The Anticancer Activity for the Bumetanide-Based Analogs via Targeting the Tumor-Associated Membrane-Bound Human Carbonic Anhydrase-IX Enzyme.

ABSTRACT: The membrane-bound human carbonic anhydrase (hCA) IX is widely recognized as a marker of tumor hypoxia and a prognostic factor within several human cancers. Being undetected in most normal tissues, hCA-IX implies the pharmacotherapeutic advent of reduced off-target adverse effects. We assessed the potential anticancer activity of bumetanide-based analogues to inhibit the hCA-IX enzymatic activity and cell proliferation of two solid cancer cell lines, namely kidney carcinoma (A-498) and bladder squamous cell carcinoma (SCaBER). Bumetanide analogues efficiently inhibit the target hCA-IX in low nanomolar activity (IC₅₀ = 4.4-23.7 nM) and have an excellent selectivity profile (SI = 14.5-804) relative to the ubiquitous hCA-II isoform. Additionally, molecular docking studies provided

SUBMITTER: Malebari AM 

PROVIDER: S-EPMC7558282 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature