Explore the vast range of titles available.

In this study, 5-amino-nicotinic acid derivatives (1–13) have been designed and synthesized to evaluate their inhibitory potential against α-amylase and α-glucosidase enzymes. The synthesized compounds (1–13) exhibited promising α-amylase and α-glucosidase activities. IC50 values for α-amylase activity ranged between 12.17 ± 0.14 to 37.33 ± 0.02 µg/mL ± SEM while for α-glucosidase activity the IC50 values were ranged between 12.01 ± 0.09 to 38.01 ± 0.12 µg/mL ± SEM. In particular, compounds 2 and 4–8 demonstrated significant inhibitory activities against α-amylase and α-glucosidase and the inhibitory potential of these compounds was comparable to the standard acarbose (10.98 ± 0.03 and 10.79 ± 0.17 µg/mL ± SEM, respectively). In addition, the impact of substituent on the inhibitory potential of these compounds was assessed to establish structure activity relationships. Studies in molecular simulations were conducted to better comprehend the binding properties of the compounds. All the synthesized compounds were extensively characterized with modern spectroscopic methods including 1H-NMR, 13C–NMR, FTIR, HR-MS and elemental analysis.

Background Inflammation is known to involve in many pathological processes of different diseases, but the current therapy causes adverse effects. Thus, there is a great interest for the discovery of flavonoids as a valuable alternative to classical analgesic and anti-inflammatory agent with dual-inhibitory action, especially on both COX-2 and 5-LOX which can minimize or overcome this problem. Results In the present work, drug-likeness properties of the synthesized flavonoids via Lipinski’s Rule of Five were predicted using QikProp prior to evaluation of their COX and LOX inhibitory activities using enzyme assays. Subsequently, molecular docking was performed using GLIDE to analyse their binding behaviour. The results showed that all compounds obeyed the Lipinski’s Rule of Five. NPC6 and NPC7 had displayed better selectivity towards COX-2 as compared to Indomethacin with less than 50% inhibition against COX-1. In addition, these compounds also inhibited activity of 5-LOX. Their selectivity to COX-2 was due to the binding to hydrophobic region and extends to lobby region near the entrance of COX binding site forming hydrogen bond with Ser530. Interestingly, these compounds showed a similar binding mode as Zileuton in the active site of 5-LOX and formed hydrogen bond interaction with Ala424. Conclusion NPC6 and NPC7 had potential as dual inhibitor of COX-2 and 5-LOX. The scaffolds of these chemical entities are useful to be as lead compounds for the dual inhibition of COX-2 and 5-LOX.

The maturation of brain microvascular endothelial cells leads to the formation of a tightly sealed monolayer, known as the blood–brain barrier (BBB). The BBB damage is associated with the pathogenesis of age-related neurodegenerative diseases including vascular cognitive impairment and Alzheimer’s disease. Growing knowledge in the field of epigenetics can enhance the understanding of molecular profile of the BBB and has great potential for the development of novel therapeutic strategies or targets to repair a disrupted BBB. Histone deacetylases (HDACs) inhibitors are epigenetic regulators that can induce acetylation of histones and induce open chromatin conformation, promoting gene expression by enhancing the binding of DNA with transcription factors. We investigated how HDAC inhibition influences the barrier integrity using immortalized human endothelial cells (HCMEC/D3) and the human induced pluripotent stem cell (iPSC)-derived brain vascular endothelial cells. The endothelial cells were treated with or without a novel compound named W2A-16. W2A-16 not only activates Wnt/β-catenin signaling but also functions as a class I HDAC inhibitor. We demonstrated that the administration with W2A-16 sustained barrier properties of the monolayer of endothelial cells, as evidenced by increased trans-endothelial electrical resistance (TEER). The BBB-related genes and protein expression were also increased compared with non-treated controls. Analysis of transcript profiles through RNA-sequencing in hCMEC/D3 cells indicated that W2A-16 potentially enhances BBB integrity by influencing genes associated with the regulation of the extracellular microenvironment. These findings collectively propose that the HDAC inhibition by W2A-16 plays a facilitating role in the formation of the BBB. Pharmacological approaches to inhibit HDAC may be a potential therapeutic strategy to boost and/or restore BBB integrity.

