A series of second-generation analogues for 2-(1-(2-(4-butylphenyl)-4-methylthiazol-5-yl)ethylidene)aminoguanidine (1) have been synthesized and tested against methicillin-resistant Staphylococcus aureus (MRSA). The compounds were designed with the objective of improving pharmacokinetic properties. This main aim has been accomplished by replacing the rapidly hydrolyzable Schiff-base moiety of first-generation members with a cyclic, unhydrolyzable pyrimidine ring. The hydrazide-containing analogue 17 was identified as the most potent analogue constructed thus far. The corresponding amine 8 was 8 times less active. Finally, incorporating the nitrogenous side chain within an aromatic system completely abolished the antibacterial character. Replacement of the n-butyl group with cyclic bioisosteres revealed cyclohexenyl analogue 29, which showed significant improvement in in vitro anti-MRSA potency. Increasing or decreasing the ring size deteriorated the antibacterial activity. Compound 17 demonstrated a superior in vitro and in vivo pharmacokinetic profile, providing compelling evidence that this particular analogue is a good drug candidate worthy of further analysis.

Broad bean mottle virus (BBMV) infects a wide range of hosts, resulting in significant production reductions. The lack of adequate and effective control methods involves implementing novel BBMV control strategies. Herein, we demonstrate the effect of different potassium concentrations (20, 40, and 60 mM) against BBMV in broad bean plants. Potassium could control BBMV infection in broad bean by inhibiting the virus. In addition, infection with BBMV caused a significant decrease in morphological criteria, SPDA, photosynthetic characteristics, phytohormones, and mineral content in broad bean leaves compared to control plants. The levels of reactive oxygen species (ROS) (hydrogen peroxide, hydroxyl radical, and oxygen anion) and ROS scavenging enzymes (catalase, superoxide dismutase, peroxidase, phenylaniline ammonia-lyase, chitinase, and 1,3 - glucanase) increased significantly in plants inoculated with BBMV alone or in the presence of K+. In addition, proline and phenolic compounds increased significantly after being infected with BBMV. In conclusion, treatment with a high potassium concentration (60 mM) alleviates the adverse effect of BBMV on broad bean plants by boosting secondary metabolites, phytohormones, and enzymatic antioxidants.

Bacterial resistance to antibiotics is presently one of the most pressing healthcare challenges and necessitates the discovery of new antibacterials with unique chemical scaffolds. However, the determination of the optimal balance between structural requirements for pharmacological action and pharmacokinetic properties of novel antibacterial compounds is a significant challenge in drug development. The incorporation of lipophilic moieties within a compound’s core structure can enhance biological activity but have a deleterious effect on drug-like properties. In this Article, the lipophilicity of alkynylphenylthiazoles, previously identified as novel antibacterial agents, was reduced by introducing cyclic amines to the lipophilic side chain. In this regard, substitution with methylpiperidine (compounds 14–16) and thiomorpholine (compound 19) substituents significantly enhanced the aqueous solubility profile of the new compounds more than 150-fold compared to the first-generation lead compound 1b. Consequently, the pharmacokinetic profile of compound 15 was significantly enhanced with a notable improvement in both half-life and the time the compound’s plasma concentration remained above its minimum inhibitory concentration (MIC) against methicillin-resistant Staphylococcus aureus (MRSA). In addition, compounds 14–16 and 19 were found to exert a bactericidal mode of action against MRSA and were not susceptible to resistance formation after 14 serial passages. Moreover, these compounds (at 2× MIC) were superior to the antibiotic vancomycin in the disruption of the mature MRSA biofilm. The modifications to the alkynylphenylthiazoles reported herein successfully improved the pharmacokinetic profile of this new series while maintaining the compounds’ biological activity against MRSA.

Viruses pose a serious threat to the sustainable production of economically important crops around the world. In the past 20 years, potato virus Y (PVY) emerged as a relatively new and very serious problem in potatoes, even though it is the oldest known plant virus. Multiple strains of the virus cause various symptoms on the leaves and tubers of potatoes, resulting in yield reduction and poor-quality tubers. Consequently, it would be very interesting to learn what causes systemic PVY resistance in plants. Natural compounds such as chitosan (CHT) and phosphorus have been developed as alternatives to chemical pesticides to manage crop diseases in recent years. In the current study, potato leaves were foliar-sprayed with chitosan and phosphorus to assess their ability to induce PVY resistance. Compared to untreated plants, the findings demonstrated a significant decrease in disease severity and PVY accumulation in plants for which CHT and P were applied. Every treatment includes significantly increased growth parameters, chlorophyll content, photosynthetic characteristics, osmoprotectants (glycine betaine, proline, and soluble sugar), non-enzymatic antioxidants (glutathione, phenols, and ascorbic acid), enzymatic antioxidants (peroxidase, superoxide dismutase, lipoxygenase, glutathione reductase, catalase, β-1,3 glucanase, and ascorbate peroxidase), phytohormones (gibberellic acid, indole acetic acid, jasmonic acid, and salicylic acid), and mineral content (phosphorus, nitrogen, and potassium), compared to infected plants. However, compared to PVY infection values, CHT and P treatments showed a significant decrease in malondialdehyde, DPPH, H2O2, O2, OH, and abscisic acid levels. In addition, increased expression levels of some regulatory defense genes, including superoxide dismutase (SOD), ascorbic acid peroxidase (APX), relative pathogenesis-related 1 basic (PR-1b), and relative phenylalanine ammonia-lyase (PAL), were found in all treated plants, compared to PVY-infected plants. Conclusion: Phosphorus is the most effective treatment for alleviating virus infections.

Sandy soils (containing > 50% sand) are widely distributed worldwide and are characterized by their poor structure, low organic matter, weak hydraulic and nutritional properties, and low crop productivity. Using a 2-year pot experiment, in this study, we investigated the effects of humic acid (HA) as a soil amendment and study two plant growth stimulants (PGSs), zinc oxide nanoparticles (ZnONPs), and L-tryptophan (L-TRP), as a foliar application on wheat grown in nutrient-poor sandy soil. Three HA rates (0 (HA0), 0.2 (HA0.2), and 0.4 (HA0.4) g kg−1 soil) and five PGS levels [control, 50 mg l−1 (ZnONPs50), 100 mg l−1 (ZnONPs100), 0.25 mmol l−1 (L-TRP0.25), and 0.5 mmol l−1 (L-TRP0.5)] were used. The soil hydro-physico-chemical properties, morpho-physiological responses, yield, and quality were measured. HA addition amended the soil structure by allowing rapid macroaggregate formation, decreasing bulk density and pH, and increasing porosity and electrical conductivity, thereby improving soil hydraulic properties. HA0.2 and HA0.4 additions improved growth, yield components, and grain minerals, resulting in higher grain yield by 28.3–54.4%, grain protein by 10.2–13.4%, wet gluten by 18.2–23.3%, and dry gluten by 23.5–29.5%, respectively, than HA0. Foliar application of ZnONPs or L-TRP, especially at higher concentrations compared to the control, noticeably recorded the same positive results as HA treatments. The best results were achieved through the integration of HA0.4 + ZnONPs100 or L-TRP0.5 to the tested nutrient-poor sandy soil. The interactive application of HA0.4 + ZnONPs100 or L-TRP0.5 and the use of mineral fertilizer, which is considered a surplus point in permaculture, can be recommended for sustainable wheat production in nutrient-poor sandy soil.