2-Phenyl substituted Benzimidazole derivatives: Design, synthesis, and evaluation of their antiproliferative and antimicrobial activities

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Ersan R. H., Kuzu B., Yetkin D., ALAGÖZ M. A., DÖĞEN A., BURMAOĞLU S., ...Daha Fazla

MEDICINAL CHEMISTRY RESEARCH, cilt.31, sa.7, ss.1192-1208, 2022 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 31 Sayı: 7
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1007/s00044-022-02900-3
  • Dergi Adı: MEDICINAL CHEMISTRY RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, Veterinary Science Database
  • Sayfa Sayıları: ss.1192-1208
  • Anahtar Kelimeler: Benzimidazole, Antiproliferative activity, Antimicrobial activity, SAR, Molecular docking, ADMET, BIOLOGICAL EVALUATION, BENZOXAZOLE
  • Atatürk Üniversitesi Adresli: Evet

Özet

The inability to meet the desired outcomes of anticancer treatment and decrease in treatment success of bacterial and fungal infections accelerated research in these areas. Our research group has conducted numerous studies, especially on benzimidazole ring systems' antiproliferative and antimicrobial activities. In this study, the antiproliferative activity of benzimidazole compounds was tested against A549, A498, HeLa, A375, and HepG2 cancer cell lines by MTT assay. All compounds exhibited good to potent antiproliferative activity against all tested cancer cell lines. Compounds 6-chloro-2-(4-fluorobenzyl)-1H-benzo[d] imidazole (30) and 6-chloro-2-phenethyl-1H-benzo[d]imidazole (46) were especially active against HeLa and A375 cancer cell lines with IC50 values in the range of 0.02-0.04 mu M. In contrast, compounds 6-chloro-2-((p-tolyloxy)methyl)-1H-benzo[d] imidazole (67) and 5(6)-chloro-2-((4-hydroxyphenoxy)methyl)-1H-benzimidazole (68) were active against A549 and A498 cancer cell lines with an IC50 value of 0.08 mu M. These compounds (30, 46, 67, and 68) were less toxic to normal human cells than the positive control compound methotrexate, which was screened to determine its toxicity against normal cell lines (HEK293). In the second part of the study, all compounds were tested to demonstrate their antimicrobial properties. All compounds exhibited moderate activity against all tested bacteria and fungi. However, some phenoxy methyl derivatives 5-chloro-2-((4-chlorophenoxy)methyl)-1H-benzo[d]imidazole (69) and 5,6-dichloro-2-((4-chlorophenoxy)methyl)-1H-benzo[d] imidazole and (74) were most active against Candida (<3.90 mu g/mL). Molecular docking studies were carried out against certain proteins in order to identify potential targets of the antiproliferative effects of the synthesized compounds. The docking scores of the compounds were found to be significantly compatible with the antiproliferative activity results.