Novel isatin conjugates endowed with analgesic and anti-inflammatory properties: design, synthesis and biological evaluation.

Aims: This study aimed to develop novel molecular hybrid conjugates integrating isatin, rhodanine, and phthalimide pharmacophores to create effective analgesic and anti-inflammatory agents with improved safety profiles over existing treatments.

Materials & Methods: A series of hybrid conjugates () were synthesized and evaluated through in vitro and in vivo biological assays. The most promising compound, , underwent extensive pharmacological and toxicological evaluations.

Cerebral Embolic Protection by Geographic Region: A Post Hoc Analysis of the PROTECTED TAVR Randomized Clinical Trial.

Importance: Transcatheter aortic valve replacement (TAVR) is an established treatment option for many patients with severe symptomatic aortic stenosis; however, debris dislodged during the procedure can cause embolic stroke. The Sentinel cerebral embolic protection (CEP) device is approved for capture and removal of embolic material during TAVR but its efficacy has been debated.

Objective: To explore regional differences in the association of CEP utilization with stroke outcomes in patients undergoing TAVR.

Rhodium-Catalyzed Functionalization and Annulation of N-Aryl Phthalazinediones with Allyl Alcohols.

A direct ortho-Csp-H acylalkylation of 2-aryl-2,3-dihydrophthalazine-1,4-diones with unsubstituted and substituted allyl alcohols is achieved in high yields through Rh(III)-catalyzed C-H bond activation process. The additional employment of Cu(OAc)⋅2HO as an oxidant detour the reaction towards [4+1] annulation, producing 13-(2-oxopropyl)-13H-indazolo[1,2-b]phthalazine-6,11-diones in moderate yields. Interestingly, Lawesson's reagent-mediated conditions accomplished intramolecular cyclization in ortho-(formylalkylated)-2,3-dihydrophthalazine-1,4-diones to produce diazepino[1,2-b]phthalazine-diones in moderate yields.

Outcomes of Transcatheter Aortic Valve Replacement Using Third-Generation Balloon-Expandable Versus Self-Expanding Valves: A Meta-analysis.

Background: The choice of transcatheter aortic valve replacement (TAVR) prosthesis is crucial in optimizing short- and long-term outcomes. The objective of this study was to conduct a meta-analysis comparing outcomes of third-generation balloon-expandable valves (BEV) vs self-expanding valves (SEV).

Methods: Electronic databases were searched from inception to June 2023 for studies comparing third-generation BEV vs SEV.

Iridium-catalyzed diacylmethylation of tyrosine and its peptides with sulfoxonium ylides.

Pyridyloxy-directed Ir(III)-catalyzed diacylmethylation of protected tyrosines was achieved with alkyl and (hetero)aryl sulfoxonium ylides, furnishing tyrosine-based unnatural amino acids in good yields. Furthermore, the late stage exemplification of the strategy was successfully accomplished in tyrosine-containing dipeptides, tripeptides and tetrapeptides in moderate yields. This methodology is distinguished by its site-selectivity, tolerance of sensitive functional groups, scalability, and retention of the chiral configuration for tyrosine motifs.

Lead Extraction and Baffle Stenting in a Patient with Transposition of the Great Arteries.

This case report discusses a 42-year-old male with dextro-transposition of the great arteries (D-TGA) status post Mustard repair and sick sinus syndrome status post dual-chamber pacemaker implant, who developed symptomatic superior vena cava (SVC) baffle stenosis. He was treated with a combined pacemaker extraction and subsequent SVC baffle stenting. The case highlights the complexities of treating SVC baffle stenosis in the presence of cardiac implantable devices and demonstrates the efficacy of this combined approach.

Rhodium-Catalyzed Regioselective C3 Functionalization of Tyrosines with Maleimides and Its Late-Stage Peptide Exemplification.

Pyridyloxy-directed Rh(III)-catalyzed regioselective C3-H alkenylation of protected tyrosines was achieved with -aryl and -alkyl maleimides, furnishing a series of maleimide-appended tyrosine-based unnatural amino acids in good yields. Further, the late-stage exemplification of the strategy was successfully accomplished on tyrosine-containing dipeptides, tripeptides, and tetrapeptides in moderate reactivity. Also, the chemical applications of the strategy were successfully executed toward nailing tyrosine with other amino acids via a maleimide linker and intramolecular hydroarylation to produce tyrosine-centered stapled products and succinimide-glued macrocyclized products, respectively.

