Multicomponent Synthesis, Crystal Structure, Hirshfeld Surface Analysis, and Molecular Docking of 4H‐Pyrans

Abstract

In this study, a series of four 4H-pyrans were synthesized by multicomponent reaction, crystallized, and single-crystal X-ray diffraction was used to obtain their molecular geometries. The supramolecular assembly of the molecules through noncovalent interactions was then studied and demonstrated. The weak intermolecular interactions in the molecular packing of compounds were further validated through Hirshfeld surface analysis. The synthesized compounds' biological activity was predicted in Pass prediction. A molecular docking study was employed to validate its activity by analyzing its binding affinity and mode in the binding pocket of the beta-adrenoreceptors (β 1 -AR and β 2 -AR). Results showed that ethyl 6-amino-5-cyano-2-methyl-4-(2-nitrophenyl)-4H-pyran-3-carboxylate have good antiischemic activity and binding affinity to both the adrenoreceptors. This study further demonstrated the importance of non-covalent intermolecular interactions of 4H-pyrans in the formation of supramolecular self-assembly and contributions of weak interactions in binding affinity towards the target receptor. The studied compounds displayed distinctive intermolecular interactions of NÀ H…N, NÀ H…O hydrogen-bonding patterns and CÀ H…π and π…π close contact interactions.

Non‐Covalent Interactions in the Self‐Assembly of Dihydropyridone Supramolecules and In Vitro Anti‐Cancer Assessment in Human Lung Adenocarcinoma Cell Line (A549)

“…The mixture was then stirred using magnetic stirrer for 10 min at room temperature. The precipitate was filtered in a sintered glass funnel, washed with ice‐cold methanol, and then kept in a desiccator to obtain a pure product of 4H‐pyran derivatives [20,21] …”

“…In the present study, a new series of cyanopyridine-based dihydropyridones derivatives are synthesized. Motivated from our previous research, [2,[19][20][21] pyran derivatives bearing anisole and toluene moieties are converted to pyridone derivates in the current research. However, three pyran derivatives with 3-OCH 3 , 4-NO 2 , 2,5-OCH 3 possessing phenyl groups connected to the central pyran ring were not selected for this present study.…”

“…Apart from the supramolecular framework, we also aimed to explore the role of non‐covalent interactions in anticancer activity and evaluate anticancer activity through in vitro using human lung adenocarcinoma (A549). It has been recently identified that calcium channels are potential targets for cancer therapy [19,20] . Similarly, PDE3 enzymes are overexpressed in many cancer cells [21] .…”

Synthesis of a Pyridone-Based Phthalimide Fleximer and Its Characterization and Supramolecular Property Evaluation

“… 3 , 22 Understanding these forces is also important for solid-state materials with desirable properties in supramolecular chemistry. 3 , 23 …”

“…Generally, noncovalent interactions refer to hydrogen bonds; − halogen bonds; , ionic bonds; − and weak interactions such as van der Waals, hydrophobic, , aromatic π–stacking interactions, and so forth. , These powerful driving forces lead to diverse interactions between molecules such as hydrogen bonds of the types O–H···O, N–H···O, C–H···N, and C–H···O and other weaker interactions of the types I···I, O···I, N···Cl, C···H, C···C, and so forth . Furthermore, C–H···lp (lone pair), C–H···π, and π···π interactions also act as cohesive forces in the supramolecular assembly of molecules. , Understanding these forces is also important for solid-state materials with desirable properties in supramolecular chemistry. , …”