Inhibitors/chemical synthesis, Carbonic Anhydrases/metabolism, Molecular Structure, Isoenzymes/antagonists & inhibitors, Benzothiepins/chemical synthesis, POTENT",
author = "Aleksandrs Pustenko and Alessio Nocentini and Anastasija Bala{\v s}ova and Ahmed Alafeefy and Mikhail Krasavin and Raivis {\v Z}alubovskis and Supuran, {Claudiu T.}",
year = "2020",
month = jan,
day = "1",
doi = "10.1080/14756366.2019.1695795",
language = "English",
volume = "35",
pages = "245--254",
journal = "Journal of Enzyme Inhibition and Medicinal Chemistry",
issn = "1475-6366",
publisher = "Taylor & Francis",
number = "1",

}

RIS

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

KW - Humans

KW - Structure-Activity Relationship

KW - Dose-Response Relationship, Drug

KW - Carbonic Anhydrase Inhibitors/chemical synthesis

KW - Carbonic Anhydrases/metabolism

KW - Molecular Structure

KW - Isoenzymes/antagonists & inhibitors

KW - Benzothiepins/chemical synthesis

KW - POTENT

UR - http://www.scopus.com/inward/record.url?scp=85076014324&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/ffbe717e-d9c4-3f54-8e9f-9934d78f048f/

U2 - 10.1080/14756366.2019.1695795

DO - 10.1080/14756366.2019.1695795

M3 - Article

C2 - 31790605

AN - SCOPUS:85076014324

VL - 35

SP - 245

EP - 254

JO - Journal of Enzyme Inhibition and Medicinal Chemistry

JF - Journal of Enzyme Inhibition and Medicinal Chemistry

SN - 1475-6366

IS - 1

ER -

ID: 49810370