Design, synthesis and molecular docking studies of novel benzimidazole-1,3,4-oxadiazole hybrids for their carbonic anhydrase inhibitory and antioxidant effects


Kucukoglu K., ÇEVİK U. A., NADAROĞLU H., ÇELİK İ., Isik A., BOSTANCI H. E., ...Daha Fazla

MEDICINAL CHEMISTRY RESEARCH, cilt.31, sa.10, ss.1771-1782, 2022 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 31 Sayı: 10
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1007/s00044-022-02943-6
  • 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.1771-1782
  • Anahtar Kelimeler: Benzimidazole, 1, 3, 4-Oxadiazole, Carbonic anhydrase, Molecular Docking, Antioxidant, MICROWAVE-ASSISTED SYNTHESIS, ISOENZYMES HCA I, SCHIFF-BASES, DERIVATIVES, VITRO, 1,3,4-OXADIAZOLE, SULFONAMIDES, ANALOGS, CELLS, ACID
  • Atatürk Üniversitesi Adresli: Evet

Özet

In this study, eleven new compounds with a series of benzimidazole-1,3,4-oxadiazole derivatives structures were synthesized and evaluated for their human (h) carbonic anhydrase inhibitory activities against two isoforms hCA I, hCA II, and antioxidant activity. The synthesized compounds were fully characterized by spectral analysis methods such as H-1-NMR, C-13-NMR, and HRMS. Compared to acetazolamide (IC50 = 2.26 mu M) for hCA I, the most potent compound 4a was with the IC50 value of 1.322 mu M and compound 4d is the other molecule with a greater IC50 value (IC50 = 1.989 mu M) than that of acetazolamide in these series. Among all the compounds, 4a (1.826 mu M), 4d (1.502 mu M), and 4g (1.886 mu M) are the most active hybrids against carbonic hCA II. Considering that compound 4a containing 4-bromophenyl structure is effective on both hCA I and hCA II, it can be considered as a promising structure for the development of effective candidates with potent CA inhibitory activities. TAS assay was used to evaluate the antioxidant activities of synthesized compounds. The synthesized compound was analyzed for their in vitro cytotoxic activity on the L929 cell line by using MTT assay. In the last step of this study, molecular docking studies were performed in order to compare the biological activities of the most active molecules against the enzymes of hCAI and hCA II.