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Heterocoumarins Are Selective Carbonic Anhydrase IX and XII Inhibitors with Cytotoxic Effects against Cancer Cells Lines.

ABSTRACT: We have synthesized a new series of coumarin-based compounds demonstrating high selectivity and potent effects with low nanomolar affinity against the tumor associated carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA IX and XII. A number of these compounds were evaluated ex vivo against human prostate (PC3) and breast (MDA-MB-231) cancer cell lines. Compounds 4b and 15 revealed effective cytotoxic effects after 48 h of incubation in both normoxic and hypoxic conditions with PC3 cancer cell line. However, compound 3 showed selective cytotoxic effects against MDA-MB-231 in hypoxic condition. These results may be of particular importance for the choice of future drug candidates targeting hypoxic tumors and metastases, considering the fact that a selective carbonic anhydrase CA IX inhibitor (SLC-0111) is presently in phase II clinical trials.

SUBMITTER: Angeli A

PROVIDER: S-EPMC6142056 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Heterocoumarins Are Selective Carbonic Anhydrase IX and XII Inhibitors with Cytotoxic Effects against Cancer Cells Lines.

Angeli Andrea A Trallori Elena E Carta Fabrizio F Di Cesare Mannelli Lorenzo L Ghelardini Carla C Supuran Claudiu T CT

ACS medicinal chemistry letters 20180829 9

We have synthesized a new series of coumarin-based compounds demonstrating high selectivity and potent effects with low nanomolar affinity against the tumor associated carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA IX and XII. A number of these compounds were evaluated ex vivo against human prostate (PC3) and breast (MDA-MB-231) cancer cell lines. Compounds 4b and 15 revealed effective cytotoxic effects after 48 h of incubation in both normoxic and hypoxic conditions with ...[more]

PMID: 30258546

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