Antimicrobial Activity of Pyrazinamide Coordination Frameworks Synthesized by Mechanochemistry

Abstract

The urge for the development of a more efficient antibiotic crystalline forms led us to the disclosure of new antibiotic coordination frameworks of pyrazinamide, a well-known drug used for the treatment of tuberculosis, with some of the novel compounds unravelling improved antimycobacterial activity. Mechanochemistry was the preferred synthetic technique to yield novel compounds, allowing the reproduction of a 1D zinc framework, the synthesis of a novel hydrogen bonding manganese framework, and three new compounds with silver. The structural characterization of the novel forms is presented along with stability studies. The increased antimicrobial activity of the new silver-based frameworks against Escherichia coli, Staphylococcus aureus, and Mycobacterium smegmatis is particularly relevant.

Sustainable Mechanosynthesis of Biologically Active Molecules

“…[85] Quaresma et al also explored the formation of metal complexes based on pyrazinamide, an antimycobacterial agent, with zinc, manganese and silver nitrates exhibiting for some 1D coordination frameworks (Scheme 33). [86] Antimicrobial activity of complexes derived from manganese and silver was found to be higher than the one of pyrazinamide. Of note, the silver complex tested resulted from a stoichiometric reaction between silver(I) nitrate and pyrazinamide and its structure could not be properly identified.…”

The unique opportunities of mechanosynthesis in green and scalable fabrication of metal–organic frameworks

“…152 There are several reports on mechanochemical preparation of drug-containing metal-organic compounds. [151][152][153][154][155][156][157][158][159][160] Friščić and co-workers demonstrated that LAG methods in which water was used as grinding liquid were highly effective for the rapid and room temperature synthesis of various APIs (such as S and RS form of ibuprofen, salicylic acid or naproxen) from MgO which was previously considered an inert precursor for mechanochemical synthesis. 155,161 André group developed an effective mechanosynthesis route to construct a series of nalidixic acid-containing metal complexes and coordination polymers to overcome the low solubility of this widely used antibiotic.…”

Mechanochemistry in Portugal—A Step towards Sustainable Chemical Synthesis

“…With pyrazinamide, an antibiotic used in the treatment of tuberculosis, NG led to the formation of four complexes with Zn(II), Mn(II), and Ag(I) [ 84 ]. By adjusting the stoichiometry of the starting materials, it was possible to obtain two different Ag(I) compounds.…”