Recent Advances in Metal-Catalyzed Approaches for the Synthesis of Quinazoline Derivatives.

Quinazolines are an important class of heterocyclic compounds that have proven their significance, especially in the field of organic synthesis and medicinal chemistry because of their wide range of biological and pharmacological properties. Thus, numerous synthetic methods have been developed for the synthesis of quinazolines and their derivatives. This review article briefly outlines the new synthetic methods for compounds containing the quinazoline scaffold employing transition metal-catalyzed reactions.

Phenyliodine(III) Diacetate-Mediated 1,2-ipso-Migration in Mannich Bases of Imidazo[1,2-a]pyridines: Preparation of N-Acetoxymethyl/Alkoxymethyl-N-arylimidazo[1,2-a]pyridine-3-amines.

Phenyliodine(III) diacetate -mediated 1,2-ipso-migration of an imidazo[1,2-a]pyridine ring via the formation of an aziridine intermediate in Mannich bases derived from imidazo[1,2-a]pyridines, 2-pyridylamines or arylamines, and formaldehyde is reported. The imidazo[1,2-a]pyridines bearing different substituents showed excellent migratory aptitude and resulted in corresponding N-acetoxymethyl-, N-alkoxymethyl-, and N-hydroxymethyl-N-arylimidazo[1,2-a]pyridine-3-amine derivatives in moderate to excellent (42 examples; 35-93%) yields. Radical trapping experiments confirmed the involvement of a non-radical intermediate. The developed protocol is amenable for a scale-up reaction, and synthetic utility of N-acetoxymethyl products was demonstrated by transforming them to corresponding N-(pyridin-2-yl)imidazo[1,2-a]pyridin-3-amines.

A straightforward TBHP-mediated synthesis of 2-amidobenzoic acids from 2-arylindoles and their antimicrobial activity.

A simple and highly efficient strategy has been developed for the synthesis of 2-amidobenzoic acids through the tert-butyl hydroperoxide (TBHP)-mediated oxygenation and sequential ring opening of 2-arylindoles in a one-pot fashion under metal-free aerobic conditions. The developed synthetic protocol is operationally simple, tolerates a wide range of functional groups, and is amenable to the gram-scale. Radical trapping experiments revealed that the reaction involves a radical pathway. The synthesized compounds (2a-s) were tested for in vitro antimicrobial activity. Among all screened compounds, 2d showed the maximum antibacterial activity against P. aerugunosa (ZOI = 17 mm, MIC = 32 µg mL-1) and compounds 2d and 2p showed the maximum (32 µg mL-1) antifungal activity against A. flavus and C. albicans.

Metal-free synthesis of aminomethylated imidazoheterocycles: dual role of tert-butyl hydroperoxide as both an oxidant and a methylene source.

A novel and efficient aminomethylation approach has been developed for the regioselective functionalization of imidazoheterocycles under metal-free conditions. A wide range of imidazoheterocycles and 2/4-aminoazaheterocycles successfully provided corresponding aminomethylated imidazoheterocycles in moderate to excellent (33-80%) yields. The isotopic labelling study suggested that TBHP played a dual role as both an oxidant and a methylene source in this transformation. The developed protocol follows a radical pathway which is supported by radical trapping experiments.

H2O2/DMSO-Promoted Regioselective Synthesis of 3,3'-Bisimidazopyridinylmethanes via Intermolecular Oxidative C(sp(2))-H Bond Activation of Imidazoheterocycles.

In the past decade, metal-free approaches for C-C bond formation have attracted a great deal of attention due to their ease of use and low cost. This report represents a novel and metal-free synthesis of 3,3'-bisimidazopyridinylmethanes via intermolecular oxidative C(sp(2))-H bond functionalization of imidazo[1,2-a]pyridines with dimethyl sulfoxide as the carbon synthon (CH2) using H2O2 as a mild oxidant under air. A library of 3,3'-bis(2-arylimidazo[1,2-a]pyridin-3-yl)methanes has been achieved in good to excellent yields. The present methodology has been successfully applied to imidazo[2,1-b]thiazoles and imidazo[2,1-b]benzothiazoles. Furthermore, the current approach was also extended for the synthesis of unsymmetrical 3,3'-bisimidazopyridinylmethanes under optimized reaction conditions. A mechanistic pathway is proposed on the basis of experiments with radical scavengers and DMSO-d6 and ESI-MS observations.

Naturally Occurring Carbazole Alkaloids from Murraya koenigii as Potential Antidiabetic Agents.

