A Series of Benzylidenes Linked to Hydrazine‐1‐carbothioamide as Tyrosinase Inhibitors: Synthesis,Biological Evaluation and Structure−Activity Relationship

Tyrosinase is a type 3 copper enzyme responsible for skin pigmentation disorders, skin cancer, and enzymatic browning of vegetables and fruits. In the present article, 12 small molecules of 2‐benzylidenehydrazine‐1‐carbothioamide were designed, synthesized and evaluated for their anti‐tyrosinase activities followed by molecular docking and pharmacophore‐based screening. Among synthesized thiosemicarbazone derivatives, one compound, (2E)‐2‐[(4‐nitrophenyl)methylidene]hydrazine‐1‐carbothioamide, is the strongest inhibitor of mushroom tyrosinase with IC₅₀ of 0.05 μM which demonstrated a 128‐fold increase in potency compared to the positive control. Kinetic studies also revealed mix type inhibition by this compound. Docking studies confirmed the complete fitting of the synthesized compounds into the tyrosinase active site. The results underline the potential of 2‐benzylidenehydrazine‐1‐carbothioamides as potent pharmacophore to extend the tyrosinase inhibition in drug discovery.     

Increasing the quality of services and resource utilization in vehicular cloud computing using best host selection methods

One of the technology for increasing the safety and welfare of humans in roads is Vehicular Cloud Computing (VCC). This technology can utilize cloud computing advantages in the Vehicular Ad Hoc Network (VANET). VCC by utilizing modern equipment along with current vehicles, can play a significant role in the area of smart transportation systems. Given the potential of this technology, effective methods for managing existing resources and providing the expected service quality that is essential for such an environment are not yet available as it should. One of the most important barriers to providing such solutions seems to be resource constraints and very high dynamics in vehicles in VCC. In this article, based on virtualization and taking into account the environment with these features, we propose simple ways to manage resources better and improve the quality of service. We were able to achieve better results in simulation than previous methods by providing a flexible data structure to control the important data in the environment effectively. To illustrate the impact of the proposed methods, we compared them with some of the most important methods in this context, and we used SUMO 1.2.0 and MATLAB R2019a software to simulate them. Simulation results indicate that the proposed methods provide better results than previous methods in terms of resource efficiency, Quality of Service (QoS), and load balancing.

     

Investigation of Hydrogen Glow Discharge Cleaning Side Effects on Tungsten

Plasma Physics Reports - Hydrogen glow discharge cleaning (H-GDC) is a routine conditioning procedure for the modern tokamaks and the future fusion machines, including ITER. Due to the low energy...     

Design and Synthesis of Selective Acetylcholinesterase Inhibitors: Arylisoxazole‐Phenylpiperazine Derivatives

In this work, a novel series of arylisoxazole‐phenylpiperazines were designed, synthesized, and evaluated toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Our results revealed that [5‐(2‐chlorophenyl)‐1,2‐oxazol‐3‐yl](4‐phenylpiperazin‐1‐yl)methanone ( 5c ) was the most potent AChE inhibitor with IC₅₀ of 21.85 μm . It should be noted that most of synthesized compounds showed no BChE inhibitory activity and [5‐(2‐fluorophenyl)‐1,2‐oxazol‐3‐yl](4‐phenylpiperazin‐1‐yl)methanone ( 5a ) was the most active anti‐BChE derivative (IC₅₀=51.66 μm ). Also, kinetic studies for the AChE and BChE inhibitory activity of compounds 5c and 5a confirmed that they have simultaneously bound to the catalytic site (CS) and peripheral anionic site (PAS) of both AChE and BChE. Furthermore, docking study of compound 5c showed desired interactions of that compound with amino acid residues located in the active and peripheral anionic sites. Compound 5c was also evaluated for its BACE1 inhibitory activity and demonstrated IC₅₀=76.78 μm . Finally, neuroprotectivity of compound 5c on Aβ‐treated neurotoxicity in PC12 cells depicted low activity.     

Antimicrobial activities of Asafoetida and Shirazi thyme essential oils improve the vase life of gerbera cut flowers

This study was conducted to evaluate the chemical composition of asafoetida (Ferula assa-foetida) essential oil (FAEO) and Shirazi thyme (Zataria multiflora) EO (ZMEO) and their impact on vase life of gerbera cut flowers (Gerbera jamesonii cv. Rosalyn). Five concentrations of both, ZMEO and FAEO including 0, 100, 200, 300 and 400 mg L^?1 used as continuous vase solution for gerbera cut flowers. EOs used in this study were extracted by hydrodistillation method using Clevenger apparatus. They were analyzed by GC and GC–MS for determination of the active compounds. Thirty five compounds were identified in ZMEO, mainly including thymol (40.1%), p-cymene (15.5%) and carvacrol (6.5%). Also, thirty compounds were identified in FAEO. The main components were trans propenyl sec-butyl disulfide (21.7%), eudesmol (10-epu-γ) (19.2%) and cis propenyl sec-butyl disulfide (10.2%). The results showed that both ZMEO and FAEO at all concentrations could act as an effective antibacterial compounds and this property increased by increasing their concentration. The results of this research showed that ZMEO increased the vase life at all concentrations but high concentrations of FAEO increased mortality percentage and reduced the vase life of cut flowers. The relative fresh weight and vase solution uptake of gerbera cut flowers increased by the applied EOs treatments. ZMEO at 400 mg L^? 1 and FAEO at 300 and 400 mg L^? 1 resulted the least stem color change. Overall, 200 mg L^? 1 ZMEO and 100 mg L^? 1 FAEO were the best treatments for maintenance of gerbera cut flowers quality during vase life.     

Ugi Bis-Amide Derivatives as Tyrosinase Inhibitor; Synthesis,Biology Assessment,and in Silico Analysis

Herein, a straightforward synthetic strategy mediated by Ugi reaction was developed to synthesize novel series of compounds as tyrosinase inhibitors. The structures of all compounds were confirmed by FT-IR, ¹H-NMR, ¹³C-NMR, and CHNOS techniques. The tyrosinase inhibitory activities of all synthesized derivatives 5a – m were determined against mushroom tyrosinase and it was found that derivative 5c possesses the best inhibition with an IC₅₀ value of 69.53±0.042 μM compared to the rest of the synthesized derivatives. Structure–activity relationships (SARs) showed that the presence of 4-MeO or 4-NO₂ at the R² position plays a key role in tyrosinase inhibitory activities. The enzyme kinetics studies showed that compound 5c is an noncompetitive inhibitor. For in silico study, the allosteric site detection was first applied to find the appropriate binding site and then molecular docking and molecular dynamic studies were performed to reveal the position and interactions of 5c as the most potent inhibitor within the tyrosinase active site. The results showed that 5c bind well with the proposed binding site and formed a stable complex with the target protein.