Heterocyclic pyrimidine nucleus, which is an essential base component of the genetic material of deoxyribonucleic acid, demonstrated various biological activities. A series of bis-pyrimidine Schiff bases were synthesized and screened for its antimicrobial and anticancer potentials. The molecular docking study was carried to find the interaction between active molecules with receptor. The structures of synthesized bis-pyrimidine Schiff bases were confirmed by spectral studies. The synthesized bis-pyrimidine derivatives were evaluated for their antimicrobial activity (MIC = µmol/mL) against selected Gram positive; Gram negative bacterial and fungal strains by tube dilution method. The anticancer activity (IC50 = µmol/mL) of the synthesized compounds was determined against human colorectal carcinoma (HCT116) cancer cell line by Sulforhodamine B (SRB) assay. Molecular docking studies provided information regarding the binding mode of active bis-pyrimidine Schiff bases with the cyclin-dependent kinase 8 (CDK8) receptor. The antimicrobial screening results indicated that compounds, q1 (MICbs = 0.83 µmol/mL), q16 (MICan = 1.54 µmol/mL and MICec = 0.77 µmol/mL), q1 and q19 (MICca = 0.41 µmol/mL) and q20 (MIC = 0.36 µmol/mL) are the most active ones. Compounds q1 (IC50 = 0.18 µmol/mL) have emerged as potent anticancer molecule against human colorectal carcinoma cancer cell line than the reference drug, 5-fluorouracil. Molecular docking studies indicated that compound q1 (the most active molecule) has the maximum hydrogen bond interaction (four) and π–π stacking (three) network among the bis-pyrimidine Schiff bases. [Figure not available: see fulltext. Caption: Graphical illustration of predicted binding mode of bis-pyrimidine Schiff bases in the active site of CDK8. a. Compound 1 (magenta color), b. Compound 5 (green color), c. Compound 8 (red color), d. Compound 13 (split pea color).]

BackgroundA series of 2-(1H-benzo[d]imidazol-2-ylthio)-N-(substituted 4-oxothiazolidin-3-yl) acetamides was synthesized and characterized by physicochemical and spectral means. The synthesized compounds were evaluated for their in vitro antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Candida albicans and Aspergillus niger by tube dilution method. The in vitro cytotoxicity study of the compounds was carried out against human colorectal (HCT116) cell line. The most promising anticancer derivatives (5l, 5k, 5i and 5p) were further docked to study their binding efficacy to the active site of the cyclin-dependent kinase-8.ResultsAll the compounds possessed significant antimicrobial activity with MIC in the range of 0.007 and 0.061 µM/ml. The cytotoxicity study revealed that almost all the derivatives were potent in inhibiting the growth of HCT116 cell line in comparison to the standard drug 5-fluorouracil. Compounds 5l and 5k (IC50 = 0.00005 and 0.00012 µM/ml, respectively) were highly cytotoxic towards HCT116 cell line in comparison to 5-fluorouracil (IC50 = 0.00615 µM/ml) taken as standard drug.ConclusionThe molecular docking studies of potent anticancer compounds 5l, 5k, 5i and 5p showed their putative binding mode and significant interactions with cyclin-dependent kinase-8 as prospective agents for treating colon cancer.

In this study we are going to present thiazole based carbohydrazide in search of potent antidiabetic agent as α-amylase inhibitors. Thiazole based carbohydrazide derivatives 1-25 have been synthesized, characterized by 1HNMR, 13CNMR, and EI-MS, and evaluated for α-amylase inhibition. Except compound 11 all analogs showed α-amylase inhibitory activity with IC50 values from 1.709 ± 0.12 to 3.049 ± 0.25 μM against the standard acarbose (IC50 = 1.637 ± 0.153 μM). Compounds 1, 10, 14, and 20 exhibited outstanding inhibitory potential with IC50 value 1.763 ± 0.03, 1.747 ± 0.20, 1.709 ± 0.12, and 1.948 ± 0.23 μM, respectively, compared with the standard acarbose. Structure activity relationships have been established for the active compounds. To get an idea about the binding interaction of the compounds, molecular docking studies were done.