This study identified koenidine (4) as a metabolically stable antidiabetic compound, when evaluated in a rodent type 2 model (leptin receptor-deficient db/db mice), and showed a considerable reduction in the postprandial blood glucose profile with an improvement in insulin sensitivity. Biological studies were directed from the preliminary in vitro evaluation of the effects of isolated carbazole alkaloids (1-6) on glucose uptake and GLUT4 translocation in L6-GLUT4myc myotubes, followed by an investigation of their activity (2-5) in streptozotocin-induced diabetic rats. The effect of koenidine (4) on GLUT4 translocation was mediated by the AKT-dependent signaling pathway in L6-GLUT4myc myotubes. Moreover, in vivo pharmacokinetic studies of compounds 2 and 4 clearly showed that compound 4 was 2.7 times more bioavailable than compound 2, resulting in a superior in vivo efficacy. Therefore, these studies suggested that koenidine (4) may serve as a promising lead natural scaffold for managing insulin resistance and diabetes.

Substrate Controlled Synthesis of Benzisoxazole and Benzisothiazole Derivatives via PhI(OAc)2-Mediated Oxidation Followed by Intramolecular Oxidative O-N/S-N Bond Formation.

A phenyliodine(III) diacetate (PIDA)-mediated, highly efficient and tandem approach for the synthesis of aryldiazenylisoxazolo(isothiazolo)arenes from simple 2-amino-N'-arylbenzohydrazides has been developed. The reaction proceeds via formation of (E)-(2-aminoaryl)(aryldiazenyl)methanone as the key intermediate, followed by intramolecular oxidative O-N/S-N bond formation in one pot at room temperature. The quiet different reactivity of the substrate is due to the formation of a diazo intermediate which encounters a nucleophilic attack by carbonyl oxygen on the electrophilic amine to produce isoxazole products, as compared to the previous reportsa,b,4 in which an N-acylnitrenium ion intermediate is intramolecularly trapped by an amine group.

Bone marrow from blotchy mice is dispensable to regulate blood copper and aortic pathologies but required for inflammatory mediator production in LDLR-deficient mice during chronic angiotensin II infusion.

BACKGROUND: The blotchy mouse caused by mutations of ATP7A develops low blood copper and aortic aneurysm and rupture. Although the aortic pathologies are believed primarily due to congenital copper deficiencies in connective tissue, perinatal copper supplementation does not produce significant therapeutic effects, hinting additional mechanisms in the symptom development, such as an independent effect of the ATP7A mutations during adulthood. METHODS: We investigated if bone marrow from blotchy mice contributes to these symptoms. For these experiments, bone marrow from blotchy mice (blotchy marrow group) and healthy littermate controls (control marrow group) was used to reconstitute recipient mice (irradiated male low-density lipoprotein receptor -/- mice), which were then infused with angiotensin II (1,000 ng/kg/min) for 4 weeks. RESULTS: By using Mann-Whitney U test, our results showed that there was no significant difference in the copper concentrations in plasma and hematopoietic cells between these 2 groups. And plasma level of triglycerides was significantly reduced in blotchy marrow group compared with that in control marrow group (P < 0.05), whereas there were no significant differences in cholesterol and phospholipids between these 2 groups. Furthermore, a bead-based multiplex immunoassay showed that macrophage inflammatory protein (MIP)-1ß, monocyte chemotactic protein (MCP)-1, MCP-3, MCP-5, tissue inhibitor of metalloproteinases (TIMP)-1, and vascular endothelial growth factor (VEGF)-A production was significantly reduced in the plasma of blotchy marrow group compared with that in control marrow group (P < 0.05). More important, although angiotensin II infusion increased maximal external aortic diameters in thoracic and abdominal segments, there was no significant difference in the aortic diameters between these 2 groups. Furthermore, aortic ruptures, including transmural breaks of the elastic laminae in the abdominal segment and lethal rupture in the thoracic segment, were observed in blotchy marrow group but not in control marrow group; however, there was no significant difference in the incidence of aortic ruptures between these 2 groups (P = 0.10; Fisher's exact test). CONCLUSIONS: Overall, our study indicated that the effect of bone marrow from blotchy mice during adulthood is dispensable in the regulation of blood copper, plasma cholesterol and phospholipids levels, and aortic pathologies, but contributes to a reduction of MIP-1ß, MCP-1, MCP-3, MCP-5, TIMP-1, and VEGF-A production and triglycerides concentration in plasma. Our study also hints that bone marrow transplantation cannot serve as an independent treatment option.

