Synthesis and Crystal Structure of Adamantylated 4,5,6,7-Tetrahalogeno-1H-benzimidazoles Novel Multi-Target Ligands (Potential CK2, M2 and SARS-CoV-2 Inhibitors); X-ray/DFT/QTAIM/Hirshfeld Surfaces/Molecular Docking Study.
Molecules
; 28(1)2022 Dec 24.
Article
in English
| MEDLINE | ID: covidwho-2242509
ABSTRACT
A series of new congeners, 1-[2-(1-adamantyl)ethyl]-1H-benzimidazole (AB) and 1-[2-(1-adamantyl)ethyl]-4,5,6,7-tetrahalogeno-1H-benzimidazole (Hal=Cl, Br, I; tClAB, tBrAB, tIAB), have been synthesized and studied. These novel multi-target ligands combine a benzimidazole ring known to show antitumor activity and an adamantyl moiety showing anti-influenza activity. Their crystal structures were determined by X-ray, while intermolecular interactions were studied using topological Bader's Quantum Theory of Atoms in Molecules, Hirshfeld Surfaces, CLP and PIXEL approaches. The newly synthesized compounds crystallize within two different space groups, P-1 (AB and tIAB) and P21/c (tClAB and tBrAB). A number of intramolecular hydrogen bonds, C-Hâ¯Hal (Hal=Cl, Br, I), were found in all halogen-containing congeners studied, but the intermolecular C-Hâ¯N hydrogen bond was detected only in AB and tIAB, while C-Halâ¯π only in tClAB and tBrAB. The interplay between C-Hâ¯N and C-Hâ¯Hal hydrogen bonds and a shift from the strong (C-Hâ¯Cl) to the very weak (C-Hâ¯I) attractive interactions upon Hal exchange, supplemented with Halâ¯Hal overlapping, determines the differences in the symmetry of crystalline packing and is crucial from the biological point of view. The hypothesis about the potential dual inhibitor role of the newly synthesized congeners was verified using molecular docking and the congeners were found to be pharmaceutically attractive as Human Casein Kinase 2, CK2, inhibitors, Membrane Matrix 2 Protein, M2, blockers and Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV-2, inhibitors. The addition of adamantyl moiety seems to broaden and modify the therapeutic indices of the 4,5,6,7-tetrahalogeno-1H-benzimidazoles.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
SARS-CoV-2
/
COVID-19
Type of study:
Experimental Studies
/
Randomized controlled trials
Topics:
Variants
Limits:
Humans
Language:
English
Journal subject:
Biology
Year:
2022
Document Type:
Article
Affiliation country:
Molecules28010147
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