Exploring the potency of diazo-coumarin containing hybrid molecules: Selective inhibition of tumor-associated carbonic anhydrase isoforms IX and XII


Yapar G., Lolak N., Bonardi A., Akocak S., Supuran C. T.

ChemMedChem, vol.19, no.4, 2024 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 19 Issue: 4
  • Publication Date: 2024
  • Doi Number: 10.1002/cmdc.202300626
  • Journal Name: ChemMedChem
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Agricultural & Environmental Science Database, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE
  • Keywords: Cancer, Coumarin, Diazo, Hybrid molecules, Selective inhibitor
  • Istanbul Technical University Affiliated: Yes

Abstract

This study introduces a series of ten hybrid molecules DK(1-10), which combine diazo and coumarin moieties along with diverse aromatic substitutions. The primary objective was to evaluate the inhibitory capabilities of these compounds against four prominent isoforms: the cytosolic hCA I and II, as well as the tumor-associated membrane-bound hCA IX and XII. Impressively, the majority of the tested compounds exhibited significant inhibition activity against the tumor-associated isoforms hCA IX and XII, with KI values ranging from 29.2 to 293.3 nM. Notably, compound DK-8 displayed particularly robust inhibitory activity against the tumor-associated membrane-bound isoforms, hCA IX and XII, yielding KI values of 32.5 and 29.2 nM, respectively. Additionally, another derivative, DK-9, containing a primary sulfonamide, exhibited notable inhibition against hCA XII with a KI value of 36.4 nM. This investigation aimed to explore the structure-activity relationships within these compounds, shedding light on how various substitutions and structural components influence their inhibitory potential. As a result, these compounds present promising candidates for further exploration in medicinal and pharmacological research. Their ability to selectively inhibit specific isoforms, particularly those associated with hypoxic tumors, suggests their potential as foundational compounds for the development of novel therapeutic agents.