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

Abstract

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.

Graphical Abstract

Keywords:

• Antituberculosis activity
• antimycobacterium
• Mycobacterium tuberculosis
• N
• N-disubstituted-N′-acylthioureas

Disclosure statement

The authors report there are no competing interests to declare.

Additional information

Funding

This work was supported by Burdur Mehmet Akif Ersoy University Research Fund (BAP-Project No: 282NAP16 and BAP-Project No:0315NAP16).