Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/107426
Title: Insights into the anticancer activity of chiral alkylidene-β-lactams and alkylidene-γ-lactams: Synthesis and biological investigation
Authors: Alves, Américo J. S. 
Alves, Nuno G. 
Laranjo, Mafalda 
Gomes, Clara S. B. 
Gonçalves, Ana Cristina 
Ribeiro, Ana Bela Sarmento 
Botelho, M. Filomena 
Pinho e Melo, Teresa M. V. D. 
Keywords: Alkylidene-β-lactam; Alkylidene-γ-lactam; Anticancer agents; Esophageal cancer; Fibrosarcoma; Lung cancer; Melanoma; Penicillanates
Issue Date: 1-Jun-2022
Publisher: Elsevier
Project: LA/P/0008/2020 
LA/P/0140/2020 
info:eu-repo/grantAgreement/FCT/3599-PPCDT/RECI/BBB-BEP/0124/2012/PT/Modern Structural Biology: Resources for the advancement of in-house X-ray Crystallography 
info:eu-repo/grantAgreement/FCT/OE/SFRH/BD/128910/2017/PT/Novel spiro-lactams as new antimicrobial agents 
info:eu-repo/grantAgreement/UIDP/04539/2020 
UIDB/50006/2020 
UIDP/50006/2020 
UIDB/04378/2020 
UIDB/04539/2020 
UIDB/00313/2020 
UIDP/00313/2020 
UIDP/04378/2020 
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID/NEU/04539/2019/PT 
Serial title, monograph or event: Bioorganic & Medicinal Chemistry
Volume: 63
Abstract: Chiral alkylidene-β-lactams and alkylidene-γ-lactams were synthesized and screened for their in vitro activity against four human cancer cell lines (melanoma, esophageal, lung and fibrosarcoma carcinoma). Alkylidene-β-lactams were synthesized via Wittig reaction of diverse phosphorus ylides with benzhydryl 6-oxopenicillanate, derived from 6-aminopenicillanic acid. Moreover, novel chiral alkylidene-γ-lactams were synthesized through a multistep strategy starting from a chiral substrate (d-penicillamine). The in vitro assays allowed the identification of four compounds with IC50 values < 10 μM for A375 cell line, and three compounds with IC50 values < 10 μM for OE19 cell line. The effect of the most promising compounds on cell death mechanism, reactive oxygen species generation as well as the evaluation of their ability to act as MMP-9 inhibitors were studied. The reported results unveil the potential of alkylidene-β-lactams as anticancer agents.
URI: https://hdl.handle.net/10316/107426
ISSN: 09680896
DOI: 10.1016/j.bmc.2022.116738
Rights: embargoedAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais
I&D CIBB - Artigos em Revistas Internacionais
I&D ICBR - Artigos em Revistas Internacionais
I&D CQC - Artigos em Revistas Internacionais

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