Discovery of a Novel Series of Tetrahydro‐β‐carbolines Inducing Autophagic Cell Death in Human Metastatic Melanoma. Issue 6 (20th March 2014)

• Record Type: Journal Article
• Authors: Ahmed, Nermin S.; Elgendy, Mohamed; Laufer, Stefan; Abadi, Ashraf H.
• Is Part Of: Archiv der Pharmazie. Volume 347:Issue 6(2014:Jun.)
• Page Start: 398
• Page End: 406
• Publication Date: 2014-03-20
• Subjects: Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.201300437
• Languages: English
• ISSNs: 0365-6233

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ardp201300437-sec-0001" sec-type="section"> <p>Herein, we report the synthesis of novel tetrahydro‐β‐carbolines that induce cell death via the autophagic pathway. Five of the new compounds induced cell death in a panel of patient‐derived human metastatic melanoma cells. The autophagic pathway was confirmed using LC3 autophagosome markers; the involvement of ATG7 and Beclin 1 autophagy regulating genes was confirmed using infection with short hairpin RNA (shRNA) to silence Beclin 1 and ATG7. Compound <bold>VIII</bold> (IC₅₀ = 2.34–5.15 μM) displayed activities greater than cisplatin against a panel of patient‐derived human metastatic melanoma cell lines. The structure–activity relationship (SAR) of this class and the role of the absolute stereochemistry and geometrical isomerism are evaluated.</p> </sec> </abstract>