Synthesis of modified bile acids palladium-catalyzed C(sp)-H (hetero)arylation.

A Pd(II)-catalyzed strategy for the diastereo- and regioselective (hetero)arylation of unactivated C(sp)-H bonds in bile acids is accomplished with aryl and heteroaryl iodides under solvent-free conditions using the 8-aminoquinoline auxiliary as a directing group. This methodology demonstrated excellent functional group tolerance with respect to aryl/heteroaryl iodides on -protected -(quinolin-8-yl)cholyl/deoxycholyl amides to afford β-C(sp)-H (hetero)arylated products in good-to-excellent yields. Moreover, the 8-aminoquinoline (AQ) auxiliary can easily be removed to obtain modified bile acids.

Steroid-triazole conjugates: A brief overview of synthesis and their application as anticancer agents.

Steroids are biomolecules that play pivotal roles in various physiological and drug discovery processes. Abundant research has been fuelled towards steroid-heterocycles conjugates over the last few decades as potential therapeutic agents against various diseases especially as anticancer agents. In this context various steroid-triazole conjugates have been synthesized and studied for their anticancer potential against various cancer cell lines.

Temozolomide-fatty acid conjugates for glioblastoma multiforme: In vitro and in vivo evaluation.

Glioblastoma multiforme (GBM) is the deadliest brain tumor with a poor prognosis and limited therapeutic options. Temozolomide (TMZ) is the first-line chemotherapeutic agent used for the treatment of GBM; however, it suffers from several limitations, including short half-life, rapid metabolism, <1% brain bioavailability, methyl guanine methyl transferase (MGMT) based chemoresistance, and hematological toxicities. Several approaches have been adopted to overcome these limitations, particularly by using nanotechnology-based systems, but its physicochemical properties make TMZ challenging to load into these nanocarriers.

Long-Term Follow-up of Subjects With Iliac Occlusive Disease Treated With the Viabahn VBX Balloon-Expandable Endoprosthesis.

Introduction: This physician-initiated study provides 5-year (i.e., long-term) treatment durability data from 3 top recruitment sites that participated in the prospective, multicenter, nonrandomized, single-arm VBX FLEX clinical study (ClinicalTrials.

Predictors of cardiovascular implantable electronic device dependence at long-term follow-up after alcohol septal ablation in hypertrophic cardiomyopathy patients.

Background: The most common complication of alcohol septal ablation (ASA) is transient periprocedural high-grade AV block (HGAVB). To date, no long-term follow-up of cardiovascular implantable electronic device (CIED) utilization after ASA has been reported. We hypothesized that CIED dependence on long-term follow-up can be predicted by ECG or procedural characteristics.

Tandem Transformation of Indazolones to Quinazolinones through Pd-Catalyzed Carbene Insertion into an N-N Bond.

Serendipitous and expedite transformation of 1-aryl- and 2-aryl-1,2-dihydro-3-indazol-3-ones to 1,2-di(hetero)aryl- and 2,3-di(hetero)aryl-2,3-dihydroquinazolin-4(1)-ones, respectively, was achieved in high efficiency by reacting them with aldehydic -tosylhydrazones. The protocol proceeded through a cascade process involving base-mediated Pd-carbenoid generation by the decomposition of -tosylhydrazones, nucleophilic attack of indazolone on the Pd-carbenoid complex, and intramolecular ring expansion via N-N bond cleavage. The utility of the strategy is demonstrated toward the synthesis of bioactive NPS 53574, a calcium receptor antagonist.

Rhodium-Catalyzed Annulation of Vinylated Tyrosines with Internal Alkynes to Access Oxepine-Mounted Unnatural Tyrosines and Its Peptide Late Stage Functionalization.

A Rh(III)-catalyzed [5+2] annulation of vinyl tyrosines with symmetrical and unsymmetrical internal alkynes was achieved, furnishing a series of oxepine-mounted tyrosine-based unnatural amino acids. In addition, the chemical applicability of the developed strategy was exemplified by stapling amino acid/peptide-appended alkynes with vinyl tyrosines and late stage functionalization of tyrosine-containing dipeptides and tripeptide with internal alkynes.

