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Significant postharvest losses and food safety issues persist in many developing nations, primarily due to fungal activities, including mycotoxin production. In this study, green synthesised zinc oxide nanoparticles (ZnO-NPs) were prepared from leaf extracts of Syzygium cordatum (ZnO 1), Lippia javanica (ZnO 2), Bidens pilosa (ZnO 3), and Ximenia caffra (ZnO 4). Physicochemical characteristics of the ZnO-NPs were determined using X-ray diffraction (XRD), Fourier transmission Infrared spectroscopy and ultraviolet–visible (UV–vis) spectroscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The XRD analysis confirmed the presence of a wurtzite crystal structure in the hexagonal shape of the ZnO nanoparticles (NPs), with an average size ranging between 25 and 43 nm. The microscopic examination of the morphology revealed the presence of spherical particles with sizes ranging from 37 to 47 nm in diameter. The antifungal efficacy of the ZnO-NPs was assessed against pathogenic plant fungi, including Botrytis sp. (STEU 7866), Penicillium sp. (STEU 7865), and Pilidiella granati (STEU 7864), using the poisoned food technique. Further antifungal evaluation of the ZnOPs was performed using the broth microdilution assay. A significant interaction between the type of ZnO-NPs and fungal species was observed, with the highest susceptibility in Mucor sp. to ZnO 2, achieving over 50% inhibition. Penicillium sp. also showed high susceptibility to all ZnO-NPs. Molecular docking results confirmed the strong H-bonding interactions of ZnO-NPs with fungal receptors in Mucor sp. and Penicillium sp., Botrytis sp. and P. granati exhibited the least susceptibility. Further tests revealed that ZnO 2 exhibited the highest inhibitory effect on Botrytis sp., with a low minimum inhibitory concentration (MIC) of 25 µg/mL, attributed to its larger positive zeta potential. This study indicates that ZnO NPs, particularly those mediated using Lippia javanica (ZnO 2), have promising potential as effective antifungal agents, which could play a significant role in reducing postharvest decay and losses. [ABSTRACT FROM AUTHOR]

The use of protease inhibitors in human immunodeficiency virus type 1 (HIV-1) treatment is limited by adverse effects, including metabolic complications. To address these challenges, efforts are underway in the pursuit of more potent and less toxic HIV-1 protease inhibitors. Repurposing existing drugs offers a promising avenue to expedite the drug discovery process, saving both time and costs compared to conventional de novo drug development. This study screened FDA-approved and investigational drugs in the DrugBank database for their potential as HIV-1 protease inhibitors. Molecular docking studies and cell-based assays, including anti-HIV-1 in vitro assays and XTT cell viability tests, were conducted to evaluate their efficacy. The study findings revealed that CBR003PS, an antibiotic currently in clinical use, and CBR013PS, an investigational drug for treating endometriosis and uterine fibroids, exhibited significant binding affinity to the HIV-1 protease with high stability. Their EC50 values, measured at 100% cell viability, were 9.4 nM and 36.6 nM, respectively. Furthermore, cell-based assays demonstrated that these two compounds showed promising results, with therapeutic indexes higher than 32. In summary, based on their favorable therapeutic indexes, CBR003PS and CBR013PS show potential for repurposing as HIV-1 protease inhibitors. [ABSTRACT FROM AUTHOR]

