Gold nanoparticles (GNPs) have been proposed as carriers for drugs to improve their intrinsic therapeutic activities and to overcome pharmacokinetic problems. In this study, novel nanosystems constituted by a model β-diketo acid (DKA) grafted to the surface of GNPs were designed and synthesized following the "multivalent highaffinity" binding strategy. These first nanoscale DKA prototypes showed improved inhibition of HIV-1 integrase (HIV-1 IN) catalytic activities as compared with free DKA ligands.
The present synthetic strategy involves the synthesis of indolyl-triazolo-thiadiazole heterocyclic ring systems 8–13 from the condensation of 4-amino-5-(1H-indol-2-yl)-3H-1,2,4-triazole-3-thione 1 with the aromatic carboxylic acid derivatives 2–7 in presence of POCl3 for 1 h. All compounds were obtained in very good yields and have been well-characterized using spectroscopic techniques. Exclusively, good quality crystals from the target organic hybrid 8-(1H-indol-2-yl)-5-(p-tolyl)-[1,2,4]triazolo [3,4-b][1,3,4]thiadiazole 9 were obtained and found suitable for X-ray single crystal diffraction measurement, which is used to confirm and analyze the molecular and supramolecular structure aspects of 9. The solid-state structure of the synthesized molecule 9 agrees very well with other characterizations. The packing of 9 is dominated by the N…H, S…H, C…C and S…C non-covalent interactions, which agree with the Hirshfeld surface analysis. The percentages of these contacts are calculated to be 20.3%, 5.4%, 9.4% and 4.3%, respectively.
Cancer is the most severe disease worldwide. Every year, tens of millions of people are diagnosed with cancer, and over half of those people will ultimately die from the disease. Hence, the discovery of new inhibitors for fighting cancer is necessary. As a result, new indolyl-triazole hybrids were synthesized to target breast and liver cancer cells. The synthetic strategy involves glycosylation of the 4-aryltriazolethiones 3a−b with acetylprotected α-halosugars in the presence of K 2 CO 3 in acetone to give a mixture of β-S-glycosides 6a−b, 7a−b, and β-N-glycosides 8a−b, 9a−b. Chemo-selective S-glycosylation was achieved using NaHCO 3 in ethanol. The migration of glycosyl moiety from sulfur to nitrogen (S → N glycosylmigration) was achieved thermally without any catalyst. Alkylation of the triazole-thiones with 2bromoethanol and 1-bromopropan-2-ol in the presence of K 2 CO 3 yielded the corresponding S-alkylated products. The synthesized compounds were tested for their cytotoxicity using an MTT assay and for apoptosis induction targeting PARP-1 and EGFR. Compounds 12b, 13a, and 13b exhibited cytotoxic activities with promising IC 50 values of 2.67, 6.21, 1.07 μM against MCF-7 cells and 3.21, 8.91, 0.32 μM against HepG2 cells compared to Erlotinib (IC 50 = 2.51, 2.91 μM, respectively) as reference drug. Interestingly, compounds 13b induced apoptosis in MCf-7 and HepG2 cells, arresting the cell cycle at the G2/M and S phases, respectively. Additionally, the dual enzyme inhibition seen in compound 13b against EGFR and PARP-1 is encouraging, with IC 50 values of 62.4 nM compared to Erlotinib (80 nM) and 1.24 nM compared to Olaparib (1.49 nM), respectively. The anticancer activity was finally validated using an in vivo SEC-cancer model; compound 13b improved both hematological and biochemical analyses inhibiting tumor proliferation by 66.7% compared to Erlotinib's 65.7%. So, compound 13b may serve as a promising anticancer activity through dual PARP-1/EGFR target inhibition.
One of 2019's biggest scientific challenges is the coronavirus disease (COVID-19). The current COVID-19 epidemic is still a point of interest of all researchers from every field in the hope of finding a way to have it under control. COVID-19 vaccine development is a lengthy procedure that requires several clinical studies to prove its efficacy and overcome the virus mutations. Personal Protective Equipment (PPE) as masks and gloves are essential for moving the battle out of one's body. Developing a highly efficient PPE is crucial, not only to reduce the spread of virus, but also to protect people who work at the frontline. Virus infection is one of the most serious public health problems facing the world today. Between now and then, several antiviral medicines have been tested to determine their effectiveness as prospective COVID-19 treatments. The rise of viral resistance, as well as the adverse effects associated with antiviral medications, are posing further hurdles, resulting in a decrease in their efficiency as antiviral treatments. This opens the possibility for developing an alternative antiviral material that is both safe and effective. When it comes to their potential to destroy a wide range of viruses, silver nanoparticles (Ag-NPs) laden fiber mats have emerged as a novel antiviral platform, according to the findings of the current study. In the past, Ag-NPs have been extensively examined for their antibacterial properties against a wide range of microorganisms. Their ability to combat hepatitis B and HIV has also been demonstrated to be encouraging, as has their ability to inhibit other viruses such as herpes simplex, monkey pox, and respiratory syncytial virus. Here, we tested the potential effect of silver nanoparticles as an alternative antiviral therapeutic based on their unique properties. When compared to imitative antivirals, elemental silver nanoparticles have the ability to attack many virus sites, reducing the likelihood of the virus developing resistance. Our group has been developing silver nanoparticles loaded on toilet paper seat sheets, cellulose membranes, polymer dressings, and cotton textiles in response to the persistent issue. The new generation of fiber mats will be thoroughly described and tested against SARS-CoV-2 virus. SEM, EDS, TEM, and DLS will be utilized to identify the shape of our fibers and estimate the particle size of the embedded nanoparticles.
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