4.7 Article

Insights into the anticancer activity of chiral alkylidene-β-lactams and alkylidene-γ-lactams: Synthesis and biological investigation

Journal

BIOORGANIC & MEDICINAL CHEMISTRY
Volume 63, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2022.116738

Keywords

Alkylidene-beta-lactam; Alkylidene-gamma-lactam; Penicillanates; Anticancer agents; Melanoma; Esophageal cancer; Lung cancer; Fibrosarcoma

Funding

  1. Portuguese Agency for Scientific Research, Fundacao para a Ciencia e a Tecnologia (FCT) [UIDB/00313/2020, UIDP/00313/2020]
  2. COMPETE2020-UE
  3. FCT [UID/NEU/04539/2019, UIDB/04539/2020, UIDP/04539/2020, UIDB/50006/2020, UIDP/50006/2020, LA/P/0008/2020, UIDB/04378/2020, UIDP/04378/2020, LA/P/0140/2020, SFRH/BD/128910/2017]
  4. COMPETE-FEDER [POCI-01-0145-FEDER-007440]
  5. FCT-MCTES [RECI/BBB-BEP/0124/2012]
  6. Fundação para a Ciência e a Tecnologia [SFRH/BD/128910/2017] Funding Source: FCT

Ask authors/readers for more resources

Chiral alkylidene-beta-lactams and alkylidene-gamma-lactams were synthesized and screened for their potential anticancer activity against different human cancer cell lines.
Chiral alkylidene-beta-lactams and alkylidene-gamma-lactams were synthesized and screened for their in vitro activity against four human cancer cell lines (melanoma, esophageal, lung and fibrosarcoma carcinoma). Alkylidene-beta-lactams were synthesized via Wittig reaction of diverse phosphorus ylides with benzhydryl 6-oxopenicillanate, derived from 6-aminopenicillanic acid. Moreover, novel chiral alkylidene-gamma-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 mu M for A375 cell line, and three compounds with IC50 values < 10 mu M 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-beta-lactams as anticancer agents.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available