Unravelling the anticancer potential of functionalized chromeno[2,3-b]pyridines for breast cancer treatment

Sofia Oliveira-Pinto; Olívia Pontes; Diogo Lopes; Belém Sampaio-Marques; Marta D Costa; Luísa Carvalho; Céline S Gonçalves; Bruno M Costa; Patrícia Maciel; Paula Ludovico; Fátima Baltazar; Fernanda Proença; Marta Costa

doi:10.1016/j.bioorg.2020.103942

Unravelling the anticancer potential of functionalized chromeno[2,3-b]pyridines for breast cancer treatment

Bioorg Chem. 2020 Jul:100:103942. doi: 10.1016/j.bioorg.2020.103942. Epub 2020 May 17.

Affiliations

¹ Life and Health Sciences Research Institute (ICVS), University of Minho, Campus of Gualtar, Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
² Department of Chemistry, University of Minho, Campus of Gualtar, Braga, Portugal.
³ Department of Chemistry, University of Minho, Campus of Gualtar, Braga, Portugal. Electronic address: fproenca@quimica.uminho.pt.
⁴ Life and Health Sciences Research Institute (ICVS), University of Minho, Campus of Gualtar, Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal. Electronic address: martafcosta@med.uminho.pt.

PMID: 32450388
DOI: 10.1016/j.bioorg.2020.103942

Abstract

A selection of new chromeno[2,3-b]pyridines was prepared from chromenylacrylonitriles and N-substituted piperazines, using a novel and efficient synthetic procedure. The compounds were tested for their anticancer activity using breast cancer cell lines MCF-7, Hs578t and MDA-MB-231 and the non-neoplastic cell line MCF-10A for toxicity evaluation. In general, compounds showed higher activity towards the luminal breast cancer subtype (MCF-7), competitive with the reference compound Doxorubicin. The in vivo toxicity assay using C. elegans demonstrated a safe profile for the most active compounds. Chromene 3f revealed a promising drug profile, inhibiting cell growth and proliferation, inducing cell cycle arrest in G₂/M phase, apoptosis and microtubule destabilization. The new compounds presented exciting bioactive features and may be used as lead compounds in cancer related drug discovery.

Keywords: Anticancer activity; Breast cancer; C. elegans; Chromeno[2,3-b]pyridine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology
Apoptosis / drug effects
Benzopyrans / chemical synthesis
Benzopyrans / chemistry*
Benzopyrans / pharmacology
Breast Neoplasms / metabolism
Breast Neoplasms / pathology
Caenorhabditis elegans / drug effects
Caenorhabditis elegans / physiology
Cell Line, Tumor
Cell Proliferation / drug effects
Doxorubicin / pharmacology
Drug Screening Assays, Antitumor
Female
G2 Phase Cell Cycle Checkpoints / drug effects
Humans
M Phase Cell Cycle Checkpoints / drug effects
Pyrimidines / chemical synthesis
Pyrimidines / chemistry*
Pyrimidines / pharmacology
Structure-Activity Relationship

Substances

Antineoplastic Agents
Benzopyrans
Pyrimidines
chromeno(2,3-b)-pyrimidine
Doxorubicin