Bisbenzimidazole salts and their in silico-in vitro inhibitory abilities on hCA I, hCA II, and AChE enzymes

Eight new bisbenzimidazolium halides were prepared from alkyl halides and 4,4 '-bis[(benzimidazol-1-yl)methyl]-1,1 '-biphenyl.The structures of the benzimidazole salts were characterized using elemental analysis techniques as well as 1H, 13C NMR, and FT-IR spectroscopic methods. The inhibitory effects of the benzimidazole derivatives were measured against human carbonic anhydrase I (hCA I), human carbonic anhydrase II (hCA II), and acetylcholinesterase (AChE) enzymes. All benzimidazolium halides exhibited significant enzyme inhibitory properties. They showed highly potent inhibitory effect on AChE and hCAs (Ki values are in the range of 15.7 +/- 0.8 to 49.7 +/- 10.1 nM, 14.6 +/- 1.5 to 70.7 +/- 2.7 nM, and 17.4 +/- 2.8 to 38 +/- 10 nM for AChE, hCA I, and hCA II, respectively). The binding orientation of the synthesized bisbenzimidazolium halides was evaluated by molecular docking studies, reflecting the importance of the p-methylbenzyl, m-methylbenzyl, p-nitrophenethyl, and 3-(1,3-dioxoisoindolin-2-yl)methyl) groups in protein-ligand interaction. The docking results support the Ki values of the respective compounds in this study. The structure-activity relationships against the various targets are clearly shown in three dimensions at the atomic level by their interactions with the mentioned enzymes.

Dergi

MONATSHEFTE FUR CHEMIE

Yıl

2024

Cilt

155

Sayı

6

Sayfa

653-662

ISSN

0026-9247

eISSN

1434-4475

DOI

10.1007/s00706-024-03204-5

WoS UID

WOS:001220844700002