Click-chemistry mediated synthesis of OTBN-1,2,3-Triazole derivatives exhibiting STK33 inhibition with diverse anti-cancer activities.

There is a continuous and pressing need to establish new brain-penetrant bioactive compounds with anti-cancer properties. To this end, a new series of 4'-((4-substituted-4,5-dihydro-1H-1,2,3-triazol-1-yl)methyl)-[1,1'-biphenyl]-2-carbonitrile (OTBN-1,2,3-triazole) derivatives were synthesized by click chemistry. The series of bioactive compounds were designed and synthesized from diverse alkynes and N3-OTBN, using copper (II) acetate monohydrate in aqueous dimethylformamide at room temperature. Besides being highly cost-effective and significantly reducing synthesis, the reaction yielded 91-98 % of the target products without the need of any additional steps or chromatographic techniques. Two analogues exhibit promising anti-cancer biological activities. Analogue 4l shows highly specific cytostatic activity against lung cancer cells, while analogue 4k exhibits pan-cancer anti-growth activity. A kinase screen suggests compound 4k has single-digit micromolar activity against kinase STK33. High STK33 RNA expression correlates strongly with poorer patient outcomes in both adult and pediatric glioma. Compound 4k potently inhibits cell proliferation, invasion, and 3D neurosphere formation in primary patient-derived glioma cell lines. The observed anti-cancer activity is enhanced in combination with specific clinically relevant small molecule inhibitors. Herein we establish a novel biochemical kinase inhibitory function for click-chemistry-derived OTBN-1,2,3-triazole analogues and further report their anti-cancer activity in vitro for the first time.

Alkoxy-functionalised dihydropyrimido[4,5-b]quinolinones enabling anti-proliferative and anti-invasive agents.

In this communication, we explored the synthesis of novel alkoxy-functionalised dihydropyrimido[4,5-b]quinolinones using a microwave-assisted multicomponent reaction. All the synthesized molecules were screened for anti-proliferative and anti-invasive activity against glioblastoma cells. 5c shows the most potent anti-proliferative activity with a half maximal effective concentration of less than 3 µM against primary patient-derived glioblastoma cells. 5c effectively inhibited invasion and tumor growth of 3D primary glioma cultures in a basement membrane matrix. This suggests that the novel compounds could inhibit both the proliferation and invasive spread of glioma and they were selected for further study.

A green bio-organic catalyst (taurine) promoted one-pot synthesis of (R/S)-2-thioxo-3,4-dihydropyrimidine(TDHPM)-5-carboxanilides: chiral investigations using circular dichroism and validation by computational approaches.

Owing to the massive importance of dihydropyrimidine (DHPMs) scaffolds in the pharmaceutical industry and other areas, we developed an effective and sustainable one-pot reaction protocol for the synthesis of (R/S)-2-thioxo-DHPM-5-carboxanilides via the Biginelli-type cyclo-condensation reaction of aryl aldehydes, thiourea and various acetoacetanilide derivatives in ethanol at 100 °C. In this protocol, taurine was used as a green and reusable bio-organic catalyst. Twenty-three novel derivatives of (R/S)-TDHPM-5-carboxanilides and their structures were confirmed by various spectroscopy techniques. The aforementioned compounds were synthesized via the formation of one asymmetric centre, one new C-C bond, and two new C-N bonds in the final product. All the newly synthesized compounds were obtained in their racemic form with up to 99% yield. In addition, the separation of the racemic mixture of all the newly synthesized compounds was carried out by chiral HPLC (Prep LC), which provided up to 99.99% purity. The absolute configuration of all the enantiomerically pure isomers was determined using a circular dichroism study and validated by a computational approach. With up to 99% yield of 4d, this one-pot synthetic approach can also be useful for large-scale industrial production. One of the separated isomers (4R)-(+)-4S developed as a single crystal, and it was found that this crystal structure was orthorhombic.

Masking our emotions: Emotion recognition and perceived intensity differ by race and use of medical masks.

Although medical masks have played a key role in decreasing the transmission of communicable disease, they simultaneously reduce the availability of nonverbal cues fundamental to social interaction. In the present study, we determined the collective impact of medical masks on emotional expression recognition and perceived intensity as a function of actor race. Participants completed an emotional expression recognition task involving stimuli with or without medical masks. Across six basic emotional facial expressions, medical masks were associated with significantly more emotional expression recognition errors. Overall, the effects associated with race varied depending on the emotion and appearance of masks. Whereas recognition accuracy was higher for White relative to Black actors for anger and sadness, the opposite pattern was observed for disgust. Medical mask-wearing exacerbated actor-race related recognition differences for anger and surprise, but attenuated these differences for fear. Emotional expression intensity ratings were significantly reduced for all emotions except fear, where masks were associated with increased perceived intensity. Masks further increased already higher intensity ratings for anger in Black versus White actors. In contrast, masks eliminated the tendency to give higher intensity ratings for Black versus White sad and happy facial expressions. Overall, our results suggest that the interaction between actor race and mask wearing status with respect to emotional expression judgements is complex, varying by emotion in both direction and degree. We consider the implications of these results particularly in the context of emotionally charged social contexts, such as in conflict, healthcare, and policing.

Functional Characterization of Lactobacillus plantarum Isolated from Cow Milk and the Development of Fermented Coconut and Carrot Juice Mixed Beverage.

