Structural modification of naturally occurring phenolics as a strategy for developing cytotoxic molecules towards cancer cells

• Type: Article in International Scientific Journal
• Date: 2023

Authors

Olim, P (Author) Other; Pereira, RB (Author) Other; Fernandes, MJG (Author) Other; Natal, CM (Author) Other; Coelho, JRA (Author) Other; Fortes, AG (Author) Other; Gonçalves, MST (Author) Other; David M Pereira (Author) FFUP

Journal

Title: Archiv der Pharmazie

Vol. 356

ISSN: 0365-6233

Publisher: Wiley-Blackwell

Indexing

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Other information

Authenticus ID: P-00Z-5S7

DOI: 10.1002/ardp.202300294

Abstract (EN): Natural products belonging to different chemical classes have been established as a promising source of novel anticancer drugs. Several low-molecular-weight compounds from the classes of monoterpenes, phenylpropanoids, and flavonoids were shown to possess anticancer activities in previous studies. In this work, over 20 semisynthetic derivatives of molecules belonging to these classes, namely thymol, eugenol, and 6-hydroxyflavanone were synthesized and tested for their cytotoxicity against two human cancer cell lines, namely AGS cells (gastric adenocarcinoma) and A549 cells (human lung carcinoma). An initial screening based on viability assessment was performed to identify the most cytotoxic compounds at 100 mu M. The results evidenced that two 6-hydroxyflavanone derivatives were the most cytotoxic among the compounds tested, being selected for further studies. These derivatives displayed enhanced toxicity when compared with their natural counterparts. Moreover, the lactate dehydrogenase (LDH) assay showed that the loss of cell viability was not accompanied by a loss of membrane integrity, thus ruling out a necrotic process. Morphological studies with AGS cells demonstrated chromatin condensation compatible with apoptosis, confirmed by the activation of caspase 3/7. Furthermore, a viability assay on a noncancer human embryonic lung fibroblast cell line (MRC-5) confirmed that these two derivatives possess selective anticancer activity. Derivatives of naturally occurring phenolics were synthesized and evaluated for their cytotoxic activity toward cancer cells. Two 6-hydroxyflavanone derivatives showed enhanced cytotoxicity against gastric adenocarcinoma and lung carcinoma cells.image

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13