Bimetallic Pd-Ni anchored cellulose supported-MOF catalyzed synthesis of cinnamyloxy-linked azepinone derivatives targeting the PARP enzyme: molecular docking validation.

This article discloses the fabrication of a bimetallic Pd-Ni-anchored cellulose-supported metal-organic framework, i.e., Pd-Ni@NH2-BDC-Fe@RH-CNC, where RH-CNC was derived from agro-waste rice husk. The fabricated catalyst was used to synthesize cinnamyloxy derivatives from dimedone via a sequential one-pot Heck coupling reaction. To assess the catalyst's efficacy, the reaction was studied using a series of substrates, revealing excellent product yields and remarkable catalytic cycles. The cinnamyloxy intermediate 5a was further explored for the synthesis of cinnamyloxy-linked azepinone derivatives 7(a-i)via Beckmann rearrangement. The biological efficacy of 7(a-i) was confirmed by molecular docking studies; the results indicated that cinnamyloxy-linked azepinone, particularly 7h (140 kcal mol-1), showed favorable binding interaction with the active site of the PARP enzyme, suggesting promising hit molecules for further evaluation of anticancer potential. Conclusively, the present catalytic methodology has broad applicability for the construction of biologically relevant heterocycles.