Trends in the Main Residency Match From 2007 to 2020.

Background The United States Medical Licensing Exam (USMLE) Step 1 was recently changed from a numerically scored grading system to a pass/fail grading system. Until late 2024, there will be no formal studies about the impact that the grading change will have on the match process. To thoroughly assess the impact that this change will have on the overall match process, it is important to look at what the trends in applicants' objective measures have been in the years before the change. We aim to systematically evaluate the rates of change and mean trend of objective metrics found in residency applications in the main residency match.  Methods Objective medical student data of matched and unmatched applicants were queried from the National Matching Program's Charting Outcomes in the Match Reports for the 2007 to 2020 application cycles. Data were used to create linear regression analyses and statistical tests were performed to evaluate trends over time. Results For matched applicants, there were statistically significant positive trends for the mean number of contiguous ranks (m=0.33, p<0.01), having another non-doctoral graduate degree (m=0.67, p<0.01), membership to Alpha Omega Alpha (AOA) honor society (m=0.22, p<0.01), mean USMLE Step 1 score (m=1.01, p<0.01), mean USMLE Step 2 score (m=1.68, p<0.01), mean number of research experiences (m=0.12, p<0.01), and mean number of abstracts, presentations, and publications (m=0.34, p<0.01). Additionally, there was a statistically significant negative trend for the percentage who graduated from a top 40 National Institutes of Health-funded medical school (m=-0.41, p<0.01). For unmatched applicants, there were statistically significant positive trends for having another non-doctoral graduate degree (m=0.83, p<0.01), mean USMLE Step 1 score (m=1.26, p<0.01), mean USMLE Step 2 score (m=2.27, p<0.01), mean number of research experiences (m=0.13, p<0.01), and mean number of abstracts, presentations, and publications (m=0.33, p<0.01). Conclusion Our study shows that there have been statistically significant increases in almost all objective measures in the residency application. Recent changes to the abstracts, presentations, and publications on the Step 1 scoring system will force almost all residency programs to overhaul their application process and potentially increase reliance on Step 2, research, and other nonobjective factors. For students early in their medical education, emphasis on Step 2 and research will yield increased chances of matching into residency in the future.

Evaluating Urology Program Directors' Perception on Resident Application Parameters Following the Transition of USMLE Step 1 to Pass/Fail.

OBJECTIVE: To investigate how the shift of the United States Medical Licensing Examination (USMLE) Step 1 to a Pass/Fail (P/F) scoring system impacts the perceptions of Urology Program Directors (PDs) on evaluating urology residency applicants. METHODS AND MATERIALS: A cross-sectional survey was sent to 117 PDs, including questions about program characteristics, perceptions of shelf scores and medical school rank post-transition, beliefs about the predictive value of Step 1 and Step 2 Clinical Knowledge (CK) scores for board success and residency performance, and changes in applicant parameter ranking. RESULTS: Forty-five PDs (38% response rate) participated. Notably, 49% favored releasing quantitative clerkship grades, and 71% valued medical school rank more. Opinions on Step 1 scores' correlation with board success were split (49% agreed), and 44% endorsed Step 2 CK scores' connection to board performance. As predictors of good residents, only 9% and 22% considered Step 1 and Step 2 CK scores, respectively, indicative. Clerkship grades and Urology rotation recommendation letters maintained significance, while research experience gained importance. Step 2 CK scores' importance rose but did not match Step 1 scores' previous significance. CONCLUSION: The transition to P/F for USMLE Step 1 adds intricacies to urology residency selection, exposing PDs' uncertainties regarding clerkship grades and the relevance of medical school rank. This research underscores the dynamic nature of urology residency admissions, emphasizing the increasing importance of research in evaluating applicants and a diminishing emphasis on volunteering and leadership.

Risk factors for long COVID in children and adolescents: a systematic review and meta-analysis.

