Novel 2-(R-phenyl)amino-3-(2-methylpropenyl)-[1,4]-naphthoquinones: synthesis, characterization, electrochemical behavior and antitumor activity

Novel 2-(R-phenyl)amino-3-(2-methyl-propenyl)-[1,4]-naphthoquinones (R = H, 4-OMe, 4-Ferrocenyl, 4-Me, 3-Me, 4-I, 3-I, 4-CN, 3-CN, 4-NO2 and 3-NO2) derived from nor-lapachol [2-hydroxy-3-(2-methylpropenyl)-1,4-naphthoquinone] were obtained in good yields. Their structures were proposed on the basis of a single crystal X-ray diffraction study (R = OMe, 2b), ¹H and 13C NMR studies and calculations using the B3LYP functional and the 6-311+G(2d,p) basis set. The half-wave potentials of the aminonaphthoquinones and ¹H NMR chemical shifts of the 3-propenyl hydrogen in 2a-k show good correlation with the substituent Hammett constants on the phenylamino ring. The antitumor assays showed promising activity for substrate methoxy-nor-lapachol 1 and the 4-ferrocenyl derivative 2c.Novas 2-(R-fenil)amino-3-(2-metilpropenil)-[1,4]-naftoquinonas (R = H, 4-OMe, 4-Ferrocenil, 4-Me, 3-Me, 4-I, 3-I, 4-CN, 3-CN, 4-NO2 e 3-NO2) derivadas do nor-lapachol [2-hidroxi-3-(2-metilpropenil)-1,4-naftoquinona] foram obtidas em bons rendimentos. A estrutura dos compostos foi proposta com base em estudos de difração de raios-X (R = OMe, 2b), dados de RMN de ¹H e 13C e cálculos teóricos utilizando o funcional B3LYP e a base 6-311+G(2d,p). Os potenciais de meia-onda das aminonaftoquinonas e o deslocamento químico do hidrogênio da cadeia 3-propenil dos compostos 2a-k mostraram boa correlação com as constantes de Hammett dos substituintes presentes no anel fenileno. A avaliação da citotoxicidade evidenciou atividade antitumoral promissora para o substrato metóxi-nor-lapachol 1 e o derivado 4-ferrocenil 2c.169178Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

First report of severe acute respiratory syndrome coronavirus 2 detection in two asymptomatic cats in the state of Pernambuco, Northeastern Brazil

Background and Aim: Despite worldwide case reports, including Brazilian cases, no frequency study on infection of pets by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been conducted to date in Brazil. Accordingly, the present study was aimed to assess dogs and cats belonging to positive owners in Recife, Northeastern Brazil. Materials and Methods: This was a longitudinal prospective study on dogs and cats in the city of Recife whose owners were in isolation at home due to a confirmed laboratory diagnosis of SARS-CoV-2 through reverse-transcriptase polymerase chain reaction (RT-qPCR). Oral and rectal swabs from the pets were tested for the presence of SARS-CoV-2-specific RNA by means of RT-qPCR. Results: Among the pets tested, 0/16 dogs and 2/15 cats were positive for SARS-CoV-2. Interestingly, the two positive cats were owned by two unrelated asymptomatic veterinary students, which, therefore, post a warning to veterinarians worldwide. Conclusion: The findings herein indicate that cats may act as sentinels for human cases, particularly sharing households with asymptomatic human cases. Although with small sampling and convenient recruiting, the presence of infected cats by SARS-CoV-2 was most likely due to close cat-human contact with positive owners, posting a human-animal health threat when pets share the same bed and interact with owners without protection, particularly during owner self-isolation. Thus, infected owners should follow the same human preventive guidelines with their pets to avoid spreading infection

Pisosterol induces G2/M cell cycle arrest and apoptosis via the ATM/ATR signaling pathway in human glioma cells

Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Cultura de Tecidos e Citogenética Ananindeua, PA, Brasil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Citogenética Humana. Belém, PA, Brazil.Universidade Federal do Ceará. Departamento de Fisiologia e Farmacologia. Fortaleza, CE, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Biologia Molecular Francisco Mauro Salzano. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Biologia Molecular Francisco Mauro Salzano. Belém, PA, Brazil.Universidade Federal do Pará. Faculdade de Ciências Naturais. Instituto de Ciências Exatas e Naturais. Belém, PA, Brazil.Background: Pisosterol, a triterpene derived from Pisolithus tinctorius, exhibits potential antitumor activity in various malignancies. However, the molecular mechanisms that mediate the pisosterol-specific effects on glioma cells remain unknown. Objective: This study aimed to evaluate the antitumoral effects of pisosterol on glioma cell lines. Methods: The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and trypan blue exclusion assays were used to evaluate the effect of pisosterol on cell proliferation and viability in glioma cells. The effect of pisosterol on the distribution of the cells in cell cycle was performed by flow cytometry. The expression and methylation pattern of the promoter region of MYC, ATM, BCL2, BMI1, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, MDM2, p14ARF and TP53 was analyzed by RT-qPCR, western blotting and bisulfite sequencing PCR (BSP-PCR). Results: Here, we reported that pisosterol markedly induced G2/M arrest and apoptosis and decreased the cell viability and proliferation potential of glioma cells in a dose-dependent manner by increasing the expression of ATM, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, p14ARF and TP53 and decreasing the expression of MYC, BCL2, BMI1 and MDM2. Pisosterol also triggered both caspase-independent and caspase-dependent apoptotic pathways by regulating the expression of Bcl-2 and activating caspase-3 and p53. Conclusions: We, for the first time, confirmed that the ATM/ATR signaling pathway is a critical mechanism for G2/M arrest in pisosterol-induced glioma cell cycle arrest and suggest that this compound might be a promising anticancer candidate for further investigation

Synthesis and evaluation of cytotoxic activity derived 2,3-diyne-1,4-naphthoquinones

In the present study ten 2,3-diyne-1,4-naphthoquinone derivatives (3a-j) were synthesized by Sonogashira coupling reaction between the 2,3-dibromo-1,4-naphthoquinone (2) and several functionalized terminal alkynes using a catalytic complex of palladium (II) and CuI. Alkynes are among phenylacetylene, 1-ethyl-4-methoxybenzene, 2-methyl-3-butyn-2-ol, 1-ethynyl-1-cyclohexanol, 4-pentyn-2-ol, 4-pentyn-1-ol, 1-pentyne, 1-hexyne, 1-decyne and 1-octyne. The yields of products obtained ranged 15 to 55%. The enediynes having hydroxyl groups, in their structures such as 2,3-di(3-hydroxy-3-methylbut-1-in-1-yl)-, 2,3-di[(1-hydroxycyclohexyl)ethynyl]- and 2,3-di(5-hydroxypent-1-yl)-1,4-naphthoquinone were subjected to acetylation reaction using acetic anhydride and montmorillonite clay K-10 under sonication, thereby obtaining three new enediyne derivatives (3c’, d’ and f’) with yields ranging from 56 to 71%. The compounds were all characterized by 1H NMR and 13C NMR spectra, IR and MS-LC. These compounds containing the 1,4-naphthoquinone nucleus and acetylenic substituents in the quinonoid ring form a enediyne system (Z-3-ene-1,5-diyne) highly reactive, possibly subject to Bergman cycloaromatization, with potential antitumor activity. The enediynes underwent evaluation of the cytotoxic potential against three tumor cell lines, OVCAR-8 (ovarian adenocarcinoma - human), PC-3M (metastatic prostate cancer - human), NCI-H358M (bronchoalveolar lung carcinoma - human), presenting, in general, satisfactory results for inhibition of cell growth. The compound 2,3-di(3-hydroxy-3-methylbut-1-in-yl)-1,4-naphthoquinone (3c) where said among the substances analyzed by presenting a lower IC50 (˂ 2 µg/mL) for three cell lines tested, which is characterized as a potent cytotoxic agent.</p