We have synthesized new series of bisindole analogs (1–27), characterized by 1HNMR and HR-EI-MS and evaluated for their anti-leishmanial potential. All compounds showed outstanding inhibitory potential with IC50 values ranging from 0.7 ± 0.01 to 13.30 ± 0.50 µM respectively when compared with standard pentamidine with IC50 value of 7.20 ± 0.20 µM. All analogs showed greater potential than standard except 10, 19 and 23 when compared with standard. Structure activity relationship has been also established for all compounds. Molecular docking studies were carried out to understand the binding interaction of active molecules.

In this study we are going to present thiazole based carbohydrazide in search of potent antidiabetic agent as [alpha]-amylase inhibitors. Thiazole based carbohydrazide derivatives 1-25 have been synthesized, characterized by [sup.1]HNMR, [sup.13]CNMR, and EI-MS, and evaluated for [alpha]-amylase inhibition. Except compound 11 all analogs showed [alpha]-amylase inhibitory activity with [IC.sub.50] values from 1.709 [+ or -] 0.12 to 3.049 [+ or -] 0.25 [micro]M against the standard acarbose ([IC.sub.50] = 1.637 [+ or -] 0.153 [micro]M). Compounds 1, 10, 14, and 20 exhibited outstanding inhibitory potential with [IC.sub.50] value 1.763 [+ or -] 0.03, 1.747 [+ or -] 0.20, 1.709 [+ or -] 0.12, and 1.948 [+ or -] 0.23 [micro]M, respectively, compared with the standard acarbose. Structure activity relationships have been established for the active compounds. To get an idea about the binding interaction of the compounds, molecular docking studies were done.

Chitosan has become a highlighted polymer, gaining paramount importance and research attention. The fact that this valuable polymer can be extracted from food industry-generated shell waste gives it immense value. Chitosan, owing to its biological and physicochemical properties, has become an attractive option for biomedical applications. This review briefly runs through the various methods involved in the preparation of chitosan and chitosan nanoforms. For the first time, we consolidate the available scattered reports on the various attempts towards greens synthesis of chitosan, chitosan nanomaterials, and chitosan nanocomposites. The drug delivery applications of chitosan and its nanoforms have been reviewed. This review points to the lack of systematic research in the area of green synthesis of chitosan. Researchers have been concentrating more on recovering chitosan from marine shell waste through chemical and synthetic processes that generate toxic wastes, rather than working on eco-friendly green processes—this is projected in this review. This review draws the attention of researchers to turn to novel and innovative green processes. More so, there are scarce reports on the application of green synthesized chitosan nanoforms and nanocomposites towards drug delivery applications. This is another area that deserves research focus. These have been speculated and highlighted as future perspectives in this review.

Water is a necessity for all living and non-living organisms on this planet. It is understood that clean water sources are decreasing by the day, and the rapid rise of Industries and technology has led to an increase in the release of toxic effluents that are discharged into the environment. Wastewater released from Industries, agricultural waste, and municipalities must be treated before releasing into the environment as they contain harmful pollutants such as organic dyes, pharmaceuticals wastes, inorganic materials, and heavy metal ions. If not controlled, they can cause serious risks to human beings' health and contaminate our environment. Membrane filtration is a proven method for the filtration of various harmful chemicals and microbes from water. Carbon nanomaterials are applied in wastewater treatment due to their high surface area, making them efficient adsorbents. Carbon nanomaterials are being developed and utilized in membrane filtration for the treated wastewater before getting discharged with the rise of nanotechnology. This review studies carbon nanomaterials like fullerenes, graphenes, and CNTs incorporated in the membrane filtration to treat wastewater contaminants. We focus on these CNM based membranes and membrane technology, their properties and applications, and how they can enhance the commonly used membrane filtration performance by considering adsorption rate, selectivity, permeability, antimicrobial disinfectant properties, and compatibility with the environment.