As part of our effort to identify potent α‐amylase inhibitors, in the present study, a novel series of fluorinated thiazolidinone‐pyrazole hybrid molecules were prepared by the condensation of ...3‐(aryl/benzyloxyaryl)‐pyrazole‐4‐carbaldehydes with fluorinated 2,3‐disubstituted thiazolidin‐4‐ones. The structures of the newly synthesized compounds were confirmed by infrared, 1H nuclear magnetic resonance (NMR), 13C NMR, and liquid chromatography–mass spectrometry data. All the compounds were screened for their α‐amylase inhibitory and free radical scavenging activities by DPPH (1,1‐diphenyl‐2‐picrylhydrazyl) and ABTS methods. Among the tested compounds, compound 8g emerged as a promising α‐amylase inhibitor with IC50 = 0.76 ± 1.23 µM, and it was found to be more potent than the standard drug acarbose (IC50 = 0.86 ± 0.81 μM). Compounds 8b and 8g showed strong free radical scavenging activity compared to the standard butylated hydroxyl anisole. The kinetic study of compound 8g revealed the reversible, classical competitive inhibition mode on the α‐amylase enzyme. Molecular docking and dynamic simulations studies were performed for the most potent compound 8g, which displayed remarkable hydrogen bonding with the α‐amylase protein (PDB ID: 1DHK).
Novel fluorinated thiazolidinone‐pyrazole hybrid molecules were prepared and tested as α‐amylase inhibitors and free radical‐scavenging agents. Compound 8g emerged as a promising α‐amylase inhibitor that was more potent than the standard drug acarbose. Compounds 8b and 8g showed strong free radical‐scavenging activity. Molecular docking revealed remarkable hydrogen bonding of compound 8g with the α‐amylase protein.
MRSA infection is one of the alarming diseases in the current scenario. Identifying newer molecules to treat MRSA infection is of urgent need. In the present study, we have designed fluorinated ...thiazolidinone derivatives with various aryl/heteroaryl units at 5th position of the thiazolidinone core as promising anti‐MRSA agents. All the compounds were screened for antibacterial activity against four bacterial strains. Among the tested compounds, the halogenated compounds with simple arylidene ring, (5Z)‐5‐(3‐chloro‐2‐fluorophenyl)methylidene‐2‐(1,3‐thiazol‐2‐yl)amino‐1,3‐thiazol‐4(5H)‐one (4b), (5Z)‐5‐(4‐chloro‐2‐fluorophenyl)methylidene‐2‐(1,3‐thiazol‐2‐yl)amino‐1,3‐thiazol‐4(5H)‐one (4c), (5Z)‐5‐(3‐fluoro‐4‐methylphenyl)methylidene‐2‐(1,3‐thiazol‐2‐yl)amino‐1,3‐thiazol‐4(5H)‐one (4f) and (5Z)‐5‐(3,5‐difluorophenyl)methylidene‐2‐(1,3‐thiazol‐2‐yl)amino‐1,3‐thiazol‐4(5H)‐one (4g) showed excellent activity with MIC 3.125–6.25 μg/mL against S. aureus and P. aeruginosa organism. Furthermore, these potent compounds were screened against MRSA strains, ESKAPE panel organism, and H37Rv mycobacterium strain. Compounds 4c (MIC 0.39 μg/mL), and 4f (MIC 0.39 and 0.79 μg/mL) displayed promising activity against MRSA strains (ATCC and clinical isolates, respectively). The most potent compounds, 4c and 4f eradicated the growth of bacterial colonies in a time‐kill assay indicated that these are bactericidal in nature. The preliminary toxicity study of the potent molecules revealed that these compounds are non‐hemolytic in nature as they did not induce lysis in human RBCs. In addition, the molecular docking and dynamics studies of compounds 4b, 4c, 4f and 4g were carried out on MurB protein of S. aureus (PDB code: 1HSK). Docking results demonstrated remarkable hydrogen bonding interaction with key amino acids ARG310, ASN83, GLY79 and π‐π interactions with TYR149 which confirm the mode of action of the molecules.
A series of bis-phenoxyacetic acids
2 were prepared starting from corresponding unsubstituted/substituted 1,4-quinols
1. The fusion of bis-phenoxyacetic acids
2 with thiocarbohydrazide gave the ...corresponding bis-4-amino-5-mercapto-1,2,4-triazol-3-yl-methyleneoxyphenylenes (
3) in a one pot reaction. The reaction of bis-triazoles
3 with various reagents afforded
N-bridged heterocycles
4–
6 in good yields. The newly synthesised compounds were screened for their anticancer activity against a panel of 60 cell lines derived from seven cancer types namely, lung, colon, melanoma, renal, ovarian, CNS and leukemia. Some of the tested compounds showed promising anticancer properties.
