Synthesis and Antiproliferative Evaluation of 2-Deoxy-N-glycosylbenzotriazoles/imidazoles.

A series of 2-deoxy-2-iodo-α-d-mannopyranosylbenzotriazoles was synthesized using the benzyl, 4,6-benzylidene and acetyl protected D-glucal in the presence of N-iodosuccinimide (NIS). Subsequent removal of the iodine at the C-2 position using tributyltin hydride under free radical conditions afforded the 2-deoxy-α-d-glucopyranosylbenzotriazoles in moderate to high yields. This method was extended to the preparation of substituted 2-deoxy-ß-d-glucopyranosylimidazoles as well. The stereoselectivity of the addition reaction and the effect of the protecting group and temperature on anomer distribution of the benzotriazole series were also investigated. The anticancer properties of the newly synthesized compounds were evaluated in a series of viability studies using HeLa (human cervical adenocarcinoma), human breast and lung cancer cell lines. The N-[3,4,6-tri-O-benzyl-2-deoxy-α-d-glucopyranosyl]-1H-benzotriazole and the N-[3,4,6-tri-O-acetyl-2-deoxy-α-d-glucopyranosyl]-2H-benzotriazole were found to be the most potent cancer cell inhibitors at 20 µM concentrations across all four cell lines.

Selective Nonoperative and Delayed Management of Severe Asymptomatic Carotid Artery Stenosis.

OBJECTIVES: Although intervention is generally the standard of care for severe (80-99%) asymptomatic carotid stenosis, conservative management may be appropriate for a subset of patients. Our goal was to assess reasons for and outcomes of nonoperative/delayed operative management of asymptomatic severe carotid stenosis. METHODS: Institutional vascular laboratory data from 2010 to 2018 was queried for all patients who underwent a carotid duplex ultrasonography. Patients with severe asymptomatic carotid stenosis (80-99%) were included. Such stenosis was defined by an end diastolic velocity >140 cm/sec on duplex ultrasound in patients without transient ischemic attacks (TIA)/strokes ≤6 months prior to imaging. Nonoperative/delayed operative management was defined as not undergone carotid endarterectomy (CEA) or carotid artery stent (CAS) ≤6 months after imaging. Reasons for nonoperative management or delayed intervention as well as subsequent TIA/stroke and survival were determined. Kaplan-Meier analysis was performed to evaluate survival. RESULTS: Among 211 patients with severe carotid stenosis, 35 (16.6%) were managed nonoperatively or with delayed operation. Mean age in this subset was 72.6 ± 11.4 years and the majority were female (57.1%), had a smoking history (74.3%), and were on statins (91.4%) at the time of index duplex ultrasound. Reasons for no/delayed intervention were classified as severe medical comorbidities (37.1%), advanced age (17.1%), no referral for intervention (14.3%), patient refusal (14.3%), other severe concomitant cerebrovascular disease (11.4%), and active/advanced cancer (5.7%). Over a median follow-up of 35.2 months, no patients experienced TIAs/strokes attributable to carotid stenosis. One patient had a multifocal bilateral stroke after a cardiac arrest and prolonged resuscitation. A subset of patients underwent delayed CEA (8.6%) or CAS (2.9%). Four-year survival after initial imaging was 79%. CONCLUSIONS: Reasons for nonoperative and delayed operative management in our cohort of asymptomatic carotid stenosis were commonly due to comorbidities and advanced age. However, a subset of patients was never referred to vascular surgeons/interventionalists. Adverse neurologic events due to carotid stenosis were not observed during follow-up and patients had relatively high long-term survival.

Catalytic Activity, Stability, and Loading Trends of Alcohol Dehydrogenase Enzyme Encapsulated in a Metal-Organic Framework.

Recently, it has been shown that enzyme encapsulation inside metal-organic frameworks (MOFs) can increase enzyme activity and serve as protection from adverse environmental conditions. Little is understood about how the enzymes move into and are held inside the MOFs although it is believed that intermolecular forces between the MOF and the enzyme cause it to be held in place. If this process can be better understood, it can have dramatic implications on the cost-effectiveness and implementation of enzyme-MOF complexes. This is of specific importance in the medical sector for protein therapy and the industrial sector where enzyme use is expected to increase. Herein, we synthesized alcohol dehydrogenase (ADH) and PCN-333 to study encapsulation, stability, and enzyme activity to expand the knowledge of our field and offer a potential improvement to a synthetic route for biofuel synthesis. From this, we found a correlation between the concentration of a buffer and the loading of an enzyme, with surprising loading trends. We conclude that the buffer solution decreases interactions between the enzyme and MOF, supporting conventional theory and allowing it to penetrate deeper into the structure causing higher enzyme loading while allowing for excellent stability over time at various pH values and temperatures and after multiple reactions. We also observe new trends such as a rebounding effect in loading and "out-of-bounds" reactions.