Patient- and Process-Related Contributors to the Underuse of Aortic Valve Replacement and Subsequent Mortality in Ambulatory Patients With Severe Aortic Stenosis.

Background Many patients with severe aortic stenosis (AS) and an indication for aortic valve replacement (AVR) do not undergo treatment. The reasons for this have not been well studied in the transcatheter AVR era. We sought to determine how patient- and process-specific factors affected AVR use in patients with severe AS.

Ruthenium-catalyzed (spiro)annulation of -aryl-2,3-dihydrophthalazine-1,4-diones with quinones to access pentacyclic spiro-indazolones and fused-cinnolines.

Ru(II)-catalyzed strategies were developed for the [4 + 1] and [4 + 2] oxidative coupling between -aryl-2,3-dihydrophthalazine-1,4-diones and 1,4-benzoquinones, achieving spiro-indazolones and fused-cinnolines, respectively. Mild, aerobic and external oxidant-free conditions, as well as the use of a ruthenium catalyst for such (spiro)annulative strategies with quinones over reported Rh/Ir-catalyts, underline the rewards of the disclosed protocols.

Development of Isatin-Based Schiff Bases Targeting VEGFR-2 Inhibition: Synthesis, Characterization, Antiproliferative Properties, and QSAR Studies.

Three sets of isatin-based Schiff bases were synthesized utilizing the molecular hybridization approach. Some of the synthesized Schiff bases show significant to moderate antiproliferative properties against MCF7 (breast), HCT116 (colon), and PaCa2 (pancreatic) cancer cell lines with potency compared to reference drugs 5-fluorouracil (5-FU) and Sunitinib. Among all, compound 17 f (3-((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)imino)-1-((1-(2-methoxyphenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methylindolin-2-one) exhibits promising antiproliferative properties against the MCF7 cancer cell line with 2.

Synthesis, Antibacterial Evaluation, and Computational Studies of a Diverse Set of Linezolid Conjugates.

The development of new antibiotics to treat multidrug-resistant (MDR) bacteria or possess broad-spectrum activity is one of the challenging tasks. Unfortunately, there are not many new antibiotics in clinical trials. So, the molecular hybridization approach could be an effective strategy to develop potential drug candidates using the known scaffolds.

Regiodivergent Synthesis of Cinnoline-Fused Indazolones through Pd-Catalyzed Annulation of 1-Arylindazolones with Allenoates.

A tender-hearted Pd(II)-catalyzed C-H activation of 1-arylindazolones followed by an oxidative [4 + 2] annulation reaction has been accomplished, engaging allenoates as annulating partners. Using this strategy, two different regioisomeric forms of cinnoline-fused indazolones possessing internal and exocyclic double bonds were synthesized in acetic acid and dioxane, respectively. Mild and aerobic conditions, avoiding the use of any metal-oxidant, highlights the rewards of this oxidative annulation protocol.

Relation of Subacute Kidney Injury to Mortality After Transcatheter Aortic Valve Implantation.

Acute kidney injury after transcatheter aortic valve implantation (TAVI) has been associated with adverse outcomes; however, data are limited on the subacute changes in renal function that occur after discharge and their impact on clinical outcomes. This study investigates the relation between subacute changes in kidney function at 30 days after TAVI and survival. Patients from 2 centers who underwent TAVI and survived beyond 30 days with baseline, in-hospital, and 30-day measures of renal function were retrospectively analyzed.

Bile-Acid-Appended Triazolyl Aryl Ketones: Design, Synthesis, In Vitro Anticancer Activity and Pharmacokinetics in Rats.

A library of bile-acid-appended triazolyl aryl ketones was synthesized and characterized by detailed spectroscopic techniques such as H and C NMR, HRMS and HPLC. All the synthesized conjugates were evaluated for their cytotoxicity at 10 µM against MCF-7 (human breast adenocarcinoma) and 4T1 (mouse mammary carcinoma) cells. In vitro cytotoxicity studies on the synthesized conjugates against MCF-7 and 4T1 cells indicated one of the conjugate to be most active against both cancer cell lines, with IC values of 5.