2. Academic Validation
  3. Synthesis, cytotoxic activity evaluation and mechanistic investigation of novel 3,7-diarylsubstituted 6-azaindoles

Synthesis, cytotoxic activity evaluation and mechanistic investigation of novel 3,7-diarylsubstituted 6-azaindoles

  • Eur J Med Chem. 2023 Sep 13:261:115804. doi: 10.1016/j.ejmech.2023.115804.
Nikolaos Lougiakis 1,  Nikolaos Sakalis 2,  Maria Georgiou 2,  Panagiotis Marakos 2,  Nicole Pouli 2,  Alexios-Leandros Skaltsounis 3,  Eleni Mavrogonatou 4,  Harris Pratsinis 4,  Dimitris Kletsas 4
Affiliations

Affiliations

  • 1 Division of Pharmaceutical Chemistry, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771, Athens, Greece. Electronic address: [email protected].
  • 2 Division of Pharmaceutical Chemistry, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771, Athens, Greece.
  • 3 Division of Pharmacognosy and Natural Products Chemistry, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771, Athens, Greece.
  • 4 Laboratory of Cell Proliferation and Ageing, Institute of Biosciences and Applications, NCSR ''Demokritos'', 15310, Athens, Greece.
PMID: 37729693 DOI: 10.1016/j.ejmech.2023.115804
Abstract

A number of new disubstituted 6-azaindoles have been designed and synthesized bearing a crucial structural modification in respect to an analogous antiproliferative hit compound. The synthesis was performed using 2-amino-3-nitro-4-picoline, that was suitably modified and converted to 7-chloro-3-iodo-6-azaindole and this central scaffold was used for successive Suzuki-type couplings, to result in the target compounds. The evaluation of the cytotoxic activity was performed against four human Cancer cell lines, as well as a normal human fibroblast strain. Certain compounds possessed strong Anticancer activity without affecting normal cells. At subcytotoxic concentrations for Cancer cells, these compounds displayed an anti-proliferative effect by arresting the cells at the G2/M phase of the cell cycle, which could be associated with the observed decrease in the phosphorylation levels of the MEK1- ERK1/2 pathway and/or the activation of the p53-p21WAF1 axis.

Keywords

Antiproliferative; Cell cycle arrest; Purine; Pyrrolopyridine; Selectivity; Suzuki-type coupling.

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