The human immunodeficiency virus type 1 (HIV-1) has continued to be a global concern. With the new HIV incidence, the emergence of multi-drug resistance and the untoward side effects of currently used anti-HIV drugs, there is an urgent need to discover more efficient anti-HIV drugs. Modern computational tools have played vital roles in facilitating the drug discovery process. This research focuses on a pharmacophore-based similarity search to screen 111,566,735 unique compounds in the PubChem database to discover novel HIV-1 protease inhibitors (PIs). We used an in silico approach involving a 3D-similarity search, physicochemical and ADMET evaluations, HIV protease-inhibitor prediction (IC50/percent inhibition), rigid receptor–molecular docking studies, binding free energy calculations and molecular dynamics (MD) simulations. The 10 FDA-approved HIV PIs (saquinavir, lopinavir, ritonavir, amprenavir, fosamprenavir, atazanavir, nelfinavir, darunavir, tipranavir and indinavir) were used as reference. The in silico analysis revealed that fourteen out of the twenty-eight selected optimized hit molecules were within the acceptable range of all the parameters investigated. The hit molecules demonstrated significant binding affinity to the HIV protease (PR) when compared to the reference drugs. The important amino acid residues involved in hydrogen bonding and п-п stacked interactions include ASP25, GLY27, ASP29, ASP30 and ILE50. These interactions help to stabilize the optimized hit molecules in the active binding site of the HIV-1 PR (PDB ID: 2Q5K). HPS/002 and HPS/004 have been found to be most promising in terms of IC50/percent inhibition (90.15%) of HIV-1 PR, in addition to their drug metabolism and safety profile. These hit candidates should be investigated further as possible HIV-1 PIs with improved efficacy and low toxicity through in vitro experiments and clinical trial investigations. [ABSTRACT FROM AUTHOR]

The drugs used for treating bone diseases (BDs), at present, elicit hazardous side effects that include certain types of cancers and strokes, hence the ongoing quest for the discovery of alternatives with little or no side effects. Natural products (NPs), mainly of plant origin, have shown compelling promise in the treatments of BDs, with little or no side effects. However, the paucity in knowledge of the mechanisms behind their activities on bone remodeling has remained a hindrance to NPs' adoption. This review discusses the pathological development of some BDs, the NP-targeted components, and the actions exerted on bone remodeling signaling pathways (e.g., Receptor Activator of Nuclear Factor κ B-ligand (RANKL)/monocyte/macrophage colony-stimulating factor (M-CSF)/osteoprotegerin (OPG), mitogen-activated protein kinase (MAPK)s/c-Jun N-terminal kinase (JNK)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), Kelch-like ECH-associated protein 1 (Keap-1)/nuclear factor erythroid 2–related factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1), Bone Morphogenetic Protein 2 (BMP2)-Wnt/β-catenin, PhosphatidylInositol 3-Kinase (PI3K)/protein kinase B (Akt)/Glycogen Synthase Kinase 3 Beta (GSK3β), and other signaling pathways). Although majority of the studies on the osteoprotective properties of NPs against BDs were conducted ex vivo and mostly on animals, the use of NPs for treating human BDs and the prospects for future development remain promising. [ABSTRACT FROM AUTHOR]

Background and Purpose: The preponderance of microbial infections remains a global challenge. In the present study, synthesis of novel cysteine-based antimicrobial agents and their biological evaluation is reported., Experimental Approach: The reaction of p -toluenesulphonyl chloride with cysteine afforded 2-{[(4-methylphenyl)sulphonyl]amino}-3-sulphanylpropanoic acid (3) which was acetylated based on Lumiere-Barbier method using acetic anhydride. The ammonolysis of the acetylated compound (4) gave the carboxamide derivative ( 5 ) which reacted with aniline, aminopyridine and diaminopyrimidine via nickel catalyzed Buchwald-Hartwig amidation reaction to afford compounds 6a, 6b, and 6c , respectively. The compounds were characterized using FTIR, 1 H-NMR, 13 C-NMR, and elemental analysis. The in vitro antimicrobial activities were determined. Their physicochemical properties were generated in silico and the molecular docking studied bacterial and fungal infections., Findings/results: Compounds 4, 6b, and 6c exhibited excellent in vitro antibacterial activities while compound 4 had the best antifungal activities. From the in silico antimicrobial results, compound 3 had a better binding affinity (-10.95 kcal/mol) than penicillin (-10.89 kcal/mol) while compounds 3 and 4 had binding affinities (-10.07 and -10.62kcal/mol) comparable to ketoconazole (-10.85 kcal/mol)., Conclusion and Implication: All the synthesized compounds exhibited significant antibacterial and antifungal activities and were confirmed to be potential antimicrobial agents., Competing Interests: The authors declared no conflicts of interest in this study., (Copyright: © 2021 Research in Pharmaceutical Sciences.)