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From random to rational: A discovery approach to selective subnanomolar inhibitors of human carbonic anhydrase IV based on the Castagnoli-Cushman multicomponent reaction. / Kalinin, Stanislav; Nocentini, Alessio; Kovalenko, Alexander; Sharoyko, Vladimir; Bonardi, Alessandro; Angeli, Andrea; Gratteri, Paola; Tennikova, Tatiana B.; Supuran, Claudiu T.; Krasavin, Mikhail.

In: European Journal of Medicinal Chemistry, Vol. 182, 111642, 15.11.2019.

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

Harvard

Kalinin, S, Nocentini, A, Kovalenko, A, Sharoyko, V, Bonardi, A, Angeli, A, Gratteri, P, Tennikova, TB, Supuran, CT & Krasavin, M 2019, 'From random to rational: A discovery approach to selective subnanomolar inhibitors of human carbonic anhydrase IV based on the Castagnoli-Cushman multicomponent reaction', European Journal of Medicinal Chemistry, vol. 182, 111642. https://doi.org/10.1016/j.ejmech.2019.111642

APA

Kalinin, S., Nocentini, A., Kovalenko, A., Sharoyko, V., Bonardi, A., Angeli, A., Gratteri, P., Tennikova, T. B., Supuran, C. T., & Krasavin, M. (2019). From random to rational: A discovery approach to selective subnanomolar inhibitors of human carbonic anhydrase IV based on the Castagnoli-Cushman multicomponent reaction. European Journal of Medicinal Chemistry, 182, [111642]. https://doi.org/10.1016/j.ejmech.2019.111642

Vancouver

Kalinin S, Nocentini A, Kovalenko A, Sharoyko V, Bonardi A, Angeli A et al. From random to rational: A discovery approach to selective subnanomolar inhibitors of human carbonic anhydrase IV based on the Castagnoli-Cushman multicomponent reaction. European Journal of Medicinal Chemistry. 2019 Nov 15;182. 111642. https://doi.org/10.1016/j.ejmech.2019.111642

Author

Kalinin, Stanislav ; Nocentini, Alessio ; Kovalenko, Alexander ; Sharoyko, Vladimir ; Bonardi, Alessandro ; Angeli, Andrea ; Gratteri, Paola ; Tennikova, Tatiana B. ; Supuran, Claudiu T. ; Krasavin, Mikhail. / From random to rational: A discovery approach to selective subnanomolar inhibitors of human carbonic anhydrase IV based on the Castagnoli-Cushman multicomponent reaction. In: European Journal of Medicinal Chemistry. 2019 ; Vol. 182.

BibTeX

@article{a40a8815e1da47df88725b76fefe31b8,
title = "From random to rational: A discovery approach to selective subnanomolar inhibitors of human carbonic anhydrase IV based on the Castagnoli-Cushman multicomponent reaction",
abstract = "By exploiting the power of multicomponent chemistry, a relatively small, diverse set of primary sulfonamides was synthesized and screened against a panel of human carbonic anhydrases to reveal a low-nanomolar, albeit non-selective hCA IV lead inhibitor. Investigation of the docking poses of this compound identified a hydrophilic pocket unique to hCA IV and conveniently positioned near the carboxylate functionality of the initial lead. Various residues capable of forming hydrogen bonds as well as salt bridges were placed in this pocket via a carboxamides linkage, which led to drastic improvement of potency and selectivity towards hCA IV. This improvement of the desired inhibitory profile was rationalized by the new contacts as had been envisioned. These new tool compounds were shown to possess selective, dose-dependent cytotoxicity against human glioma T98G cell line. The latter showed a substantially increased hCA IV mRNA expression under hypoxic conditions.",
keywords = "Cancer cells, Carbonic anhydrase, Castagnoli-cushman reaction, Hypoxic environment, In silico docking, Isoform-selective inhibitors, Periphery groups, Primary sulfonamides, Scaffold, Seed SAR, Subnanomolar inhibition, DESIGN, SULFONAMIDES, SULFOCHLORINATION, ASTROCYTES, POTENT, PROFILE, BENZENESULFONAMIDES, PICOMOLAR INHIBITORS, In silica docking, ISOFORMS I, CELL-LINE",
author = "Stanislav Kalinin and Alessio Nocentini and Alexander Kovalenko and Vladimir Sharoyko and Alessandro Bonardi and Andrea Angeli and Paola Gratteri and Tennikova, {Tatiana B.} and Supuran, {Claudiu T.} and Mikhail Krasavin",
year = "2019",
month = nov,
day = "15",
doi = "10.1016/j.ejmech.2019.111642",
language = "English",
volume = "182",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - From random to rational: A discovery approach to selective subnanomolar inhibitors of human carbonic anhydrase IV based on the Castagnoli-Cushman multicomponent reaction

