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Article: A Novel MDM2-Binding Chalcone Induces Apoptosis of Oral Squamous Cell Carcinoma.

Wermelinger, Guilherme Freimann / Rubini, Lucas / da Fonseca, Anna Carolina Carvalho / Ouverney, Gabriel / de Oliveira, Rafael P R F / de Souza, Acácio S / Forezi, Luana S M / Limaverde-Sousa, Gabriel / Pinheiro, Sergio / Robbs, Bruno Kaufmann

Biomedicines

2023 Volume 11, Issue 6

Abstract: Oral squamous cell carcinoma (OSCC) represents ~90% of all oral cancers, being the eighth most common cancer in men. The overall 5-year survival rate is only 39% for metastatic cancers, and currently used chemotherapeutics can cause important side ... ...

Abstract	Oral squamous cell carcinoma (OSCC) represents ~90% of all oral cancers, being the eighth most common cancer in men. The overall 5-year survival rate is only 39% for metastatic cancers, and currently used chemotherapeutics can cause important side effects. Thus, there is an urgency in developing new and effective anti-cancer agents. As both chalcones and 1,2,3-triazoles are valuable pharmacophores/privileged structures in the search for anticancer compounds, in this work, new 1,2,3-triazole-chalcone hybrids were synthesized and evaluated against oral squamous cell carcinoma. By using different in silico, in vitro, and in vivo approaches, we demonstrated that compound
Language	English
Publishing date	2023-06-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11061711
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Article ; Online: All-cause and cause-specific mortality among people with bipolar disorder: a large-scale systematic review and meta-analysis.

Biazus, Taís Boeira / Beraldi, Gabriel Henrique / Tokeshi, Lucas / Rotenberg, Luísa de Siqueira / Dragioti, Elena / Carvalho, André F / Solmi, Marco / Lafer, Beny

Molecular psychiatry

2023 Volume 28, Issue 6, Page(s) 2508–2524

Abstract: Objective: Bipolar disorder (BD) is associated with premature mortality. All-cause and specific mortality risks in this population remain unclear, and more studies are still needed to further understand this issue and guide individual and public ... ...

Abstract	Objective: Bipolar disorder (BD) is associated with premature mortality. All-cause and specific mortality risks in this population remain unclear, and more studies are still needed to further understand this issue and guide individual and public strategies to prevent mortality in bipolar disorder Thus, a systematic review and meta-analysis of studies assessing mortality risk in people with BD versus the general population was conducted. The primary outcome was all-cause mortality, whilst secondary outcomes were mortality due to suicide, natural, unnatural, and specific-causes mortality. Results: Fifty-seven studies were included (BD; n = 678,353). All-cause mortality was increased in people with BD (RR = 2.02, 95% CI: 1.89-2.16, k = 39). Specific-cause mortality was highest for suicide (RR = 11.69, 95% CI: 9.22-14.81, k = 25). Risk of death due to unnatural causes (RR = 7.29, 95% CI: 6.41-8.28, k = 17) and natural causes (RR = 1.90, 95% CI: 1.75-2.06, k = 17) were also increased. Among specific natural causes analyzed, infectious causes had the higher RR (RR = 4,38, 95%CI: 1.5-12.69, k = 3), but the analysis was limited by the inclusion of few studies. Mortality risk due to respiratory (RR = 3.18, 95% CI: 2.55-3.96, k = 6), cardiovascular (RR = 1.76, 95% CI: 1.53-2.01, k = 27), and cerebrovascular (RR = 1.57, 95% CI: 1.34-1.84, k = 13) causes were increased as well. No difference was identified in mortality by cancer (RR = 0.99, 95% CI: 0.88-1.11, k = 16). Subgroup analyses and meta-regression did not affect the findings. Conclusion: Results presented in this meta-analysis show that risk of premature death in BD is not only due to suicide and unnatural causes, but somatic comorbidities are also implicated. Not only the prevention of suicide, but also the promotion of physical health and the prevention of physical conditions in individuals with BD may mitigate the premature mortality in this population. Notwithstanding this is to our knowledge the largest synthesis of evidence on BD-related mortality, further well-designed studies are still warranted to inform this field.
MeSH term(s)	Humans ; Bipolar Disorder/epidemiology ; Comorbidity ; Neoplasms/mortality ; Suicide ; Mortality
Language	English
Publishing date	2023-07-25
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	1330655-8
ISSN	1476-5578 ; 1359-4184
ISSN (online)	1476-5578
ISSN	1359-4184
DOI	10.1038/s41380-023-02109-9
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Article ; Online: The Brazilian version of the Inventory of Depression and Anxiety Symptoms-Expanded Version: Internal structure, invariance by sex and race, and associations with pathological personality traits.