Screening probiotics are crucial for assessing their safety, security, and further production of functional foods for human health. The present study aimed to isolate and identify bacteria from raw cow's milk samples that exhibit health benefits upon consumption. We characterized the probiotic properties of Lactobacillus plantarum (also called Lactiplantibacillus plantarum) strains CMGC2 and CMJC7 isolated from cow milk by in vitro study. The strains exhibited tolerance to simulated gastric conditions and were further identified by 16S rRNA sequencing as Lactobacillus plantarum (L. plantarum) CMGC2 and CMJC7. Both isolates were evaluated in vitro for their probiotic attributes, viz. hydrophobicity, autoaggregation, co-aggregation, lysozyme tolerance, antibacterial activity, antibiotic susceptibility, hemolytic activity, and phenol tolerance. The isolates CMGC2 and CMJC7 showed excellent probiotic attributes; hence, both strains were selected to produce coconut and carrot juice mixed beverages (CCMB). The CCMB was evaluated for the pH, acid-production rate, and total viable bacterial counts. The results showed that the CCMB was an excellent medium for the growth of CMGC2 and CMJC7 as it supported adequate growth of organisms (8.93 CFU/mL and 8.68 CFU/mL, respectively) even after 48 h of incubation. In conclusion, CMGC2 and CMJC7 can be used to develop different beverages possessing nutritive and probiotic values, and these beverages can be used for producing unique products.

Beneficial effect of polyherbal formulation in letrozole induced Polycystic ovarian syndrome (PCOS).

Aim of the study: PCOS is an endocrine condition that results in enlarged ovaries with tiny cysts on the margins. The present study aims to investigate the beneficial effect of polyherbal formulation in Letrozole induced PCOS in female Albino Wistar rats. Materials and methods: Acute toxicity study of the polyherbal formulation by administering a single dose (2000 mg/kg) was done in female Albino Wistar rats (20 weeks, 250 g) following OECD guideline 423. For PCOS induced study female Albino Wistar rats were divided into six groups (6 animals/group). Group I (control) was given 0.5% carboxymethylcellulose (CMC) suspension daily as vehicle control. Letrozole (1 mg/kg) was orally administered for 21 days in Group II to VI for induction of PCOS. After induction of PCOS, animals were treated with standard drug (Group III- Clomiphene citrate- 1 mg/kg) and polyherbal tablets (Group IV - 500 mg/kg, Group V- 750 mg/kg, and Group VI - 1000 mg/kg) up to 50 days. Vaginal smears were taken daily to check the estrous cycle. Body weight was measured weekly. Blood samples were withdrawn on 0,21 and 50 days for the determination of fasting blood glucose, lipid profile, LH, FSH, and hormonal levels. Results: Administration of letrozole caused the abnormality in serum sex hormone profile, lipid profile, glucose, and the estrous cycle. The treatment with polyherbal formulation significantly decreased (P < 0.0001) the level of testosterone and improved estradiol and progesterone levels (P < 0.0001). There was a decrease in elevated glucose levels from 71.51 ± 0.15 mg/dl in disease induced group to 57.33 ± 1.90 mg/dl in treatment groups. The triglycerides level was normalized to 33.41 ± 1.81 mg/dl and HDL level was increased to 40.63 ± 1.35 mg/dl in treatment groups. The polyherbal formulation by exerting its beneficial effect also caused the disappearance of the cysts in the ovaries. Conclusion: The polyherbal formulation was found to be effective in PCOS. The effect may be attributed to the individual herbs reported having a significant effect on the pathophysiology of letrozole induced PCOS.

Versatile Synthetic Platform for 1,2,3-Triazole Chemistry.

1,2,3-Triazole scaffolds are not obtained in nature, but they are still intensely investigated by synthetic chemists in various fields due to their excellent properties and green synthetic routes. This review will provide a library of all synthetic routes used in the past 21 years to synthesize 1,2,3-triazoles and their derivatives using various metal catalysts (such as Cu, Ni, Ru, Ir, Rh, Pd, Au, Ag, Zn, and Sm), organocatalysts, metal-free as well as solvent- and catalyst-free neat syntheses, along with their mechanistic cycles, recyclability studies, solvent systems, and reaction condition effects on regioselectivity. Constant developments indicate that 1,2,3-triazoles will help lead to future organic synthesis and are useful for creating molecular libraries of various functionalized 1,2,3-triazoles.

Microdentistry with Lasers.

Treating infants and young children is a rewarding experience, especially when we guide parents and children down the path of prevention and interception of oral disease. The pediatric dentist has to be updated about the new technologies to treating patients along with basic principles. This article gives a brief discussion on the types, applications, advantages, and limitations of the use of lasers in pediatric dentistry.

Dental Erosion and its Associated Factors In 11-16-Year Old School Children.

UNLABELLED: Dental erosion currently stands as a great challenge for the clinician, regarding the diagnosis, identification of the etiological factors, prevention and execution of an adequate treatment. AIMS: To evaluate the prevalence, severity, and associated factors on dental erosion in 11-16-years old. STUDY DESIGN: A cross sectional study was conducted among 2000 school children who were randomly selected. A questionnaire was given to the children that included personal demographic details and habit of consuming acidic foods and drinks. An index specific for dental erosion given by O Sullivan was used to assess every affected tooth. The values were subjected to chi-square test and multivariate logistic regression analysis. RESULTS: The prevalence of dental erosion was found to be 1.4%. Females (1.6%) were slightly more affected than males (1.3%). Public school children (2.1%) were found to be affected a little more than private children (0.7%). Chi square test showed significant association between type of school and erosion prevalence (p = 0.015). Most commonly affected teeth were lateral incisor (59.72%). CONCLUSION: The prevalence of dental erosion was found to be low when compared to various studies done all over the world.