AU - Kalinin, Stanislav

AU - Nocentini, Alessio

AU - Kovalenko, Alexander

AU - Sharoyko, Vladimir

AU - Bonardi, Alessandro

AU - Angeli, Andrea

AU - Gratteri, Paola

AU - Tennikova, Tatiana B.

AU - Supuran, Claudiu T.

AU - Krasavin, Mikhail

PY - 2019/11/15

Y1 - 2019/11/15

N2 - By exploiting the power of multicomponent chemistry, a relatively small, diverse set of primary sulfonamides was synthesized and screened against a panel of human carbonic anhydrases to reveal a low-nanomolar, albeit non-selective hCA IV lead inhibitor. Investigation of the docking poses of this compound identified a hydrophilic pocket unique to hCA IV and conveniently positioned near the carboxylate functionality of the initial lead. Various residues capable of forming hydrogen bonds as well as salt bridges were placed in this pocket via a carboxamides linkage, which led to drastic improvement of potency and selectivity towards hCA IV. This improvement of the desired inhibitory profile was rationalized by the new contacts as had been envisioned. These new tool compounds were shown to possess selective, dose-dependent cytotoxicity against human glioma T98G cell line. The latter showed a substantially increased hCA IV mRNA expression under hypoxic conditions.

AB - By exploiting the power of multicomponent chemistry, a relatively small, diverse set of primary sulfonamides was synthesized and screened against a panel of human carbonic anhydrases to reveal a low-nanomolar, albeit non-selective hCA IV lead inhibitor. Investigation of the docking poses of this compound identified a hydrophilic pocket unique to hCA IV and conveniently positioned near the carboxylate functionality of the initial lead. Various residues capable of forming hydrogen bonds as well as salt bridges were placed in this pocket via a carboxamides linkage, which led to drastic improvement of potency and selectivity towards hCA IV. This improvement of the desired inhibitory profile was rationalized by the new contacts as had been envisioned. These new tool compounds were shown to possess selective, dose-dependent cytotoxicity against human glioma T98G cell line. The latter showed a substantially increased hCA IV mRNA expression under hypoxic conditions.

KW - Cancer cells

KW - Carbonic anhydrase

KW - Castagnoli-cushman reaction

KW - Hypoxic environment

KW - In silico docking

KW - Isoform-selective inhibitors

KW - Periphery groups

KW - Primary sulfonamides

KW - Scaffold

KW - Seed SAR

KW - Subnanomolar inhibition

KW - DESIGN

KW - SULFONAMIDES

KW - SULFOCHLORINATION

KW - ASTROCYTES

KW - POTENT

KW - PROFILE

KW - BENZENESULFONAMIDES

KW - PICOMOLAR INHIBITORS

KW - In silica docking

KW - ISOFORMS I

KW - CELL-LINE

UR - http://www.scopus.com/inward/record.url?scp=85071486861&partnerID=8YFLogxK

U2 - 10.1016/j.ejmech.2019.111642

DO - 10.1016/j.ejmech.2019.111642

M3 - Article

AN - SCOPUS:85071486861

VL - 182

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

SN - 0223-5234

M1 - 111642

ER -

ID: 46203675