Machado, Gisele Magarotto / Valentini, Felipe / Watson, David / Carvalho, Lucas de Francisco

Psychological assessment

2024 Volume 36, Issue 5, Page(s) e13–e26

Abstract: The Inventory of Depression and Anxiety Symptoms-Expanded version (IDAS-II) is one of the few tools designed to assess internalizing symptoms based on dimensional models. We conducted two studies, the first testing internal validity aspects of the IDAS- ... ...

Abstract	The Inventory of Depression and Anxiety Symptoms-Expanded version (IDAS-II) is one of the few tools designed to assess internalizing symptoms based on dimensional models. We conducted two studies, the first testing internal validity aspects of the IDAS-II and the second testing the external validity of the scales. In the first study we adapted the IDAS-II to Brazilian Portuguese and tested its internal structure, including a higher order factorial solution coherent with the internalizing spectrum, the stability of the factor structure, and its measurement invariance for sex and racial groups. Participants were 2,379 Brazilian adults. In the second study, we investigated the IDAS-II scales' associations with broad pathological personality traits in Brazilian (
MeSH term(s)	Humans ; Male ; Female ; Brazil ; Adult ; Young Adult ; Middle Aged ; Psychometrics ; Reproducibility of Results ; Anxiety/psychology ; Anxiety/diagnosis ; Depression/psychology ; Depression/diagnosis ; Psychiatric Status Rating Scales/standards ; Sex Factors ; Factor Analysis, Statistical ; Personality Disorders/diagnosis ; Personality Disorders/psychology ; Adolescent ; Anxiety Disorders/diagnosis ; Anxiety Disorders/psychology ; Aged ; Personality Inventory
Language	English
Publishing date	2024-04-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	1000939-5
ISSN	1939-134X ; 1040-3590
ISSN (online)	1939-134X
ISSN	1040-3590
DOI	10.1037/pas0001312
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Zs.A 2645: Show issues

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Article ; Online: Human Exposure to Non-Ionizing Radiation from Indoor Distributed Antenna System: Shopping Mall Measurement Analysis.

da L A Silva, Júlia / de Sousa, Vicente A / Rodrigues, Marcio E C / Pinheiro, Fred Sizenando Rossiter / da Silva, Gutembergue Soares / Mendonça, Halysson B / de F H Silva, Ricardo Q / da Silva, João V L / Galdino, Fernanda E S / de Carvalho, Vitor F C / Medeiros, Lucas I C

Sensors (Basel, Switzerland)

2023 Volume 23, Issue 10

Abstract: It is crucial to monitor the levels of Non-Ionizing Radiation (NIR) to which the general population may be exposed and compare them to the limits defined in the current standards, in view of the rapid rise of communication services and the prospects of a ...

