ABSTRACT
A feasible protocol that uses atomic groups (KSCN, KSeCN, and NH2CN), o-bromobenzoyl hydrazides, and formyls as reaction factors to synthesize N-fused 1,2,4-triazole with benzothiazides, benzoselenazinones, and quinazolinones was proposed. The method overcomes the lengthy multistep synthesis, narrow substrate scope, and toxicity challenge induced by the use or production of hazardous substances. It also enables the development of fused-heterocyclic selenium and quinazolinone derivatives. Their fluorescent performance further demonstrates the practicability of this methodology.
ABSTRACT
Drug-induced liver injury (DILI) is a persistent concern in drug discovery and clinical medicine. The current clinical methods to assay DILI by analyzing the enzymes in serum are still not optimal. Recent studies showed that fluorescent sensors would be efficient tools for detecting the concentration and distribution of DILI indicators with high sensitivity and specificity, in real-time, in situ, and with low damage to biosamples, as well as diagnosing DILI. This review focuses on the assessment of DILI, introduces the current mechanisms of DILI, and summarizes the design strategies of fluorescent sensors for DILI indicators, including ions, small molecules, and related enzymes. Some challenges for developing DILI diagnostic fluorescent sensors are put forward. We believe that these design strategies and challenges to evaluate DILI will inspire chemists and give them opportunities to further develop other fluorescent sensors for accurate diagnoses and therapies for other diseases.
Subject(s)
Chemical and Drug Induced Liver Injury , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/etiology , HumansABSTRACT
Drug-induced hepatotoxicity is the main cause of acute liver injury, and its early diagnosis is indispensable in pharmacological and pathological studies. As a hepatotoxicity indicator, the GSH distribution in the liver could reflect the damage degree in situ. In this work, we have provided a theoretical design strategy to determine the generation of photo-induced electron transfer mechanism and achieve high selectivity for the target. After that, we precisely synthesized a novel near-infrared fluorescent probe BSR1 to specifically monitor endogenous GSH and hepatotoxicity in biosystem with a moderate fluorescent quantum yield (Φ = 0.394) and low detection limit (83 nM) under this strategy. Moreover, this mapping method for imaging GSH depletion in vivo to assay hepatotoxicity may provide a powerful molecular tool for early diagnosis of some diseases and contribute to assay hepatotoxicity for the development of new drugs. Importantly, this theoretical calculation-guided design strategy may provide an effective way for the precise synthesis of the target-specific fluorescent probe and change this research area from "trial-and-error" to concrete molecular engineering.
Subject(s)
Chemical and Drug Induced Liver Injury/pathology , Fluorescent Dyes/chemical synthesis , Glutathione/analysis , Liver/pathology , Models, Theoretical , Animals , Cell Line , Disease Models, Animal , Fluorescent Dyes/chemistry , Humans , Mice , Optical Phenomena , Spectrometry, FluorescenceABSTRACT
OBJECTIVE: To study the indication and contraindication of opening pulp chamber therapy for patients with a history of remote myocardial infarction. METHODS: Blood pressure (BP), heart beat rate and electrocardiographic examination were determined during opening pulp chamber therapy in patients with acute and chronic pulpititis and a history of remote myocardial infarction. RESULTS: High blood pressure and quick heart beat were found during local anaesthetic injection and opening of pulp chamber (during local anaesthetic injection BP increased by 12.52/8.04 mmHg, heart rate by 4.02 times/min;during opening of pulp chamber BP and heart rate increased by 15.43/8.0 mmHg, 6.37 times/min respectively). Electrocardiogram showed myocardial ischemic pattern deteriorated in some patients with the history of coronary insufficiency. CONCLUSIONS: Most patients can bear it. Comprehensive physical examinations, evaluations of the patients' cardial status, mental state and indispensible equipment are necessary. The therapy is recommended to be operated under the monitor electrocardiography for the safety of the patients.
