Synthesis, characterization, anti-tuberculosis activity and molecular modeling studies of thiourea derivatives bearing aminoguanidine moiety

Tapera M., Kekecmuhammed H., Sahin K., Krishna V. S., Lherbet C., Homberset H., ...Daha Fazla

JOURNAL OF MOLECULAR STRUCTURE, cilt.1270, 2022 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 1270
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1016/j.molstruc.2022.133899
  • Dergi Adı: JOURNAL OF MOLECULAR STRUCTURE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, INSPEC
  • Anahtar Kelimeler: Synthesis, Thiourea, Tuberculosis, Computational investigations, InhA, FREE-ENERGY, HYDRAZIDE-HYDRAZONES, UREA DERIVATIVES, DRUG DISCOVERY, TUBERCULOSIS, INHIBITORS, DOCKING, INHA, SIMULATION, GENERATION
  • Erciyes Üniversitesi Adresli: Evet

Özet

The emergence of drug-resistant Mycobacterium tuberculosis strains has posed a driving demand in the search for more effective treatment regimens for tuberculosis. In the present study, a series of novel thiourea derivatives containing aminoguanidine moiety were synthesized by the reaction of aminoguanidine and various isothiocyanates in an attempt to discern new potent active agents against tuberculosis. The structure of synthesized compounds was characterized by FTIR,H- 1-NMR, C-13-NMR and HRMS. The proposed structure of compound BI19 was resolved using single X-ray crystallography. The compounds were tested in vitro against M. tuberculosis H37Rv for antitubercular activity. Some of them have high antimycobacterial action, for instance, BI-17 with a MIC value of 0.78 mu M and low cytotoxicity. Furthermore, computational studies and enzyme inhibition experiments were performed to identify the target for the observed antitubercular effects. (c) 2022 Elsevier B.V. All rights reserved.