Synthesis and Anti-mycobacterial evaluation of coumarin derivatives
2 Oswaldo Cruz Foundation, Aggeu Magalhães Research Center, Recife, PE, Brazil.
3 Postgraduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, Campus I, João Pessoa, PB, Brazil.
* Author to whom correspondence should be addressed.
Tuberculosis is one of the oldest known diseases of the world, remaining, within today, with the higher mortality rates caused by a single infectious agent, mainly represented by Mycobacterium tuberculosis. It's considered a greater public health problem, for reaching millions of people around the world, mainly in the developing countries, also highlighting their co-infection cases in immunocompromised patients, the example of HIV positive. Their high incidence rates are related to the non-adhesion to, and abandonment of, available treatment, due to its prolonged administration time, which allowed the appearance and increase of resistant strains causing tuberculosis. This evidences the need for the discovery and development of new drugs more efficient and powerful against pathogenic species of Mycobacterium genus. Classes of natural products, such as coumarins, have shown themselves to be powerful antimycobacteria agents in their evaluation against Mycobacterium strains. Thus, this work shows the synthesis, from protocols of O-Alkylation, O-Acetylation and Nitration well described in the literature, of coumarin derivatives, in good to greater yields, in most cases. This semi-synthetic derivatives, together with some commercial coumarins were evaluated according their antimycobacterial activities against M. tuberculosis H37Rv strains, where all demonstrated actives against the tested strains, inhibiting the growth of M. tuberculosis after eight weeks of observation, being more active than standard-drug used, Isoniazid, which non-inhibiting the growth of pathogens after the fourth week. Showing themselves as therapeutic alternatives in the development of new antimycobacterial active compounds.