Abstract	It is crucial to monitor the levels of Non-Ionizing Radiation (NIR) to which the general population may be exposed and compare them to the limits defined in the current standards, in view of the rapid rise of communication services and the prospects of a connected society. A high number of people visits shopping malls and since these locations usually have several indoor antennas close to the public, it is therefore a kind of place that must be evaluated. Thus, this work presents measurements of the electric field in a shopping mall located in Natal, Brazil. We proposed a set of six measurement points, following two criteria: places with great the flow of people and the presence of one or more Distributed Antenna System (DAS), co-sited or not with WiFi access points. Results are presented and discussed in terms of the distance to DAS (conditions: near and far) and flow density of people in the mall (scenarios: low and high number of people). The highest peaks of electric field measured were 1.96 and 3.26 V/m, respectively corresponding to 5% and 8% of the limits defined by the International Commission on Non-Ionizing Radiation Protection (ICNIRP) and the Brazilian National Telecommunication Agency (ANATEL).
MeSH term(s)	Humans ; Brazil ; Electricity ; Telecommunications ; Radiation, Nonionizing
Language	English
Publishing date	2023-05-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2052857-7
ISSN	1424-8220 ; 1424-8220
ISSN (online)	1424-8220
ISSN	1424-8220
DOI	10.3390/s23104579
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Article ; Online: Feasibility of Transatrial Access for Epicardial Ablation: Evaluation of 2 Different Techniques in Swine.

Chokr, Muhieddine O / Pinto Vandoni, Pedro Mario / de Carvalho Neto, Jose Nilo / de Moura, Lucas G / Dos Santos Sousa, Italo Bruno / Aiello, Vera D / de Brito, Fabio Sandoli / Pisani, Cristiano F / Hardy, Carina A / de Melo, Sissy L / Darrieux, Francisco C C / Hachul, Denise T / Scanavacca, Mauricio I

JACC. Clinical electrophysiology

2023 Volume 9, Issue 11, Page(s) 2315–2328

Abstract: Background: The subxiphoid pericardial access is technically difficult and has a considerable rate of complications, thus transatrial access may be an alternative.: Objectives: This study sought to assess the feasibility and safety of this strategy ... ...

Abstract	Background: The subxiphoid pericardial access is technically difficult and has a considerable rate of complications, thus transatrial access may be an alternative. Objectives: This study sought to assess the feasibility and safety of this strategy regarding periprocedural period and after 1-week follow-up. Methods: The investigators performed epicardial mapping through transatrial puncture in 20 swine. Animals were divided into group A, in which aspiration of the sheath was performed to maintain negative pressure after the withdraw of the catheters, and group B, in which a device (Konar-MF VSD Occluder) was delivered to occlude the right atrial appendage perforation. Bleeding was investigated immediately and 1 week after. Results: Access was safe in 19 of 20 animals (95%) with small amount of bleeding (6.4 ± 6 mL). In group A (n = 10), 1 animal presented hemopericardium right after the puncture. In the other 9, epicardial ablation was performed and 60.0 ± 28.0 mL of blood was aspirated without events. After 1 week, fibrin-hemorrhagic pericarditis was identified in 3 animals. In group B (n = 10), reaching the epicardial surface was possible in all animals. An adequate position of the prosthesis was obtained in 90% (9 of 10). One death occurred in the immediate postoperative period, secondary to pneumothorax. After 1 week, postmortem analysis showed absence of pericardial bleeding and a normal-appearing pericardium in the 8 animals with adequate prosthesis position. Conclusions: Transatrial access allows epicardial mapping and ablation. Sheath removal after negative pressure contributes to achieving acute bleeding control but does not prevent its occurrence. The use of the device prevents bleeding and hemorrhagic pericarditis.
MeSH term(s)	Animals ; Swine ; Feasibility Studies ; Epicardial Mapping/methods ; Pericardium/surgery ; Pericarditis ; Hemorrhage/etiology
Language	English
Publishing date	2023-09-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2846739-5
ISSN	2405-5018 ; 2405-500X ; 2405-500X
ISSN (online)	2405-5018 ; 2405-500X
ISSN	2405-500X
DOI	10.1016/j.jacep.2023.07.015
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Article ; Online: Chemoselective Synthesis of Mannich Adducts from 1,4-Naphthoquinones and Profile as Autophagic Inducers in Oral Squamous Cell Carcinoma.

