BIENTA at 7th International Conference on Drug Discovery and Therapy

We will be paricipating in the 7th International Conference on Drug Discovery and Therapy (ICDDT), Sharjah, UAE, February 15th – 18th, 2016.

Poster: Dubai CA 2016 Poster

Discovery of Strecker-Type Aminonitriles as a New Class of Human Carbonic Anhydrase Inhibitors Using Differential Scanning Fluorimetry

Roman Stavniichuk,a Sergey Zozulya,a Petro Borysko, a Daniela Vullo,b Claudiu T. Supuran,b and Mikhail Krasavinc

a Enamine Ltd/Bienta, 78 Chervonotkatska, Kyiv 02094, Ukraine

b Neurofarba Dept., Universita degli Studi di Firenze, Florence, Italy

c Institutes of Chemistry and Translational Biomedicine, Saint Petersburg State University, Russian Federation


Carbonic anhydrase inhibitors (CAIs) are widely used in the clinic as diuretic and antiglaucoma (intraocular pressure-lowering) agents. However, new applications of isoform-selective CAIs have emerged, particularly in oncology. Identification of new chemotypes outside of the primary sulfonamide chemistry space (where the majority of known CAIs reside) can open new opportunities for designing such inhibitors.

Herein, we report a serendipitous discovery of hitherto not reported class of CAIs via differential scanning fluorimetry (DSF, Thermal Shift Assay) screening of an unbiased, diverse set of compounds against bovine carbonic anhydrase. The compounds, all of which are a-aminonitriles attainable by the Strecker reaction, displayed modest (DTm = 1.0-1.8 °C) thermal shifts compared to the known and clinically used CAI acetazolamide (DTm = 5.0 °C). The compounds were further advanced to biochemical testing against a panel of human carbonic anhydrases (hCAI, hCAII, hCAIX and hCAXII) and showed submicromolar inhibition of certain isoforms with an apparent selectivity pattern. In this Communication, we provide preliminary insight into a possible inhibitory mechanism displayed by these compounds.