Aryl azole derivatives as potential disruptors of tumor microenvironment

Thirty-nine aryl azoles, were synthesised and biologically evaluated for their activity as tumour microenvironment disruptors. Antiproliferative studies were performed in the tumour cell lines HT-29, A- 549 and MCF-7 and in the non-tumour cell line HEK-293. In HT-29, expression levels of biological targets involved in tumour microenvironment processes such as PD-L1, CD-47, c-Myc and VEGFR-2 were assessed. In addition, the antiproliferative activity was assessed when HT-29 were co-cultured with THP-1 monocytes and the secretion levels of IL-6 were also determined in these co-cultures. The angiogenic effect of some selected compounds on HMEC-1 was also evaluated as well as their effect on vasculogenic mimicry on HEK-293. Compounds with an amino group in the phenyl ring and a halogen atom in the benzyl ring showed promising results as tumour microenvironment disrupting agents. The most outstanding compound dramatically reduced the population of HT-29 cells when co-cultured with THP-1 monocytes and the levels of IL-6 secreted, as well as showing moderate effects on PD-L1, CD-47 and c-Myc.
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• Those people in the audience involved in Drug Discovery research could use most of the information we are going to provide.
• This is a multidisciplinary and interdisciplinary work so people from research fields involved in Medicinal Chemistry, Biochemistry, Organic Chemistry, Cell biology, Immunology could be interested.
• The audience will learn more about multitarget anticancer drug discovery for oncoimmunomodulating therapies.