Background
Melasma is a chronic recalcitrant pigmentary disorder whose treatment frustrates physician and patient alike. Tranexamic acid, a plasmin inhibitor, has demonstrated hypopigmenting ...properties.
Aim
To compare safety and efficacy of combination of oral tranexamic acid (TXA) and topical fluocinolone‐based combination cream (FbTC) with that of topical FbTC alone in melasma.
Method
One hundred and eighty patients patients of facial melasma of either sex attending dermatology OPD were screened. Consenting 130 participants were randomized into two blinded groups with 65 patients in each group. Group A patients received oral tranexamic acid 250 mg and oral ranitidine 150 mg twice daily and applied a triple combination cream containing fluocinolone acetonide 0.01%, tretinoin 0.05% and hydroquinone 2% once daily, and Group B was asked to take placebo tablets (calcium lactate and multivitamin) and apply the cream only for 12 weeks. Response was evaluated using modified melasma area severity index (mMASI) and graded mMASI improvement at 4th, 8th and 12th weeks, and at 24th week for recurrence. Data were analysed using SPSS software.
Results
Results were analysed in 120 patients who completed the study with 61 and 59 patients in group A and B, respectively. Demographic profile was equally distributed in both the groups. In group A, 13.1% patients showed marked improvement (>75%) in mMASI as compared to group B (1.7%) at 4th week. By 12th week, 65.6% patients had marked improvement in group A in contrast to only 27.1% in group B. At 24th week, group A (65.6%) had sustained improvement as compared to group B (11.9%) despite stopping treatment; all of which were statistically significant. Recurrence observed was 18.03% in group A vs. 64.4% in group B at 24th week.
Conclusion
Oral tranexamic acid is definitely a boon to the armamentarium of melasma management and should be used as an adjuvant to fluocinolone‐based triple combination cream for a faster, sustained improvement and to prevent recurrence.
MicroRNAs as cancer biomarkers in serum, plasma, and other body fluids are often used but analysis of miRNA in urine is limited. We investigated the expression of selected miRNAs in the paired urine, ...serum, cervical scrape, and tumor tissue specimens from the women with cervical precancer and cancer with a view to identify if urine miRNAs could be used as reliable non-invasive biomarkers for an early diagnosis and prognosis of cervical cancer. Expression of three oncomiRs (miR-21, miR-199a, and miR-155-5p) and three tumor suppressors (miR-34a, miR-145, and miR-218) as selected by database search in cervical pre-cancer, cancer, and normal controls including cervical cancer cell lines were analyzed using qRT-PCR. The expression of miRNAs was correlated with various clinicopathological parameters, including HPV infection and survival outcome. We observed a significant overexpression of the oncomiRs and the downregulation of tumor suppressor miRNAs. A combination of miR-145-5p, miR-218-5p, and miR-34a-5p in urine yielded 100% sensitivity and 92.8% specificity in distinguishing precancer and cancer patients from healthy controls and it well correlates with those of serum and tumor tissues. The expression of miR-34a-5p and miR-218-5p were found to be independent prognostic factors for the overall survival of cervical cancer patients. We conclude that the evaluation of the above specific miRNA expression in non-invasive urine samples may serve as a reliable biomarker for early detection and prognosis of cervical cancer.
Gallbladder cancer (GBC) is an aggressive gastrointestinal malignancy with no approved targeted therapy. Here, we analyze exomes (n = 160), transcriptomes (n = 115), and low pass whole genomes (n = ...146) from 167 gallbladder cancers (GBCs) from patients in Korea, India and Chile. In addition, we also sequence samples from 39 GBC high-risk patients and detect evidence of early cancer-related genomic lesions. Among the several significantly mutated genes not previously linked to GBC are ETS domain genes ELF3 and EHF, CTNNB1, APC, NSD1, KAT8, STK11 and NFE2L2. A majority of ELF3 alterations are frame-shift mutations that result in several cancer-specific neoantigens that activate T-cells indicating that they are cancer vaccine candidates. In addition, we identify recurrent alterations in KEAP1/NFE2L2 and WNT pathway in GBC. Taken together, these define multiple targetable therapeutic interventions opportunities for GBC treatment and management.
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•Preparation of Xylan/Chitosan/Montmorillonite porous scaffold by freeze drying.•Increase in pore size of scaffold on increasing MMT content up to 4%.•Ca/P ratio of 1.67 in SBF ...deposited apatite was achieved at 2% MMT concentration.•Needle like apatite morphology was observed in SBF at 5% MMT concentration.•Scaffolds possessed cell attachment tendency.