Borges, Amanda A / de Souza, Michele P / da Fonseca, Anna Carolina C / Wermelinger, Guilherme F / Ribeiro, Ruan C B / Amaral, Adriane A P / de Carvalho, Cláudio José C / Abreu, Lucas S / de Queiroz, Lucas Nicolau / de Almeida, Elan C P / Rabelo, Vitor W / Abreu, Paula A / Pontes, Bruno / Ferreira, Vitor F / da Silva, Fernando de C / Forezi, Luana da S M / Robbs, Bruno K

Molecules (Basel, Switzerland)

2022 Volume 28, Issue 1

Abstract: Oral squamous cell carcinoma (OSCC) is a worldwide public health problem, accounting for approximately 90% of all oral cancers, and is the eighth most common cancer in men. Cisplatin and carboplatin are the main chemotherapy drugs used in the clinic. ... ...

Abstract	Oral squamous cell carcinoma (OSCC) is a worldwide public health problem, accounting for approximately 90% of all oral cancers, and is the eighth most common cancer in men. Cisplatin and carboplatin are the main chemotherapy drugs used in the clinic. However, in addition to their serious side effects, such as damage to the nervous system and kidneys, there is also drug resistance. Thus, the development of new drugs becomes of great importance. Naphthoquinones have been described with antitumor activity. Some of them are found in nature, but semi synthesis has been used as strategy to find new chemical entities for the treatment of cancer. In the present study, we promote a multiple component reaction (MCR) among lawsone, arylaldehydes, and benzylamine to produce sixteen chemoselectively derivated Mannich adducts of 1,4-naphthoquinones in good yield (up to 97%). The antitumor activities and molecular mechanisms of action of these compounds were investigated in OSCC models and the compound 6a induced cytotoxicity in three different tumor cell lines (OSCC4, OSCC9, and OSCC25) and was more selective (IS > 2) for tumor cells than the chemotropic drug carboplatin and the controls lapachol and shikonin, which are chemically similar compounds with cytotoxic effects. The 6a selectively and significantly reduced the amount of cell colony growth, was not hemolytic, and tolerable in mice with no serious side effects at a concentration of 100 mg/kg with a LD50 of 150 mg/kg. The new compound is biologically stable with a profile similar to carboplatin. Morphologically, 6a does not induce cell retraction or membrane blebs, but it does induce intense vesicle formation and late emergence of membrane bubbles. Exploring the mechanism of cell death induction, compound 6a does not induce ROS formation, and cell viability was not affected by inhibitors of apoptosis (ZVAD) and necroptosis (necrostatin 1). Autophagy followed by a late apoptosis process appears to be the death-inducing pathway of 6a, as observed by increased viability by the autophagy inhibitor (3-MA) and by the appearance of autophagosomes, later triggering a process of late apoptosis with the presence of caspase 3/7 and DNA fragmentation. Molecular modeling suggests the ability of the compound to bind to topoisomerase I and II and with greater affinity to hPKM2 enzyme than controls, which could explain the mechanism of cell death by autophagy. Finally, the in-silico prediction of drug-relevant properties showed that compound 6a has a good pharmacokinetic profile when compared to carboplatin and doxorubicin. Among the sixteen naphthoquinones tested, compound 6a was the most effective and is highly selective and well tolerated in animals. The induction of cell death in OSCC through autophagy followed by late apoptosis possibly via inhibition of the PKM2 enzyme points to a promising potential of 6a as a new preclinical anticancer candidate.
MeSH term(s)	Animals ; Mice ; Carcinoma, Squamous Cell/pathology ; Squamous Cell Carcinoma of Head and Neck/drug therapy ; Mouth Neoplasms/metabolism ; Carboplatin/pharmacology ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Apoptosis ; Cell Line, Tumor ; Head and Neck Neoplasms/drug therapy ; Autophagy ; Naphthoquinones/chemistry
Chemical Substances	Carboplatin (BG3F62OND5) ; Antineoplastic Agents ; Naphthoquinones
Language	English
Publishing date	2022-12-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules28010309
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Article ; Online: Telomeric repeat-containing RNA is dysregulated in acute myeloid leukemia.

