Enriching the Arsenal of Pharmacological Tools against MICAL2

Molecules. 2021 Dec 11;26(24):7519. doi: 10.3390/molecules26247519.

Abstract

Molecule interacting with CasL 2 (MICAL2), a cytoskeleton dynamics regulator, are strongly expressed in several human cancer types, especially at the invasive front, in metastasizing cancer cells and in the neo-angiogenic vasculature. Although a plethora of data exist and stress a growing relevance of MICAL2 to human cancer, it is worth noting that only one small-molecule inhibitor, named CCG-1423 (1), is known to date. Herein, with the aim to develop novel MICAL2 inhibitors, starting from CCG-1423 (1), a small library of new compounds was synthetized and biologically evaluated on human dermal microvascular endothelial cells (HMEC-1) and on renal cell adenocarcinoma (786-O) cells. Among the novel compounds, 10 and 7 gave interesting results in terms of reduction in cell proliferation and/or motility, whereas no effects were observed in MICAL2-knocked down cells. Aside from the interesting biological activities, this work provides the first structure-activity relationships (SARs) of CCG-1423 (1), thus providing precious information for the discovery of new MICAL2 inhibitors.

Keywords: 786-O kidney cancer cells; CCG-1423; HMEC-1 endothelial cells; MICAL2; Passerini 3-CR reaction; Passerini-like 3-CR; metastasis; multicomponent reactions (MCRs); neoangiogenesis; wound healing assay.

MeSH terms

  • Anilides* / chemistry
  • Anilides* / pharmacology
  • Benzamides* / chemistry
  • Benzamides* / pharmacology
  • Enzyme Inhibitors* / chemistry
  • Enzyme Inhibitors* / pharmacology
  • Humans
  • Microfilament Proteins* / antagonists & inhibitors
  • Microfilament Proteins* / metabolism
  • Molecular Structure
  • Oxidoreductases* / antagonists & inhibitors
  • Oxidoreductases* / metabolism
  • Small Molecule Libraries* / chemistry
  • Small Molecule Libraries* / pharmacology

Substances

  • Anilides
  • Benzamides
  • CCG 1423
  • Enzyme Inhibitors
  • MICAL2 protein, human
  • Microfilament Proteins
  • Oxidoreductases
  • Small Molecule Libraries