The present study reports the fabrication of Xylan/Chitosan/Montmorillonite (MMT) composite scaffold by freeze drying process with the aim of achieving improved properties for bone tissue engineering applications. The scaffolds were characterized using Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), Scanning electron microscopy (SEM) and mechanical testing. The fabricated scaffolds were found to be highly porous with variations in pore size (102 μm–290 μm) on varying the filler concentration. XRD study revealed complete exfoliation of MMT incorporated in polymer conjugates (Xylan/Chitosan) prepared by Maillard reaction. In-vitro bio-mineralization study revealed significant apatite deposition on polymer matrix. Scaffolds with 5% MMT concentration exhibited needle like morphology of deposited apatite which can further provide synergistic response in increasing the mechanical properties of scaffolds when placed in contact with body fluid. The average length and thickness of apatite needles were calculated to be 140 μm and 1.2 μm respectively. The deposited apatite crystals on scaffold with 2% MMT content demonstrated Ca/P ratio of 1.67, resembling that of natural bone apatite. Swelling and biodegradation behavior of scaffold were also studied with regard to hydrophilic and barrier effect of MMT on composites. MTT assay revealed non-cytotoxic nature of scaffold with good cell viability.
Proteins are important macronutrients for the human body to grow and function throughout life. Although proteins are found in most foods, their very dissimilar digestibility must be taking into ...consideration when addressing the nutritional composition of a diet. This review presents a comprehensive summary of the in vitro digestibility of proteins from plants, milk, muscle, and egg. It is evident from this work that protein digestibility greatly varies among foods, this variability being dependent not only upon the protein source, but also the food matrix and the molecular interactions between proteins and other food components (food formulation), as well as the conditions during food processing and storage. Different approaches have been applied to assess in vitro protein digestibility (IVPD), varying in both the enzyme assay and quantification method used. In general, animal proteins tend to show higher IVPD. Harsh technological treatments tend to reduce IVPD, except for plant proteins, in which thermal degradation of anti-nutritional compounds results in improved IVPD. However, in order to improve the current knowledge about protein digestibility there is a vital need for understanding dependency on a protein source, molecular interaction, processing and formulation and relationships between. Such knowledge can be used to develop new food products with enhanced protein bioaccessibility.
Background & objectives: Sahariya, a primitive tribe of Central India, has shown significantly increased incidence of pulmonary tuberculosis (PTB). Our previous study on Sahariya showed a significant ...association of −403G>A single nucleotide polymorphism (SNP) of CCL5 with susceptibility to PTB. Hence, this study was aimed to analyze a genotype-phenotype relationship of this disease-associated SNP to develop a potential diagnostic marker for TB in this tribe.
Methods: The present study was carried out on 70 plasma samples from Sahariya tribe, wherein the plasma CCL5 level was determined using a commercially available ELISA kit.
Results: The level of CCL5 decreased significantly in patients who were on therapy/completed their therapy inactive TB patient/inactive PTB (IPTB), particularly with AA genotype of −403G>A (P=0.046). The level, with AA genotype, was also found to gradually decrease in sputum 3+ and 1+/2+ than in sputum-negative samples. Similarly, the CCL5 level was found to be higher in sputum-positive/active TB patients than in IPTB group and healthy controls.
Interpretation & conclusions: Our results suggested that the CCL5 level was influenced collectively not only by the genotypes of −403G>A SNP and bacillary load but also by the treatment. Thus, CCL5 may be considered for the development of a diagnostic marker and also as an indicator of recovery.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The design, synthesis, and biological screening of novel 4-aryl-6-6-(2,4-dichlorophenyl)-2-methylpyridin-3-yl-3,4-dihydropyrimidine-2(1
H
)-thiones and ...2′-amino-6′-aryl-6-(2,4-dichlorophenyl)-2-methyl3,4′-bipyridine-3′-carbonitriles are described. The reaction involves Claisen–Schmidt condensation to afford the target compounds in up to 93% yield. The synthesized compounds were characterized by using FT-IR,
1
H NMR,
13
C NMR, mass spectrometry, and elemental analysis and were screened for their antibacterial activity against both gram-negative and gram-positive bacterial strains. Methoxy-, hydroxy-, and halogen-substituted derivatives showed good inhibitory effect against the tested microorganisms. Also, some of the compounds showed better anti-inflammatory activity when compared to the standards. The electron-donor properties of the novel pyrimidine derivatives were confirmed by quantum chemical studies.
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