BACKGROUND: The long-term sequelae of COVID-19 in children and adolescents remain poorly understood and characterized. This systematic review and meta-analysis sought to summarize the risk factors for long COVID in the pediatric population. METHODS: We searched six databases from January 2020 to May 2023 for observational studies reporting on risk factors for long COVID or persistent symptoms those were present 12 or more weeks post-infection using multivariable regression analyses. Trial registries, reference lists of included studies, and preprint servers were hand-searched for relevant studies. Random-effects meta-analyses were conducted to pool odds ratios for each risk factor. Individual study risk of bias was rated using QUIPS, and the GRADE framework was used to assess the certainty of evidence for each unique factor. RESULTS: Sixteen observational studies (N = 46,262) were included, and 19 risk factors were amenable to meta-analysis. With moderate certainty in the evidence, age (per 2-year increase), allergic rhinitis, obesity, previous respiratory diseases, hospitalization, severe acute COVID-19, and symptomatic acute COVID-19 are probably associated with an increased risk of long COVID. Female sex, asthma, comorbidity, and heart diseases may be associated with an increased risk of long COVID, and Asian and Black races may be associated with a decreased risk of long COVID. We did not observe any credible subgroup effects for any risk factor. CONCLUSIONS: The current body of literature presents several compelling risk factors for the development of long COVID in the pediatric population. Further research is necessary to elucidate the pathophysiology of long COVID.

Assessing the debt and current state of financial literacy in a cohort of diagnostic & interventional radiology residents.

RATIONALE AND OBJECTIVES: The purpose of this study is to assess diagnostic and interventional radiology resident physicians' knowledge of core facets of financial literacy: loans, real estate, investments and retirement, and insurance, with the goal of determining the need for formal financial literacy education within radiology residency programs. METHODS: From May 2021 to March 2022, surveys were sent to 196 diagnostic and 90 interventional radiology residency programs. Residents were asked 10 knowledge multiple choice questions to assess areas of financial literacy. Custom R programming was used to evaluate responses. RESULTS: A total of 149 diagnostic radiology residents and 49 interventional radiology residents responded to portions of the survey, for a total of 198 respondents. Of the cohort with demographic data collected, 84 out of 141 residents (60 %) had over $100,000 of debt following medical school graduation, with 115 out of 146 DR residents (79 %) and 41 out of 47 (87 %) IR residents reporting no coursework in finance. CONCLUSIONS: Many radiology resident physicians have a significant debt burden, no official financial education, and clear knowledge gaps in areas of financial literacy. A structured financial education curriculum could better prepare residents for the financial realities of post-residency life.

Production of LPS-induced inflammatory mediators in murine peritoneal macrophages: neocuproine as a broad inhibitor and ATP7A as a selective regulator.

Copper chelation regulates the production of inflammatory mediators in vivo during vascular inflammation and atherogenesis. Little is known about how the copper egress pump ATP7A regulates the production of these mediators. In this study, we isolated ATP7A deficient macrophages (MΦ) from the peritoneal cavity of blotchy mice and identified the lipopolysaccharide (LPS)-induced inflammatory mediators that were altered by ATP7A deficiency. These results were compared with the effect of neocuproine (a copper chelator) treatment on both ATP7A deficient and control MΦ. Seven of the 24 inflammatory mediators examined in this study had significant changes in expression in the ATP7A deficient MΦ compared to controls; 16 of these mediators were significantly reduced in MΦ treated with neocuproine compared to controls. Both neocuproine treatment and ATP7A deficiency reduced IFN-γ, MCP-1, MCP-3, and VEGF-A levels. Interestingly, the production of KC/GRO was upregulated by ATP7A deficiency but downregulated by neocuproine treatment. Neocuproine, but not ATP7A deficiency, reduced the production of FGF-9, IL-1α, IL-12p70, IL-2, IL-3, IL-4, IL-6, MIP-1ß, MIP-2, RANTES, and TNFα. ATP7A deficiency but not neocuproine treatment reduced IP-10 and MCP-5 levels. In addition, both ATP7A deficiency and neocuproine treatment had no effect on GM-CSF, IL-10, IL-11, IL-7, OSM, and SCF. Together, these findings provide evidence that MΦ ATP7A selectively regulates LPS-induced inflammatory mediators, in part, via modulation of cellular copper availability, whereas neocuproine generally inhibits the production of inflammatory mediators. These results also imply that although copper chelation and ATP7A downregulation may result in different copper concentrations, gradients, and/or distribution in the cells, they may not lead to opposite biological effects on inflammatory mediator production.

Novel pain management therapies for patients with pemphigus.

Pemphigus is a class of rare autoimmune diseases that causes incredibly painful blistering of the skin and significantly impacts patients' day-to-day lives and well-being. Many strides have been made in treating pemphigus; however, no comprehensive literature exists on how to treat the pain that accompanies the disease. It is important to remember that treating pemphigus involves a two-fold treatment plan assessing both the underlying autoimmune disease and the pain involved with the lesions. This literature review explores novel therapies that have been shown to be effective in treating pain in pemphigus.

