Furthermore, infections caused by multiresistant organisms is presently associated with extended hospitalization periods causing a severe burden to healthcare systems worldwide. This impressive death toll is estimated to reach 10 million by 2050, with a huge negative social and economic global impact. Presently, resistance to multiple antibiotics is estimated to cause a total of 700,000 deaths per year worldwide. Together with the shortage of investment in novel antibiotics, a steady worldwide increase in microbial resistance to antibiotics has been reported. In the 1980s and 1990s, many pharmaceutical companies abandoned antibiotics research and development, mainly because of the huge investment required and regulatory barriers. The discovery and use of antibiotics has revolutionized modern medicine, reaching its golden age between the 1940s and the mid-1960s with the discovery of β-lactams, aminoglycosides, tetracyclines, glycopeptides, macrolides, chloramphenicols, ansamycins, and streptogramins, which are still currently in clinical use. The nature of the anionic counterparts present on the salts was found to play a minor role in the antibacterial activity. The analogous cyclen species presents a lower activity, revealing that the size of the macrocyclic backbone is an important requirement for the antibacterial activity of the tetraazamacrocycles. The most active compounds against both bacterial strains were the trans-disubstituted cyclam salts displaying CF 3 groups in the para-position of the aromatic rings of the macrocyclic pendant arms. The results obtained show that the chemical nature, polarity, and substitution patterns of the benzyl groups, as well as the number of pendant arms, are critical parameters for the antibacterial activity of the cyclam-based salts.
The newly synthesized compounds are monosubstituted and trans-disubstituted tetraazamacrocycles that display benzyl, methylbenzyl, trifluoromethylbenzyl, or trifluoroethylbenzyl substituents appended on the nitrogen atoms of the macrocyclic ring.
WHAS THE SUPPLEMENTARY ANGLE OF 142.8 SERIES
A series of cyclam- and cyclen-derived salts are described in the present work they were designed specifically to gain insights into their structure and antibacterial activity towards Staphylococcus aureus and Escherichia coli, used respectively, as Gram-positive and Gram-negative model organisms.
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