Discovery of Novel Fluorescent Azaindoles with Cytotoxic Action in A2780 Ovarian Carcinoma Cells

abstract

Azaindole scaffold is a privileged structure in medicinal chemistry and some derivatives have demonstrated to be potential anticancer drugs. Herein, a set of novel azaindoles, comprising the four regioisomers, bearing a morpholine (azaindoles 3 a-d) and N-methyl-N-benzylamine (azaindoles 4 a-d) groups were prepared. Among these compounds, azaindoles 4 exhibited higher cytotoxicity against the ovarian cancer cell line A2780 and normal dermal fibroblasts compared to azaindoles 3. Furthermore, azaindoles 4 b and 4 c promoted a delay in the cell cycle of the cancer cell line, inspiring an investigation into the intracellular localization of these derivatives. Azaindole derivatives bearing a morpholine and N-methyl-N-benzylamine moieties, demonstrated to be potential anticancer drugs, exhibiting cytotoxicity against the ovarian cancer cell line A2780 and normal dermal fibroblasts. Some derivatives also promoted a delay in the cell cycle of the cancer cell line, inspiring an investigation into the intracellular localization of these derivatives. image

keywords

7-AZAINDOLES; DERIVATIVES; ANTICANCER

subject category

Pharmacology & Pharmacy

authors

Cunha, JC; Roma-Rodrigues, C; Ferreira, JRM; Baptista, PV; Fernandes, AR; Guieu, S; Marques, MMB

Groups

G1 - Porous Materials and Nanosystems

Projects

CICECO - Aveiro Institute of Materials (UID/CTM/50011/2019)

CICECO - Aveiro Institute of Materials (UIDB/50011/2020)

CICECO - Aveiro Institute of Materials (UIDP/50011/2020)

Collaboratory for Emerging Technologies, CoLab (EMERGING TECHNOLOGIES)

acknowledgements

The authors thank the Fundacao para a Ciencia e Tecnologia (FCT, projects PTDC/QUI-QOR/0712/2020) and fellowship UI/BD/151272/2021 (J. R. M. F.). The authors also thank the support by the Laboratorio Associado para a Quimica Verde (LAQV), which is financed by national funds from FCT/Ministerio da Ciencia, Tecnologia e Ensino Superior FCT/MCTES (LA/P/0008/2020 DOI 10.54499/LA/P/0008/2020, UIDP/50006/2020 DOI 10.54499/UIDP/50006/2020 and UIDP/50006/2020 DOI 10.54499/UIDB/50006/2020), and the CICECO-Aveiro Institute of Materials (UID/CTM/50011/2019, UIDB/50011/2020 & UIDP/50011/2020). The National NMR Facility is supported by FCT, ROTEIRO/0031/2013-PINFRA/22161/2016, co-financed by FEDER through COMPETE 2020, POCI, and PORL and FCT through PID-DAC) and CERMAX (022162). This research was funded by the University of Aveiro, FCT/MEC, Centro 2020 and Portugal2020, and the COMPETE program. This work is financed by national funds from FCT - Fundacao para a Ciencia e a Tecnologia, I.P., in the scope of the project UIDP/04378/2020 (10.54499/UIDP/04378/2020) and UIDB/04378/2020 (10.54499/UIDB/04378/2020) of the Research Unit on Applied Molecular Biosciences - UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy - i4HB. C.R.-R. was funded by FCT/MCTES, grant number SFRH/BPD/124612/2016.