Impact of Pericervical Dentin on Fracture Resistance of Endodontically Treated Posterior Permanent Teeth: A Systematic Review and Meta-analysis.

OBJECTIVE: The main aim of this present systematic review is to evaluate if the preservation of pericervical dentin (PCD) increases the fracture resistance of endodontically treated permanent posterior teeth. MATERIALS AND METHODS: Two independent reviewers conducted a comprehensive review of all published studies from 2007 (1/1/2007) to 2023 (31/5/23) since the concept of PCD first appeared in the literature in 2007. Searches were conducted in multiple electronic database engines: PubMed, Scopus, EBSCO (Dentistry and oral health sciences), Web of Sciences (WOS), Cochrane, Google Scholar and Open Grey, Ovid and Shodhganga, in addition to cross-references and hand search. Articles were chosen according to a certain inclusion and exclusion criteria, which, in brief, are laboratory-based studies published in English that assess the impact of PCD on fracture resistance of endodontically treated permanent posterior teeth. Using domains, such as sample size, sample dimensions, and control group as quality assessment criteria, evaluated the selected articles and classified them according to their risk of bias into low, moderate, and high. A meta-analysis was conducted using random effects modeling at a significance level of p < 0.05. RESULTS: A total of studies 6,043 were retrieved from 10 different electronic search databases and hand searches, but only 12 laboratory-based studies were selected after removing duplicates and applying the eligibility criteria. Of the included 12 studies, nine studies showed low risk of bias and three studies showed moderate risk of bias. Two studies showed related data for meta-analysis, the difference observed between the two studies is statistically non-significant. CONCLUSION: Based on the results of the study, there is evidence to support that PCD preservation offers fracture resistance to the endodontically treated posterior teeth. CLINICAL SIGNIFICANCE: The practice of conservative cavity preparation and avoiding the usage of instruments with high taper increases the fracture resistance of the tooth by retaining the PCD. How to cite this article: Haridoss S, Rajendran M, Swaminathan K, et al. Impact of Pericervical Dentin on Fracture Resistance of Endodontically Treated Posterior Permanent Teeth: A Systematic Review and Meta-analysis. J Contemp Dent Pract 2024;25(4):372-385.

Development of potent cholinesterase inhibitors based on a marine pharmacophore.

The management of neurological disorders such as dementia associated with Alzheimer's or Parkinson's disease includes the use of cholinesterase inhibitors. These compounds can slow down the progression of these diseases and can also be used in the treatment of glaucoma and myasthenia gravis. The majority of the cholinesterase inhibitors used in the clinic are derived from natural products and our current paper describes the use of a small marine pharmacophore to develop potent and selective cholinesterase inhibitors. Fourteen small inhibitors were designed based on recent discoveries about the inhibitory potential of a range of related marine secondary metabolites. The compounds were evaluated, in kinetic enzymatic assays, for their ability to inhibit three different cholinesterase enzymes and it was shown that compounds with a high inhibitory activity towards electric eel and human recombinant acetylcholinesterase (IC50 between 20-70 µM) could be prepared. It was also shown that this compound class was particularly active against horse serum butyrylcholinesterase, with IC50 values between 0.8-16 µM, which is an order of magnitude more potent than the clinically used positive control neostigmine. The compounds were further tested for off-target toxicity against both human umbilical vein endothelial cells and bovine and human erythrocytes and were shown to display a low mammalian cellular toxicity. Overall, the study illustrates how the brominated dipeptide marine pharmacophore can be used as a versatile natural scaffold for the design of potent, and selective cholinesterase inhibitors.

Synthesis of 5,7-diarylindoles via Suzuki-Miyaura coupling in water.

The synthesis of novel 5,7-diaryl and diheteroaryl indoles has been explored via efficient double Suzuki-Miyaura coupling. The method notably employs a low catalyst loading of Pd(PPh3)4 (1.5 mol%/coupling) and water as the reaction solvent to obtain 5,7-diarylated indoles without using N-protecting groups in up to 91% yield. The approach is also suitable for N-protected and 3-substituted indoles and constitutes an important green and convenient arylation strategy for the benzenoid ring of indoles. The synthesized diarylindoles are fluorescent.

Phidianidine A and Synthetic Analogues as Naturally Inspired Marine Antifoulants.

Stationary and slow-moving marine organisms regularly employ a natural product chemical defense to prevent being colonized by marine micro- and macroorganisms. While these natural antifoulants can be structurally diverse, they often display highly conserved chemistries and physicochemical properties, suggesting a natural marine antifouling pharmacophore. In our current report, we investigate the marine natural product phidianidine A, which displays several chemical properties found in highly potent marine antifoulants. Phidianidine A and synthetic analogues were screened against the settlement and metamorphosis of Amphibalanus improvisus cyprids, and several of the compounds displayed inhibitory activities at low micromolar concentrations with IC50 values down to 0.7 µg/mL observed. The settlement study highlights that phidianidine A is a potent natural antifoulant and that the scaffold can be tuned to generate simpler and improved synthetic analogues. The bioactivity is closely linked to the size of the compound and to its basicity. The study also illustrates that active analogues can be prepared in the absence of the natural constrained 1,2,4-oxadiazole ring. A synthetic lead analogue of phidianidine A was incorporated in a coating and included in antifouling field trials, where it was shown that the coating induced potent inhibition of marine bacteria and microalgae settlement.

Hit to Leads with Cytotoxic Effect in Leukemic Cells: Total Synthesis Intermediates as a Molecule Treasure Chest.

A previously designed and developed 12-step total synthesis that includes [1,1'-biphenyl]-2-amine and carbazole intermediates and that ultimately produces the carbazole alkaloid carbazomycin G was exploited as a screening compound library with the goal of identifying potential lead compound(s) with cytotoxic effect. These compounds were investigated by using in-vitro tests involving the two human cell lines HL-60 and MOLM-13, which both model acute myeloid leukaemia (AML). The in-vitro biological test results were used together with the molecular structures of the various intermediates in a concise SAR analysis. Several of the intermediates revealed cytotoxicity (IC50 <10-4  M), although the final natural product carbazomycin G did not reveal cytotoxicity versus the two said human cell lines.

A scalable and green one-minute synthesis of substituted phenols.

A mild, green and highly efficient protocol was developed for the synthesis of substituted phenols via ipso-hydroxylation of arylboronic acids in ethanol. The method utilizes the combination of aqueous hydrogen peroxide as the oxidant and H2O2/HBr as the reagent under unprecedentedly simple and convenient conditions. A wide range of arylboronic acids were smoothly transformed into substituted phenols in very good to excellent yields without chromatographic purification. The reaction is scalable up to at least 5 grams at room temperature with one-minute reaction time and can be combined in a one-pot sequence with bromination and Pd-catalyzed cross-coupling to generate more diverse, highly substituted phenols.