In an attempt to find novel α-glucosidase inhibitors, an efficient, straightforward reaction to synthesize a library of fully substituted 6-amino-pyrazolo1,5-apyrimidines 3 has been investigated. ...Heating a mixture of α-azidochalcones 1 and 3-aminopyrazoles 2 under the mild condition afforded desired compounds with a large substrate scope in good to excellent yields. All obtained products were evaluated as α-glucosidase inhibitors and exhibited excellent potency with IC
values ranging from 15.2 ± 0.4 µM to 201.3 ± 4.2 µM. Among them, compound 3d was around 50-fold more potent than acarbose (IC
= 750.0 ± 1.5 µM) as standard inhibitor. Regarding product structures, kinetic study and molecular docking were carried out for two of the most potent ones.
A new series of imidazo1,2-bpyrazole derivatives
4a–o
was designed, synthesized, and screened for in vitro α-glucosidase inhibitory activity. All compounds showed high inhibitory activity in the ...range of IC
50
= 95.0 ± 0.5–372.8 ± 1.0 µM as compared to standard drug acarbose (IC
50
= 750 ± 1.5 µM) and were also found to be non-cytotoxic. Among the synthesized compounds, the most potent compound was compound
4j
with eightfold higher inhibitory activity compared to acarbose. Like acarbose, compound
4j
inhibited α-glucosidase in a competitive mode. Molecular modeling studies of the most potent compounds
4j
,
4f
,
4o
, and
4c
were also conducted.
Graphical abstract
Background
X‐linked mental retardation‐hypotonic facies syndrome‐1 (MRXFH1), caused by a mutation in the ATRX gene, is a rare syndromic form of X‐linked mental retardation (XLMR) that is mainly ...characterized by severe intellectual disability, dysmorphic facies, and skewed X‐inactivation pattern in carrier women.
Method
In this study, due to the genetic heterogeneity of the disease, we performed exome sequencing (ES) on a 15‐year‐old boy with primary microcephaly and intellectual disability. Also, Sanger sequencing, cosegregation analysis, and structural modeling were done to identify and verify the causative variant in the proband and other affected individuals in the family. In addition, we collected data from previously reported cases to compare with our patients' phenotypes.
Results
ES revealed a previously reported missense variant in the ATRX gene (c.5182G > C, p.Ala1728Pro), segregating with the new clinical characteristic including primary microcephaly in the pedigree. This variant meets the criteria of being likely pathogenic based on the ACMG variant interpretation guideline.
Conclusions
The findings of this study extend the spectrum of phenotypes associated with the identified variant and provide further details on its clinical features.
In this study, we identified novel clinical characteristics associated with the c.5182G>C variant in the ATRX gene by exome sequencing related to the X‐linked mental retardation‐hypotonic facies syndrom. In addition to a complete phenotypic description, we have performed bioinformatics evaluation related to the identified variant and have gone through protein modeling. Also, we carried out a literature review of the clinical characteristics of previously reported cases with mutations inthe helicase/ATPbinding domain.
A new series of 6-amino-pyrido2,3-dpyrimidine-2,4-dione derivatives 3a–3s were prepared via a facile and efficient reaction from α-azidochalcones and 6-amiouracils. The reactions were performed under ...mild conditions to produce the corresponding compounds in good to excellent yields. Obtained derivatives 3a–3s were evaluated for α-glucosidase inhibitory activity and all of them exhibited excellent in vitro yeast α-glucosidase inhibition with IC50 values ranging from 78.0 ± 2.0 to 252.4 ± 1.0 μM. For example, the most active compound 3o was around 10-fold more potent than acarbose, a standard drug (IC50 = 750.0 ± 1.5 μM). Kinetic study of compound 3o revealed that it inhibited α-glucosidase in a competitive mode. Molecular modeling studies of the most active compounds 3o, 3i, 3e and 3m were also performed.
A novel series of 6-amino-pyrido2,3-dpyrimidine-2,4-dione derivatives 3a–s were synthesized and evaluated as new inhibitors for α-glucosidase. All synthesized compounds were superior to standard drug (acarbose). Particularly, compound 3o was around 10-fold more potent than standard drug. The kinetic analysis of the compound 3o revealed that this compound inhibited α-glucosidase in a competitive manner (Ki = 69.2 μM). Docking studies of the most active compounds 3o, 3i, 3e, and 3m were also performed. Display omitted
•New series of 6-amino-pyrido2,3-dpyrimidines as α-glucosidase inhibitors.•The most active one 3o (IC50 = 78.0 ± 2.0µM), 10-fold more potent than the standard drug acarbose.•The kinetic analysis of 3o revealed its activity in a competitive manner (Ki = 69.2 µM).
