Blue LED Induced Three Component Reactions for the Generation of 4,6‐Dioxo‐hexahydro‐1H‐furo[3, 4‐c] pyrrole: Their Evaluation as Anticancer Agents through PARP‐1 Inhibition

• Published in: Chemistry, an Asian journal Vol. 18; no. 15; pp. e202300420 - n/a
• Main Authors: Khan, Haya, Guha, Souvik, Baruah, Mousumi, Yadav, Shalini, Maheshwari, Sanjana, Sainani, Sara, Maiti, Debajit, Sen, Subhabrata
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.08.2023
• Subjects: [3+2] Cycloaddition; Aldehydes; Anticancer properties; Antineoplastic Agents - pharmacology; Blue LED; Carbonyls; Cell Line, Tumor; Cell Proliferation; Chemical synthesis; Chemistry; Cycloaddition; Flow Chemistry; In-silico Studies; Molecular docking; Molecular Docking Simulation; PARP-1 Inhibition; Poly(ADP-ribose) Polymerase Inhibitors - pharmacology; Pyrroles - pharmacology; Ribose; Screening; Structure-Activity Relationship; Blue LED; PARP-1 Inhibition; [3+2] Cycloaddition; In-silico Studies; Flow Chemistry
• ISSN: 1861-4728; 1861-471X
• DOI: 10.1002/asia.202300420

Herein we report a catalyst, metal and additive free generation of carbonyl ylides by blue LED irradiation of aryl diazoacetates in presence of aldehydes. The resulting ylides underwent [3+2] cycloaddition with substituted maleimides present in the reaction mixture to afford 4, 6‐dioxo‐hexahydro‐1H‐furo[3, 4‐c] pyrrole in excellent yields. Fifty compounds were synthesized based on this scaffold. Molecular docking indicated them to be potential poly ADP ribose polymerase (PARP) inhibitor. Screening a representative member of the library against PARP‐1 enzyme revealed a few potential inhibitors with IC50 of 600–700 nM. The phenotypic screening against MCF7, A549 and HepG2 cells furthermore indicated that these compounds selectively inhibit the proliferation of A549, HeLa and HepG2 cells with IC50 of 1–2 μM. The mechanism of action of the most active compound at the cellular level was investigated. Blue LED induced carbonyl ylide formation, their 1, 3‐cycloaddition to a generate 4, 6‐dioxo‐hexahydro‐1H‐furo[3, 4‐c] pyrroles as potential PARP inhibitors.