Perceptions of the Emergency Medicine Resident Selection Process by Program Directors Following the Transition to a Pass/Fail USMLE Step 1.

Background: Beginning January 26th, 2022, the National Board of Medical Examiners transitioned scoring of the United States Medical Licensing Examination (USMLE) Step 1 from a 3-digit score to pass/fail. In the past, the Step 1 score has been weighted heavily by program directors (PDs) as one of the most important metrics when assessing medical student's competitiveness. Objective: The objective of this study was to evaluate the perceptions of emergency medicine (EM) PDs on the transition to a pass/fail USMLE Step 1 exam, and to elicit the opinions of EM PDs on the USMLE examinations' ability to predict resident performance. Methods: A survey consisting of ranking and multiple-choice questions was sent to EM PDs. The multiple-choice questions were asked to determine EM PDs level of confidence in the ability of Step 1 and Step 2 Clinical Knowledge (CK) to predict a student's ability to succeed in residency. The ranking questions focused on assessing each program's current resident selection practices in comparison to expected selection criteria changes following a transition to pass/fail Step 1. R studio and MATLAB were used for statistical analysis, and a P value <0.05 was considered significant. Results: The survey was completed by 57 (20.21%) EM PDs. When asked if Step 1 and Step 2 CK are accurate predictors of a resident's ability to perform clinically within EM, only 10.5% of PDs answered 'yes' to Step 1 being predictive, compared to 31.6% for Step 2 CK. Regarding selection criteria, the top quartile of attributes (standardized letters of evaluation [1st], away rotations [2nd], clerkship grades [3rd] and Step 2 CK score [4th]) remained the same following the transition. Conclusion: Our results indicate that the top quartile of attributes might remain the same, despite most PDs agreeing that Step 2 CK is a better predictor of a resident's performance.

Interacting With Dermatology Patients Online: Private Practice vs Academic Institute Website Content.

Although both private practices and academic institutions in dermatology treat the same variety of pathologies, private practices entice more patients. The purpose of this study was to examine the differences in website content between dermatology private practices and academic institutions. All 140 dermatology residency programs were first queried. Only websites that contained pertinent information for patients were used in this study (113 of 140 programs). A total of 113 private practice websites were then matched for location and reputation. These sites were assessed for 23 content criteria categorized as practice, physician, patient, or treatment/procedure. The results may be useful for optimizing both private practice and academic institution websites so that patients can better understand the institutions that provide their care.

Evaluating the impact of pass/fail United States Medical Licensing Examination Step 1 scoring on pathology residency selection.

Beginning 26 January 2022, the United States Medical Licensing Examination Step 1 changed from a numerical score to Pass/Fail. Historically, residency programs have used Step 1 scores as a valuable metric in assessing the competitiveness of applicants. We assessed how residency program criteria will change when evaluating applicants after Step 1 becomes Pass/Fail. A survey was distributed to the program directors of all 144 pathology residency programs accredited by Accreditation Council for Graduate Medical Education. Survey questions evaluated the importance of using Step 1 and Step 2 Clinical Knowledge (CK) scores when assessing applicants. Participants were asked to rank a list of applicant criteria used before and after Step 1 becomes Pass/Fail. Data were analyzed using chi-squared and paired t-tests with significance at P < 0.05. A total of 34 residency program directors (23.6%) responded to the survey. 76.5% (P< 0.001) of responders believed Step 1 scores were able to predict a resident's ability to pass their board exams, while 41.2% believed Step 2 CK could predict a resident's ability to pass board exams and perform clinically in pathology (P = 0.282). 61.8% of responders agreed that an applicant's medical school ranking would become more important (P = 0.001). There were no significant differences in the relative importance of 16 selection criteria after the change of Step 1 to Pass/Fail. It does not appear that Step 2 CK will become more important. Although results are constrained by a 23.6% response rate, it can be a start to guiding future students through residency applications.

A Survey of Otolaryngology Residency Programs on Adapting to the United States Medical Licensing Examination (USMLE) Step 1 Transitioning to Pass/Fail.