Catto, Luiz Fernando B / Zanelatto, Leonardo C / Donaires, Flavia S / de Carvalho, Vinicius S / Santana, Bárbara A / Pinto, André L / Fantacini, Daianne / de Souza, Lucas Eduardo B / Fonseca, Natasha P / Telho, Bruno S / Ayrosa Madeira, Maria Isabel / Barbosa Pagnano, Katia Borgia / Firmato, Ana Beatriz / Fagundes, Evandro Maranhão / Higashi, Marcia / Nunes, Elenaide Coutinho / Traina, Fabiola / Lobo de F Pontes, Lorena / Rego, Eduardo M /

Calado, Rodrigo T

Blood advances

2023 Volume 7, Issue 22, Page(s) 7067–7078

Abstract: TERRA (telomeric repeat-containing RNA) is a class of long noncoding RNAs transcribed from subtelomeric and telomeric regions. TERRA binds to the subtelomeric and telomeric DNA-forming R-loops (DNA-RNA hybrids), which are involved in telomere maintenance ...

Abstract	TERRA (telomeric repeat-containing RNA) is a class of long noncoding RNAs transcribed from subtelomeric and telomeric regions. TERRA binds to the subtelomeric and telomeric DNA-forming R-loops (DNA-RNA hybrids), which are involved in telomere maintenance and telomerase function, but the role of TERRA in human cells is not well characterized. Here, we comprehensively investigated for the first time TERRA expression in primary human hematopoietic cells from an exploratory cohort of patients with acute myeloid leukemia (AML), patients with acute lymphoblastic leukemia (ALL), patients with telomere biology disorder (TBD), and healthy subjects. TERRA expression was repressed in primary human hematopoietic cells, including healthy donors, patients with ALL, and patients with TBD, irrespective of their telomere length, except for AML. A second cohort comprising 88 patients with AML showed that TERRA was overexpressed in an AML subgroup also characterized by higher R-loop formation, low TERT and RNAseH2 expression, and a paucity of somatic splicing factor mutations. Telomere length did not correlate with TERRA expression levels. To assess the role of TERRA R-loops in AML, we induced R-loop depletion by increasing RNAseH1 expression in 2 AML cell lines. Decreased TERRA R-loops in AML cell lines resulted in increased chemosensitivity to cytarabine. Our findings indicate that TERRA is uniformly repressed in primary human hematopoietic cells but abnormally expressed in an AML subset with low telomerase.
MeSH term(s)	Humans ; Telomerase ; Leukemia, Myeloid, Acute/genetics ; Cell Line ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; RNA, Long Noncoding ; DNA
Chemical Substances	Telomerase (EC 2.7.7.49) ; RNA, Long Noncoding ; DNA (9007-49-2)
Language	English
Publishing date	2023-09-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2023010658
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Article ; Online: Highly effective adsorption of caffeine by a novel activated carbon prepared from coconut leaf.

Oliveira, Elvio N / Meneses, Alex T / de Melo, Samara F / Dias, Franciele M R / Perazzini, Maisa T B / Perazzini, Hugo / Meili, Lucas / Soletti, João I / Carvalho, Sandra H V / Bispo, Mozart D

Environmental science and pollution research international

2022 Volume 29, Issue 33, Page(s) 50661–50674

Abstract: The disposal of coconut wastes is costly and damaging to the environment, but its uses are advantageous activated carbons production. Coconut leaves waste were used for activated carbon production by pyrolysis at 500° C and activation with potassium ... ...

Abstract	The disposal of coconut wastes is costly and damaging to the environment, but its uses are advantageous activated carbons production. Coconut leaves waste were used for activated carbon production by pyrolysis at 500° C and activation with potassium carbonate. The activated carbon was used for caffeine removal from aqueous solution. The coconut leaves activated carbon showed a predominantly amorphous structure from X-ray diffraction analysis and a pH at the zero charge point of 7.9. From the N
MeSH term(s)	Adsorption ; Caffeine/analysis ; Charcoal/chemistry ; Cocos/chemistry ; Hydrogen-Ion Concentration ; Kinetics ; Plant Leaves/chemistry ; Thermodynamics ; Water/analysis ; Water Pollutants, Chemical/analysis ; Water Purification/methods
Chemical Substances	Water Pollutants, Chemical ; Water (059QF0KO0R) ; Charcoal (16291-96-6) ; Caffeine (3G6A5W338E)
Language	English
Publishing date	2022-03-02
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1178791-0
ISSN	1614-7499 ; 0944-1344
ISSN (online)	1614-7499
ISSN	0944-1344
DOI	10.1007/s11356-022-18788-w
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Article ; Online: Degradation of xanthene-based dyes by photoactivated persulfate: experimental and computational studies.

