Table of Contents

Abstract: By studying the literature about tetracyclines (TCs), it becomes clearly evident that TCs are very dynamic molecules. In some cases, their structure-activity-relationship (SAR) are well known, especially against bacteria, while against other targets, they are virtually unknown. In other diverse fields of research—such as neurology, oncology and virology—the utility and activity of the tetracyclines are being discovered and are also emerging as new technological fronts. The first aim of this paper is to classify the compounds already used in therapy and prepare the schematic structure that includes the next generation of TCs. The second aim of this work is to introduce a new framework for the classification of old and new TCs, using a medicinal chemistry approach to the structure of those drugs. A fully documented Structure-Activity-Relationship (SAR) is presented with the analysis data of antibacterial and nonantibacterial (antifungal, antiviral and anticancer) tetracyclines. The lipophilicity and the conformational interchangeability of the functional groups are employed to develop the rules for TC biological activity.

Abstract: The miracle of antibiotics is hard to exaggerate. Each day, in every corner of the world, antibiotics improve, or could be improving outcomes in the septic neonate, the child with pneumonia, the new mother after a complicated delivery, the patient undergoing surgery, the nursing home resident with a urinary tract infection, the patient being treated of cancer, or the trauma patient on life support. The miracle also keeps our animals healthy for effective food production. But the miracle of these ‘wonder drugs’ is under threat and may be short lived: antimicrobial resistance is relentlessly increasing, especially for Gram negative organisms, prompting the oft expressed concern that we are plummeting head-long back into the pre-antibiotics era where clinicians and families once again will have to stand by and watch patients and loved ones die from once easily-treated infections. [...]

Abstract: It was shown that 5-chloro-8-hydroxyquinoline, an antituberculosis agent, gels aqueous alcohol solutions efficiently. Thermal stability and gel-to-sol transition temperature of 1% gel in CD₃OD/D₂O (2:1) was studied by ¹H-NMR. Fibrous structures of four xerogels have been characterized by scanning electron microscope.

Abstract: The synthesis of N-heterocyclic carbene (NHC) silver(I) acetate complexes with varying lipophilic benzyl-substituents at the 1 and 3 positions starting from 4,5-diphenylimidazole, opened a new class of antibiotic drug candidates. These NHC-silver(I) acetate derivatives exhibit interesting structural motifs in the solid state and proved to be soluble and stable in biological media. The leading candidate, SBC3, which was known to exhibit good antibacterial activity in preliminary Kirby-Bauer tests, was tested quantitatively using minimum inhibitory concentrations. NHC-silver(I) acetate complexes were found to have MIC values ranging from 20 to 3.13 μg/mL for a variety of Gram-positive, Gram-negative and mycobacteria tested. These values represent good antibiotic activities against potential pathogens when compared to clinically approved antibiotics. Most striking is the fact that SBC3 is active against methicillin-resistant Staphylococcus aureus with a MIC value of 12.5 μg/mL.

Abstract: Helicobacter cinaedi causes infections, such as bacteremia, diarrhea and cellulitis in mainly immunocompromised patients. This pathogen is often problematic to analyze, and insufficient information is available, because it grows slowly and poorly in subculture under a microaerobic atmosphere. The first-choice therapy to eradicate H. cinaedi is antimicrobial chemotherapy; however, its use is linked to the development of resistance. Although we need to understand the antimicrobial resistance mechanisms of H. cinaedi, unfortunately, sufficient genetic tools for H. cinaedi have not yet been developed. In July 2012, the complete sequence of H. cinaedi strain PAGU 611, isolated from a case of human bacteremia, was announced. This strain possesses multidrug efflux systems, intrinsic antimicrobial resistance mechanisms and typical mutations in gyrA and the 23S rRNA gene, which are involved in acquired resistance to fluoroquinolones and macrolides, respectively. Here, we compare the organization and properties of the efflux systems of H. cinaedi with the multidrug efflux systems identified in other bacteria.