Objectives In February 2020, the National Board of Medical Examiners (NBME) announced that the United States Medical Licensing Examination (USMLE) Step 1 licensing examination would change from a numerical score to Pass/Fail (P/F). After implementation, many believe that USMLE-Step 2-Clinical Knowledge (CK) will become an important metric for students applying to otolaryngology (ENT). The purpose of this study is to determine factors important to resident selection after these changes. Methods A survey containing 15 questions related to resident selection practices and how changing USMLE Step 1 to P/F would impact future resident selection was designed. It was distributed to all ENT residency programs accredited by the Accreditation Council for Graduate Medical Education (ACGME). Results Forty percent of programs responded; 66% (95% confidence interval (CI): 51.1%-78.4%) felt that changing Step 1 scoring would not lead to students being more prepared for clinical rotations; 55% believe class rank will increase in significance (95% CI: 35.7%-64.3%). There was also an increase in the importance of Step 2 CK, which had a mean ranking of 10.67 prior to changes in Step 1 scoring and increased to 7.80 after P/F. Conclusions The changes in Step 1 scoring will likely lead to increasing importance of other objective measures like class rank or Step 2 CK. This may defeat the intended purpose put forth by the NBME. Therefore, further guidance on measures correlated with student performance as a resident will be integral to the selection process.

Ophthalmology Residency Program Director Survey on Pass/Fail U.S. Medical Licensing Exam Step 1 Scoring.

Background Beginning January 26, 2022, the U.S. Medical Licensing Exam (USMLE) Step 1 changed from a numerical score to pass/fail (P/F). The purpose of this study was to determine the perspective of ophthalmology program directors regarding this change in evaluating applicants. Methods After institutional review board approval, a survey was sent out to program directors of all 125 ophthalmology programs accredited by the Accreditation Council for Graduate Medical Education. Survey questions asked for program demographics, the utility of USMLE Step 1 and 2 Clinical Knowledge scores in assessing applicants, and the importance of 16 different applicant metrics before and after Step 1 becomes P/F. The metrics examined were: letters of recommendation; clerkship grades; class ranking; Alpha Omega Alpha Membership; Gold Humanism Honor Society Membership; Dean's Letter; involvement and leadership; personal statement; number of abstracts, presentations, and publications; mean number of research experiences in the specialty; Step 2 Clinical Knowledge score; volunteering; preclinical grades; away rotation in the specialty; the applicant having another graduate degree; and graduation from a top 40 National Institutes of Health-funded program. Data were analyzed using nonoverlapping 95% confidence intervals. Results The survey was completed by 50 (40%) program directors. Sixty-eight percent of respondents stated a student's ranking would be considered more after USMLE Step 1 scores become P/F, and 60% stated medical schools should share clerkship shelf exam scores with residency programs. There were no significant differences in program directors' rankings of applicant metrics following the transition to P/F Step 1. Conclusion Based on our data, program directors will likely not place a greater emphasis on Step 2 scores, despite it being the only remaining objective measure for all applicants following the switch to a P/F Step 1. Nevertheless, program directors expressed an interest in receiving other objective measures, such as shelf exam scores and class ranking, as part of the application process. Notably, we found no significant changes in the rankings of various applicant metrics before and after the transition to P/F Step 1, indicating that the metrics that were important to program directors prior to the change remain just as critical in the new era of admissions.

Ex vivo study of molecular changes of stained teeth following hydrogen peroxide and peroxymonosulfate treatments.

White teeth can give confidence and tend to be associated with a healthier lifestyle in modern society. Therefore, tooth-bleaching strategies have been developed, including the use of hydrogen peroxide. Recently, peroxymonosulfate has been introduced as an alternative bleaching method to hydrogen peroxide. Although both chemicals are oxidizing agents, their effects on the molecular composition of the stained teeth are yet unknown. In this study, the molecular profiles of teeth bleached with hydrogen peroxide and peroxymonosulfate were compared using Liquid Chromatography-Tandem Mass Spectrometry. Statistical analyses were used to assess the samples. In addition, reference spectral libraries and in silico tools were used to perform metabolite annotation. Overall, principal component analysis showed a strong separation between control and hydrogen peroxide and peroxymonosulfate samples (p < 0.001). The analysis of molecular changes revealed amino acids and dipeptides in stained teeth samples after hydrogen peroxide and peroxymonosulfate treatments. Noteworthy, the two bleaching methods led to distinct molecular profiles. For example, diterpenoids were more prevalent after peroxymonosulfate treatment, while a greater abundance of alkaloids was detected after hydrogen peroxide treatment. Whereas non-bleached samples (controls) showed mainly lipids. Therefore, this study shows how two different tooth-whitening peroxides could affect the molecular profiles of human teeth.