do Nascimento, Carlos Pedro G / Costa, Mateus S M A / Freire, Jessica M A / da Silva, Luiz Thiago V / Coutinho, Lucas P / Monteiro, Norberto K V / Zampieri, Dávila de S / Oliveira, Juliene T / do Nascimento, Ronaldo F / de Carvalho, Idalina M M / Becker, Helena / Longhinotti, Elisane

Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology

2023 Volume 22, Issue 12, Page(s) 2699–2714

Abstract: Dyes are naked-eye detectable even at low concentration levels and can cause environmental damage when released into aquatic effluents; therefore, methods for removing the residual color from the aquatic media are always a current issue. In this paper, ... ...

Abstract	Dyes are naked-eye detectable even at low concentration levels and can cause environmental damage when released into aquatic effluents; therefore, methods for removing the residual color from the aquatic media are always a current issue. In this paper, degradation of three xanthene dyes, Rhodamine B, Eosin Y, and Sodium Fluorescein, using photoactivated persulfate was evaluated at pH 3.0 and 11.0. The dyes' degradation followed a pseudo-first-order reaction. Although the solution is completely decolorized in 40 min at pH 3.0, achieving 75% mineralization requires a longer reaction time of 180 min. Furthermore, GC-MS analyses indicate that degradation products are mainly low-molecular weight acids, CO
Language	English
Publishing date	2023-09-23
Publishing country	England
Document type	Journal Article
ZDB-ID	2072584-X
ISSN	1474-9092 ; 1474-905X
ISSN (online)	1474-9092
ISSN	1474-905X
DOI	10.1007/s43630-023-00480-8
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Article ; Online: A Novel MDM2-Binding Chalcone Induces Apoptosis of Oral Squamous Cell Carcinoma

Guilherme Freimann Wermelinger / Lucas Rubini / Anna Carolina Carvalho da Fonseca / Gabriel Ouverney / Rafael P. R. F. de Oliveira / Acácio S. de Souza / Luana S. M. Forezi / Gabriel Limaverde-Sousa / Sergio Pinheiro / Bruno Kaufmann Robbs

Biomedicines, Vol 11, Iss 1711, p

2023 Volume 1711

Abstract	Oral squamous cell carcinoma (OSCC) represents ~90% of all oral cancers, being the eighth most common cancer in men. The overall 5-year survival rate is only 39% for metastatic cancers, and currently used chemotherapeutics can cause important side effects. Thus, there is an urgency in developing new and effective anti-cancer agents. As both chalcones and 1,2,3-triazoles are valuable pharmacophores/privileged structures in the search for anticancer compounds, in this work, new 1,2,3-triazole-chalcone hybrids were synthesized and evaluated against oral squamous cell carcinoma. By using different in silico, in vitro, and in vivo approaches, we demonstrated that compound 1f has great cytotoxicity and selectivity against OSCC (higher than carboplatin and doxorubicin) and other cancer cells in addition to showing minimal toxicity in mice. Furthermore, we demonstrate that induced cell death occurs by apoptosis and cell cycle arrest at the G2/M phase. Moreover, we found that 1f has a potential affinity for MDM2 protein, similar to the known ligand nutlin-3, and presents a better selectivity, pharmacological profile, and potential to be orally absorbed and is not a substrate of Pg-P when compared to nutlin-3. Therefore, we conclude that 1f is a good lead for a new chemotherapeutic drug against OSCC and possibly other types of cancers.
Keywords	chalcone ; 1,2,3-triazole ; MDM2 ; p53 ; antitumor ; oral squamous cell carcinoma ; Biology (General) ; QH301-705.5
Subject code	500
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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