Purpose: The growing attention and interest in alternatives for chemical preservatives with natural types has led to numerous studies on essential oils and plant extracts. Strawberries, due to their ...high respiration and metabolic activity, and high water content, are highly sensitive to microbial contamination. Research Method: An experiment was conducted to investigate the effect of the essential oils of some medicinal plants on the fungus Aspergillus sp. in strawberry fruit in in vivo and in vitro conditions as a factorial form in a completely randomized design with three replications. The first factor included the type of essential oil: frankincense, ginger, cinnamon, and tarragon essential oils, and the second factor included the concentration of essential oil at five levels (0, 200, 400, 600, and 800 µL.L-1). Findings: In vitro results showed that with the increase in the concentration of plant essential oils, their antifungal activity increases. As a result, the lowest fungus colony diameter was obtained from the concentration of 800 µL.L-1 of essential oil. A comparison of the average type of essential oil showed that cinnamon essential oil had more antifungal activity than other essential oils used, so that at any level (200 to 800 µL.L-1), it caused a 100% inhibition of Aspergillus sp. growth. In vivo, results showed that the best appearance of the fruit and the highest soluble solids were recorded from the concentration of 800 µL.L-1 of essential oil. Cinnamon essential oil treatment resulted in the best fruit appearance, the highest soluble solids, and the highest levels of antioxidants, anthocyanin, and sugar compared to frankincense essential oil. Research limitations: There were no limitations. Originality/Value: Among the essential oils, cinnamon essential oil showed better antifungal activity against Aspergillus sp., which causes strawberry fruit spoilage. Therefore, it can be used as a substitute for chemical fungicides, although other essential oils may also be effective.
Objectives: This study investigates the impact of neurofeedback on perceptual-motor skills of5 to 12 years old children with Attention Deficit Hyperactive Disorder (ADHD). Methods: In this clinical ...study, 40 children between the ages of 5-12 years, who were patientsof the Tavanesh Clinic and diagnosed with ADHD, were randomly chosen and divided intotwo groups of control and test. 20-neurofeedback intervention sessions were performed.The tools utilized in this study included Bruninks-Oseretsky Test of Motor Proficiency andChild behavior checklist (CBCL) survey questionnaire. For evaluation after the intervention,Bruninks-Oseretsky Test of Motor Proficiency scale for children, along with CBCLquestionnaire surveys were asked to fill up by the participants' mothers. Results: After the intervention, the analysis of the scores in all perceptual-motor skills showedsignificant differences in both groups, but no significant difference was observed in the subtestof strength. The CBCL survey questionnaire revealed that the average scores on attentiondisorder, aggression, lack of attention and hyperactivity, externalizing and general problems inthe test group is significantly less than that of the control group. However, in the confrontationalbehavior (internalization), there was no statistically significant difference between the test andcontrol groups. There was a correlation between the change of motor skills and change ofbehavioral patterns in ADHD children. Discussion: Neurofeedback intervention can have positive effects on improving the perceptualmotorskills of children with ADHD.
Purpose: The main objective of this work was to assess the effectiveness of potassium permanganate (KMno4), 1-methylcyclopropene (1-MCP) and different packaging on reducing the occurrence of decay ...and extending apricot fruit shelf life during cold storage. Research Method: Fruits were harvested manually from a commercial apricot orchard based on peel color (light-green) and total soluble solids approximately 10.5 °Brix. Fruits were then dipped in KMnO4 (20 or 50 ppm) solution for 3 minutes or exposed to 1-MCP (0 or 1 µL L-1) for 20 h at 20 °C. Thereafter, fruits were placed into polyethylene trays and covered with cellophane films or polyethylene lid (packed with its lid) to create a passive modified atmosphere packaging, whilst the control group remained unpacked and then stored at 0.5 ± 0.5 °C with 80% RH. Findings: The results showed that weight loss significantly reduced when apricot fruit covered with cellophane (10.02%) or when packed in PE containers (0.86%) compared to the unpacked control (37.61%), consequently, the firmness value was higher in unwrapped than wrapped fruit due to the high dehydration of unpacked fruit. Application of KMnO4 or 1-MCP had no significant effect on TSS. Interestingly, the shelf life extended 3-fold greater in treated fruit with KMnO4 at 20 ppm or 1-MCP (1 µL L-1) when packed in PE container compared to control unwrapped fruit. Research limitations: No limitation to report. Originality/Value: In general, KMnO4 or 1-MCP treatments had a positive effect on fruit color and taste in packed samples on cellophane or PE container.
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