Next Article in Journal
Antioxidative, Antiproliferative and Antimicrobial Activities of Phenolic Compounds from Three Myrcia Species
Next Article in Special Issue
Synthesis and Fungicidal Activity of Lansiumamide A and B and Their Derivatives
Previous Article in Journal
Quantitative Analysis of Four Catechins from Green Tea Extract in Human Plasma Using Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry for Pharmacokinetic Studies
Previous Article in Special Issue
Discovery of Novel Enhancers of Isoniazid Toxicity in Mycobacterium tuberculosis
Article Menu
Issue 4 (April) cover image

Export Article

Open AccessArticle
Molecules 2018, 23(4), 985;

Synthesis and Tuberculostatic Activity Evaluation of Novel Benzazoles with Alkyl, Cycloalkyl or Pyridine Moiety

Department of Organic Chemistry, Medical University of Gdańsk, 107 Gen. Hallera Ave., 80-416 Gdańsk, Poland
Department of Microbiology, Institute of Tuberculosis and Pulmonary Diseases, 26 Płocka Str., 01-138 Warsaw, Poland
Institute of General and Ecological Chemistry, Technical University of Łodź, Żeromskiego 116 Str., 90-924 Łódź, Poland
Author to whom correspondence should be addressed.
Received: 28 March 2018 / Revised: 18 April 2018 / Accepted: 20 April 2018 / Published: 23 April 2018
Full-Text   |   PDF [1617 KB, uploaded 3 May 2018]   |  


Compounds possessing benzimidazole system exhibit significant antituberculous activity. In order to examine how structure modifications affect tuberculostatic activity, a series of benzazole derivatives were synthesized and screened for their antitubercular activity. The compounds 120 were obtained by the reaction between o-diamine, o-aminophenol, or o-aminothiophenol with carboxylic acids or thioamides. The newly synthesized compounds were characterized by IR, 1H-NMR, 13C-NMR spectra, and elemental analysis. Synthesized benzazoles were evaluated for their tuberculostatic activity toward Mycobacterium tuberculosis strains. Quantum chemical calculations were performed to study the molecular geometry and the electronic structure of benzimidazoles GK-151B, 4, 6, and benzoxazole 11, using the Gaussian 03W software (Gaussian, Inc., Wallingford, CT, USA). Three-dimensional structure of benzimidazoles 13, MC-9, and GK-151B was determined by ab initio calculation using Gamess-US software. The activity of the received benzimidazoles was moderate or good. All of the benzoxazoles and benzothiazoles demonstrated much lower activity. Benzoxazoles were less active by about 50 times, and benzothiazole by 100 times than the benzimidazole analogs. Quantum chemical calculations showed differences in the distribution of electrostatic potential in the benzazole system of benzimidazoles and benzoxazoles. Three-dimensional structure calculations revealed how the parity of the alkyl substituent at the C2 position impacts the activity. Benzimidazole system is essential for the antituberculosis activity that is associated with the presence of the imine nitrogen atom in N-1 position. Its replacement by an oxygen or sulfur atom results in a decrease of the activity. The parity of the alkyl substituent at the C-2 position also modifies the activity. View Full-Text
Keywords: benzazole; pyridine; synthesis; tuberculostatic activity; SAR-study; quantum chemical calculations benzazole; pyridine; synthesis; tuberculostatic activity; SAR-study; quantum chemical calculations

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Krause, M.; Foks, H.; Augustynowicz-Kopeć, E.; Napiórkowska, A.; Szczesio, M.; Gobis, K. Synthesis and Tuberculostatic Activity Evaluation of Novel Benzazoles with Alkyl, Cycloalkyl or Pyridine Moiety. Molecules 2018, 23, 985.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top