The synthesis of 3,5-dibromo-2-chlorobenzoic acid hydrazides as potential antituberculous drugs
DOI:
https://doi.org/10.24959/nphj.17.2160Keywords:
hydrazides, ortho-chlorobenzoic acid, pharmacological screening, antitubercular activityAbstract
Antitubercular drugs are used for a number of decades. In each country where research is conducted strains of mycobacteria that are resistant to one or more drugs have been registered, and it causes tuberculosis with multi-drug resistance (MDR-TB). These strains of M. tuberculosis at least are not sensitive to isoniazid and rifampicin – two most powerful first-line antitubercular drugs. MDR-TB can be treated and cured using the second choice drugs. However, these treatment options are limited and require extensive chemotherapy (the treatment duration is up to two years) with drugs which are of high cost and toxicity. In some cases, a more dangerous drug resistance may develop. Tuberculosis with extensive drug resistance (EDR-TB) is more severe form of MDR-TB caused by bacteria that do not respond to the most effective antitubercular drugs of the second choice with which there are often no any further treatment options for patients. Therefore, the search and development of drugs with the antitubercular activity are important today.
Aim. To synthesize and study dibromo-substituted derivatives of ortho-chlorobenzoic acids as potential substances with the antitubercular action.
Materials and methods. Hydrazides of 3,5-dibromo-2-chlorobenzoic acid were obtained by two methods – by hydrazinolysis of acid chlorides of the corresponding acids (method 1) and by interaction of 3,5-dibromo-2-chlorobenzoic acid with hydrazines in the presence of carbonyldiimidazole (method 2).
Results and discussion. It has been found that the synthesis of hydrazides by method 2 allows obtaining the target compounds with a high yield.
Conclusions. According to the literature data the compounds synthesized are promising for the pharmacological screening on the antitubercular activity.
References
1. U. S. Agency for International Development (USAID). Available at: www/ URL: http://stbcu.com.ua
2. World Health Organization. Available at: www/ URL: http://www.who.int/en/
U.S. Food and Drug Administration (FDA). U. S. Department of Health and Human Services. Available at: www/ URL: https://www.fda.gov
Mashkovskii, M. D. (2005). Lekarstvennye sredstva, 15 izd. Moscow: Novaia Volna, 1200.
Mashkovskii, M. D. (2008). Lekarstvennye sredstva. Moscow: Novaia Volna, 748.
Drogovoz, S. M. (2010). Farmakologiia–Cito. Kharkov: SIM, 87–89.
Mandewale, M. C., Thorat, B., Nivid, Y., Jadhav, R., Nagarsekar, A., Yamgar, R. (2016). Synthesis, structural studies and antituberculosis evaluation of new hydrazone derivatives of quinoline and their Zn(II) complexes. Journal of Saudi Chemical Society, 3, 234–236. doi: 10.1016/j.jscs.2016.04.003
Velezheva, V., Brennan, P., Ivanov, P., Kornienko, A., Lyubimov, S., Kazarian, K., Apt, A. (2016). Synthesis and antituberculosis activity of indole–pyridine derived hydrazides, hydrazide–hydrazones, and thiosemicarbazones. Bioorganic & Medicinal Chemistry Letters, 26 (3), 978–985. doi: 10.1016/j.bmcl.2015.12.049
Kamat, V., Kokare, D., Naik, K., Kotian, A., Naveen, S., Dixit, S. R., Revankar, V. K. (2017). Transition metal complexes of 2–(2–(1H–benzo[d]imidazol–2–yl)hydrazono)propan–1–ol: Synthesis, characterization, crystal structures and anti–tuberculosis assay with docking studies. Polyhedron, 127, 225–237. doi: 10.1016/j.poly.2017.02.010
Ng, P. S., Manjunatha, U. H., Rao, S. P. S., Camacho, L. R., Ma, N. L., Herve, M., Kondreddi, R. R. (2015). Structure activity relationships of 4–hydroxy–2–pyridones: A novel class of antituberculosis agents. European Journal of Medicinal Chemistry, 106, 144–156. doi: 10.1016/j.ejmech.2015.10.008
Downloads
Published
Issue
Section
License
Copyright (c) 2017 National University of Pharmacy
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
