Oxidation of cyanobenzocycloheptatrienes: Synthesis, photooxygenation reaction and carbonic anhydrase isoenzymes inhibition properties of some new benzotropone derivatives

Murat Güney; Ahmet Coşkun; Fevzi Topal; Arif Daştan; Ilhami Gülçin; Claudiu T Supuran

doi:10.1016/j.bmc.2014.04.007

Oxidation of cyanobenzocycloheptatrienes: Synthesis, photooxygenation reaction and carbonic anhydrase isoenzymes inhibition properties of some new benzotropone derivatives

Bioorg Med Chem. 2014 Jul 1;22(13):3537-43. doi: 10.1016/j.bmc.2014.04.007. Epub 2014 May 2.

Authors

Murat Güney¹, Ahmet Coşkun², Fevzi Topal³, Arif Daştan⁴, Ilhami Gülçin⁵, Claudiu T Supuran⁶

Affiliations

¹ Ağri İbrahim Çeçen University, Faculty of Science and Art, Department of Chemistry, 04100 Agri, Turkey; Atatürk University, Faculty of Science, Department of Chemistry, 25240 Erzurum, Turkey. Electronic address: mguney@atauni.edu.tr.
² Konya Necmettin Erbakan University, Ahmet Keleşoglu Education Faculty, Department of Chemistry, 42099 Konya, Turkey. Electronic address: acoskun@konya.edu.tr.
³ Atatürk University, Faculty of Science, Department of Chemistry, 25240 Erzurum, Turkey; Gumushane University, Vocational School of Health Services, Department of Medical Services and Techniques, 29100 Gumushane, Turkey.
⁴ Atatürk University, Faculty of Science, Department of Chemistry, 25240 Erzurum, Turkey.
⁵ Atatürk University, Faculty of Science, Department of Chemistry, 25240 Erzurum, Turkey; King Saud University, Department Zoology, College of Science, Saudi Arabia. Electronic address: igulcin@atauni.edu.tr.
⁶ Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy. Electronic address: claudiu.supuran@unifi.it.

PMID: 24856184
DOI: 10.1016/j.bmc.2014.04.007

Abstract

The oxidation of some cyanocycloheptatrienes with CrO3 and pyridine was investigated and a few new nitrile functionalised benzotropone derivatives were obtained. Photooxygenation reaction of these products was also studied. The structures of the formed products were determined on the basis of NMR spectroscopy and the formation mechanism of unusual products was discussed. Human carbonic anhydrase isoenzymes I, and II (hCA I and hCA II) inhibition properties of nitrile functionalized new benzotropone derivatives were also studied. Both CA isozymes were inhibited in the low micromolar range by these nitrile functionalized benzotropone analogues. The newly synthesized benzotropone derivatives showed inhibition constants in the sub-micromolar range (2.51-4.06μM). The best hCA I inhibition was observed in 5H-benzocycloheptene-7-carbonitrile (Ki: 2.88±0.86μM). On the other hand, 5-oxo-5H-benzocycloheptatriene-7-carbonitrile showed the powerful inhibitory effect against hCA II (Ki: 2.51±0.34μM).

Keywords: Benzocycloheptatriene; Benzotropone; Carbonic anhydrase inhibition; Nitrile-substituted drugs; Oxidation; Rearrangement.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carbonic Anhydrase I / antagonists & inhibitors*
Carbonic Anhydrase I / metabolism
Carbonic Anhydrase II / antagonists & inhibitors*
Carbonic Anhydrase II / metabolism
Carbonic Anhydrase Inhibitors / chemical synthesis
Carbonic Anhydrase Inhibitors / chemistry
Carbonic Anhydrase Inhibitors / pharmacology*
Dose-Response Relationship, Drug
Humans
Isoenzymes / antagonists & inhibitors
Isoenzymes / metabolism
Models, Molecular
Molecular Structure
Oxidation-Reduction
Photochemical Processes
Structure-Activity Relationship
Tropolone / analogs & derivatives*
Tropolone / chemical synthesis
Tropolone / chemistry
Tropolone / pharmacology

Substances

Carbonic Anhydrase Inhibitors
Isoenzymes
Tropolone
tropone
Carbonic Anhydrase I
Carbonic Anhydrase II