In the last four decades, nanotechnology has gained momentum with no sign of slowing down. The application of inventions or products from nanotechnology has revolutionised all aspects of everyday life ranging from medical applications to its impact on the food industry. Nanoparticles have made it possible to significantly extend the shelf lives of food product, improve intracellular delivery of hydrophobic drugs and improve the efficacy of specific therapeutics such as anticancer agents. As a consequence, nanotechnology has not only impacted the global standard of living but has also impacted the global economy. In this review, the characteristics of nanoparticles that confers them with suitable and potentially toxic biological effects, as well as their applications in different biological fields and nanoparticle-based drugs and delivery systems in biomedicine including nano-based drugs currently approved by the U.S. Food and Drug Administration (FDA) are discussed. The possible consequence of continuous exposure to nanoparticles due to the increased use of nanotechnology and possible solution is also highlighted.

Multidrug-resistant (MDR) Salmonella remains a significant global health threat. This study aimed to explore the potential of essential oil components as novel inhibitors of the Salmonella MDR efflux pumps AcrAB and AcrD. Salmonella isolates were characterized for serotype, antibiotic resistance, and efflux pump activity. Essential oil components were screened for inhibitory effects using phenotypic and genotypic methods. In silico docking and molecular dynamics simulations were conducted to investigate binding interactions and stability. Salmonella Typhimurium was the predominant serotype with high MDR rates. Efflux pump activity was prevalent. Cumin and cinnamon oils demonstrated promising inhibitory effects on these pumps. Molecular docking simulations revealed strong binding affinities of analyzed compounds to the AcrAB and AcrD binding pocket. The 2-methyl-1-(p-tolyl)propan-2-ol exhibited higher stability within the AcrAB binding pocket compared to (1S,3R,5R)-1-isopropyl-4-methylenebicyclo[3.1.0]hexan-3-ol within the AcrD binding pocket. Treatment with these oils significantly downregulated efflux pump genes (robA, acrB, mdtB, acrF, acrD, soxS, mdsB, marA). The novel approach of combining in silico and molecular dynamics simulations with precise gene expression analysis provides a valuable framework for future studies aimed at combating MDR Salmonella efflux pumps.

The present investigation describes the design strategy and synthesis of novel thienopyrimidine compounds in addition to their anticancer activity targeting tyrosine kinase FLT3 enzyme. The synthesized compounds were subjected to a cytotoxic study where compounds 9a and 9b showed the most potent cytotoxicity against HT-29, HepG-2, and MCF-7 cell lines reflected by their IC₅₀ values for 9a (1.21 ± 0.34, 6.62 ± 0.7 and 7.2 ± 1.9 μM), for 9b (0.85 ± 0.16, 9.11 ± 0.3 and 16.26 ± 2.3 μM) and better than that of reference standard which recorded (1.4 ± 1.16, 13.915 ± 2.2, and 8.43 ± 0.5 μM), respectively. Compounds’ selectivity to malignant cells was determined using selectivity assay, interestingly, all the tested compounds demonstrated an excellent selectivity index (SI) range from 20.2 to 99.7. Target in-silico prediction revealed the FLT3 kinase enzyme was the kinase enzyme of highest probability. Molecular docking studies were performed on the prepared compounds which showed promising binding affinity for FLT3 kinase enzyme and the main interactions between the synthesized ligands and kinase active site were similar to those between the co-crystallized ligand and the receptor. Further biological exploration was performed using in-vitro FLT3 kinase enzyme inhibition assay. The results showed that the 2-morpholinoacetamido derivative 10a exhibited highest FLT3 inhibitory activity among the tested compounds followed by compound 9a then 12. Pharmacokinetic assessment disclosed that all the investigated compounds were considered as “drug-like” molecules with promising bioavailability.

This work describes the synthesis and anticancer activity against kinase enzymes of newly designed thiophene and thieno[2,3-d]pyrimidine derivatives, along with their potential to activate autophagic and apoptotic cell death in cancer cells. The designed compounds were scanned for their affinity for kinases. The results were promising with affinity ranges from 46.7% to 13.3%. Molecular docking studies were performed, and the compounds were then screened for their antiproliferative effects. Interestingly, compounds 8 and 5 resulted in higher cytotoxic effects than the reference standard against MCF-7 and HepG-2. The compounds were evaluated for their induction of apoptosis and/or necrosis on HT-29 and HepG-2. Three compounds induced significant early apoptosis compared to untreated control HT-29 cells, and four derivatives were more significant compared to untreated HepG-2 cells. We further investigated the effect of four compounds on the autophagy process within HT-29, HepG-2, and MCF-7 cells with flow cytometry. Similar to the apoptosis results, compound 5 showed the highest autophagic induction among all compounds. The potential inhibitory activity of the synthesized compounds on kinases was assessed. Screened compounds showed inhibition activity ranging from 41.4% to 83.5%. Compounds recorded significant inhibition were further investigated for their specific FLT3 kinase inhibitory activity. Noticeably, Compound 5 exhibited the highest inhibitory activity against FLT3.

This work describes the design and synthesis of new hybrids of thienopyrimidine and sulfonamides. The binding affinity of the prepared compounds to FGFR-1 enzyme and caspase-3 was investigated via molecular docking. The cytotoxic effect was estimated for the synthesized compounds against human breast cancer cell lines (MCF-7 and MDA-MB231) using Doxorubicin as a reference. All the tested compounds exhibited moderate to excellent anticancer efficacy against both tested cell lines, among which 3b and 4bi were the best. All the synthesized compounds exhibited distinguishing selectivity index values greater than Doxorubicin. The influence of the new hybrids under inquiry was further examined on both FGFR-1 and Caspase-3. The results revealed that compound 3b showed observed concordance between anti-proliferative activity and Caspase-3 activity. In respect to the compounds’ effect on the apoptosis, compound 3b significantly increased the population of late apoptotic cells and necrotic cells. In silico pharmacokinetic investigation revealed that compound 3b showed the best intestinal absorption, BBB permeability, and, along with 4bi and 4bii, the best CNS penetrability.

This work describes the synthesis and the cytotoxic evaluation of thiophene and thienopyrimidine derivatives. The investigated compound was subjected to target prediction that indicated its high affinity to kinases and to Janus kinase 2 (JAK2) specifically. Molecular docking screening was performed on three different JAK2 proteins downloaded from the Protein Data Bank (PDB: 5AEP, 4C62 and 3ZMM). In vitro kinase inhibitory activity was evaluated and then compound cytotoxicity was performed on three different cancerous cell lines (HT-29, HepG-2, and MCF-7). Marked cytotoxic activity of the thienopyrimidine derivative against the HepG-2 cell line was demonstrated, reflected by its IC₅₀ value of 8.001 ± 0.0445 μM, which is better than that of the reference standard (IC₅₀ 13.91 ± 2.170 μM). Pharmacokinetic studies revealed good well permeability and GI absorption with no violations against Lipinski’s rule.