Benzimidazolone-piperazine/triazole/thiadiazole/furan/thiophene conjugates: Synthesis, in vitro urease inhibition, and in silico molecular docking studies

Güven O., MENTEŞE E., EMİRİK M., Sökmen B. B., AKYÜZ G.

ARCHIV DER PHARMAZIE, cilt.356, sa.11, 2023 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 356 Sayı: 11
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1002/ardp.202300336
  • Dergi Adı: ARCHIV DER PHARMAZIE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, International Pharmaceutical Abstracts, Veterinary Science Database
  • Anahtar Kelimeler: benzimidazolone, heterocyclic, molecular docking, urease inhibition
  • Recep Tayyip Erdoğan Üniversitesi Adresli: Evet

Özet

This study describes the synthesis, in vitro urease inhibition, and molecular docking studies of benzimidazolone derivatives incorporating the piperazine, triazole, thiadiazole, furan, thiophene, and thiosemicarbazide moieties. All newly synthesized compounds demonstrated varying degrees of urease inhibitory activity, with IC50 values ranging between 0.64 ± 0.099 and 0.11 ± 0.017 µM, when compared with the standard drug thiourea (IC50 value of 0.51 ± 0.028 µM). To confirm the experimental urease inhibition results and elucidate the mode of interaction of the synthesized compounds with the binding site of the urease enzyme, molecular docking studies were performed using the Schrödinger Suite package. Molecular docking studies showed that compounds with high in vitro urease inhibition interacted with key residues of the urease active site such as His221, Glu222, Asp223, His322, Arg338, and Ni2+ cations via hydrogen bonding, metal coordination, salt bridge, π–π stacking, and π–cation interactions.