A new series of phenylthiazoles with t-butyl lipophilic component was synthesized and their antibacterial activity against a panel of multidrug-resistant bacterial pathogens was evaluated. Five compounds demonstrated promising antibacterial activity against methicillin-resistant staphylococcal strains and several vancomycin-resistant staphylococcal and enterococcal species. Additionally, three derivatives 19, 23 and 26 exhibited rapid bactericidal activity, and remarkable ability to disrupt mature biofilm produced by MRSA USA300. More importantly, a resistant mutant to 19 couldn't be isolated after subjecting MRSA to sub-lethal doses for 14 days. Lastly, this new series of phenylthiazoles possesses an advantageous attribute over the first-generation compounds in their stability to hepatic metabolism, with a biological half-life of more than 9 h.

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Fully integrated wearable sensors are capable of dynamically, directly, and independently tracking biomarkers in raw noninvasive biofluids without any other equipment or accessories by integrating the unique on-body monitoring feature with the special complete functional implementation attribute. Sweat, saliva, and urine are three important noninvasive biofluids, and changes in their biomarkers hold great potential for revealing physiological conditions. However, it is still a challenge to design single fully integrated wearable sensor arrays (FIWSAs) that are universally able to concurrently measure electrolytes and metabolites in three of the most common noninvasive biofluids including sweat, saliva, and urine. Here, we propose the first single universal FIWSAs for wirelessly, noninvasively, and simultaneously measuring various metabolites (i.e., uric acid) and electrolytes (i.e., Na + and H + ) in raw sweat, saliva, or urine under subjects' exercise by integrating the specifically designed microfluidic, sensing, and electronic modules in a seamless manner. We evaluate its utility for noninvasive gout management in healthy subjects and in gout patients through a purine-rich meal challenge and with a medicine-treatment control, respectively. Noninvasive monitoring of multiple electrolytes and metabolites in a variety of raw noninvasive biofluids via such single universal FIWSAs may enrich the understanding of the biomarkers' levels in the body and would also facilitate self-health management.

Bacterial resistance to antibiotics is presently one of the most pressing healthcare challenges and necessitates the discovery of new antibacterials with unique chemical scaffolds. However, the determination of the optimal balance between structural requirements for pharmacological action and pharmacokinetic properties of novel antibacterial compounds is a significant challenge in drug development. The incorporation of lipophilic moieties within a compound’s core structure can enhance biological activity but have a deleterious effect on drug-like properties. In this Article, the lipophilicity of alkynylphenylthiazoles, previously identified as novel antibacterial agents, was reduced by introducing cyclic amines to the lipophilic side chain. In this regard, substitution with methylpiperidine (compounds 14–16) and thiomorpholine (compound 19) substituents significantly enhanced the aqueous solubility profile of the new compounds more than 150-fold compared to the first-generation lead compound 1b. Consequently, the pharmacokinetic profile of compound 15 was significantly enhanced with a notable improvement in both half-life and the time the compound’s plasma concentration remained above its minimum inhibitory concentration (MIC) against methicillin-resistant Staphylococcus aureus (MRSA). In addition, compounds 14–16 and 19 were found to exert a bactericidal mode of action against MRSA and were not susceptible to resistance formation after 14 serial passages. Moreover, these compounds (at 2× MIC) were superior to the antibiotic vancomycin in the disruption of the mature MRSA biofilm. The modifications to the alkynylphenylthiazoles reported herein successfully improved the pharmacokinetic profile of this new series while maintaining the compounds’ biological activity against MRSA.

The structure-activity and structure-kinetic relationships of a new tert-butylphenylthiazole series with oxadiazole linkers were conducted with the objective of obtaining a new orally available antibacterial compounds. Twenty-two new compounds were prepared, purified and identified. Their activity against methicillin-resistant Staphylococcus aureus were examined. Compound 20 with 3-hydroxyazetidine as a nitrogenous side chain showed promising activity against twenty-four clinical isolates, including vancomycin-resistant staphylococcal and enterococcal species with MIC values ranging from 4-8 mg mL À1 . Additional advantages of this compound include an ability to eradicate staphylococcal biofilm mass in a dose-dependent manner as well as high metabolic stability after an oral dose of 25 mg kg À1 with a biological half-life that exceeds 5 hours and a plasma concentration (C max ) that exceeds the MIC values.

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Antifungals are effective antimicrobial agents broadly used in medical practice. Severe acute liver failure from oral or IV administration of antifungals is a rare but long-standing clinical challenge. We aimed to approximate the risk of clinical acute liver injury among users of oral antifungals in the general population. This review was completed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Six articles were included, comprising case reports and cohort studies, after eliminating duplicate publications. No randomized control studies were found. In all studies, the duration of antifungal use was associated with significantly increased liver enzyme levels. Although it is not very common for patients on antifungals to develop acute liver failure, the prognosis is often good with swift discontinuation of the drug and proper treatment. Liver function evaluation before treatment and periodic monitoring every three to six weeks after commencement of treatment is suggested.

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