Extending the Inhibition Profiles of Coumarin-Based Compounds Against Human Carbonic Anhydrases: Synthesis, Biological, and In Silico Evaluation

Extending the Inhibition Profiles of Coumarin-Based Compounds Against Human Carbonic Anhydrases: Synthesis, Biological, and In Silico Evaluation Научная публикация

Журнал

Molecules
ISSN: 1420-3049

Вых. Данные

Год: 2019, Том: 24, Номер: 19, Номер статьи : 3580, Страниц : DOI: 10.3390/molecules24193580

Авторы

Kartsev Victor ¹ , Geronikaki Athina ² , Bua Silvia ³ , Nocentini Alessio ³ , Petrou Anthi ² , Lichitsky Boris ⁴ , Frasinyuk Mykhaylo ⁵ , Leitans Janis ⁶ , Kazaks Andris ⁶ , Tars Kaspars ⁶ , Supuran Claudiu T. ³

Организации

1	InterBioscreen, 119019 Moscow, Russia
2	School of Health, Department of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
3	Dipartimento Neurofarba, Sezione Di Scienze Farmaceutiche e Nutraceutiche, Universita' Degli Studi Di Firenze, Sesto Fiorentino, 50019 Florence, Italy
4	Zelinsky Institute of Organic Chemistry, Leninsky prospect, 119991, Moscow, Russia
5	Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Science of Ukraine, 02094 Kiev, Ukraine
6	Latvian Biomedical Research and Study Center, Ratsupites 1, LV-1067 Riga, Latvia

Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the fundamental reaction of CO2 hydration in all living organisms and are actively involved in the regulation of a plethora of pathological and physiological conditions. A set of new coumarin/ dihydrocoumarin derivatives was here synthesized, characterized, and tested as human CA inhibitors. Their inhibitory activity was evaluated against the cytosolic human isoforms hCA I and II and the transmembrane hCA IX and hCA XII. Two compounds showed potent inhibitory activity against hCA IX, being more active or equipotent with the reference drug acetazolamide. Computational procedures were used to investigate the binding mode of this class of compounds within the active site of hCA IX and XII that are validated as anti-tumor targets.

Kartsev V. , Geronikaki A. , Bua S. , Nocentini A. , Petrou A. , Lichitsky B. , Frasinyuk M. , Leitans J. , Kazaks A. , Tars K. , Supuran C.T.
Extending the Inhibition Profiles of Coumarin-Based Compounds Against Human Carbonic Anhydrases: Synthesis, Biological, and In Silico Evaluation
Molecules. 2019. V.24. N19. 3580 . DOI: 10.3390/molecules24193580 WOS Scopus OpenAlex

≡ Web of science:	WOS:000496242300165
≡ Scopus:	2-s2.0-85072991345
≡ OpenAlex:	W2978430549