Novel N-Substituted Isatin-Oxoindolin-1H-Benzo[D] Imidazole Fumarate as a New Class of JNK3 Inhibitor: Design, Synthesis, Molecular Modeling and its Biological Activity.

Abstract

Background: A direct synthesis of functionalized dimethyl fumarate derivatives of 2- (2-((E)-(2-oxoindolin-3-ylidene)methyl)-1H-benzo[d]imidazol-1-yl) is achieved via one-pot reaction involving 2-methyl-1H-benzo[d]imidazole and appropriate isatin in the presence of DMAD.

Methods: Conversely, this one-pot reaction furnished, upon conduction at 60 ° C, the 2-(2-((E)- (2-oxoindolin-3-ylidene)methyl)-1H-benzo[d]imidazol-1-yl) products. The biological activities were evaluated against JNK3 kinase. We chose to dock the compounds into the JNK3 binding site in order to comprehend the molecular underpinnings of the observed bioactivities.

Results: The structures of the synthesized compound adduct were evidenced from NMR and MS spectral data and further confirmed by single-crystal X-ray diffraction. The biological activities revealing that the introduction of an alkyl group at the 1-position of the isatin moiety produced JNK3 inhibitors with IC₅₀ values in the low micromolar range.

Conclusion: This study synthesized a unique compound using a three-component method. Compound 4d showed high antitumor activity (IC₅₀ = 6.5 μM) against JNK3 inhibitors, while compounds 4c, 4d, and 4f exhibited high selectivity. The research highlights the effectiveness of the one-pot reaction in creating medically useful hybrid compounds, marking a significant advance in medicinal chemistry.