The synthesis of 3,5-dibromo-2-chlorobenzoic acid hydrazides as potential antituberculous drugs
Keywords:hydrazides, ortho-chlorobenzoic acid, pharmacological screening, antitubercular activity
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.
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