Novel thiourea derivatives against Mycobacterium tuberculosis: synthesis, characterization and molecular docking studies

Kutlu E., Emen F. M., YILDIRIM K., Ataş C., Demirdogen R. E., Yesilkaynak T., ...Daha Fazla

Phosphorus, Sulfur and Silicon and the Related Elements, cilt.198, sa.10, ss.844-853, 2023 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 198 Sayı: 10
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1080/10426507.2023.2201503
  • Dergi Adı: Phosphorus, Sulfur and Silicon and the Related Elements
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core
  • Sayfa Sayıları: ss.844-853
  • Anahtar Kelimeler: Antituberculosis activity, antimycobacterium, Mycobacterium tuberculosis, N, N-disubstituted-N'~-acylthioureas
  • Akdeniz Üniversitesi Adresli: Evet

Özet

N-((2-chloropyridin-3-yl)carbamothioyl)thiophene-2-carboxamide (HL1), N-((6-methylpyridin-2-yl)carbamothioyl)thiophene-2-carboxamide (HL2), N-(allylcarbamothioyl)thiophene-2-carboxamide (HL3), 2-chloro-N-(methyl(1-phenylethyl)carbamothioyl)benzamide (HL4) and 2-chloro-N-(bis((R)-1-phenylethyl)carbamothioyl)benzamide (HL5) were synthesized and characterized via FT-IR, 1H-NMR, 13C-NMR and HR-MS techniques and HL3 was characterized via a single crystal X-ray diffraction experiment. The antituberculosis activity of the synthesized thiourea derivatives was tested against the H37RV (ATCC27294), ATCC35822 (INH resistant), ATCC35838 (RIF resistant), ATCC35820 (STM resistant) and ATCC35837 (EMB resistant) standard bacteria strains. The thiourea derivatives were tested on two MDR and one primary drug-sensitive isolates with the microplate nitrate reductase test method. The results indicated that HL2 and HL3 had tuberculosis activity on some of the isolates. It was observed that HL4 was the most effective among all the thiourea derivatives. The interaction mechanism of the synthesized compounds on 2X23, a tuberculosis protein, was investigated via molecular docking method. The interaction was observed to occur over S and Cl atoms in all the compounds. The compounds containing the methyl group were observed to interact via this group.