Novel 1,2,3-Triazole-sulphadiazine-ZnO Hybrids as Potent Antimicrobial Agents against Carbapenem Resistant Bacteria.

Bacterial pneumonia is considered one of the most virulent diseases with high morbidity and mortality rates, especially in hospitalized patients. Moreover, bacterial resistance increased over the last decades which limited the therapy options to carbapenem antibiotics. Hence, the metallo-ß-lactamase-producing bacteria were deliberated as the most deadly and ferocious infectious agents. Sulphadiazine-ZnO hybrids biological activity was explored in vitro and in vivo against metallo-ß-lactamases (MBLs) producing Klebsiella pneumoniae. Docking studies against NDM-1 and IMP-1 MBLs revealed the superior activity of the 3a compound in inhibiting both MBLs enzymes in a valid reliable docking approach. The MBLs inhibition enzyme assay revealed the remarkable sulphadiazine-ZnO hybrids inhibitory effect against NDM-1 and IMP-1 MBLs. The tested compounds inhibited the enzymes both competitively and noncompetitively. Compound 3b-ZnO showed the highest antibacterial activity against the tested metallo-ß-lactamase producers with an inhibition zone (IZ) diameter reaching 43 mm and a minimum inhibitory concentration (MIC) reaching 2 µg/mL. Sulphadiazine-ZnO hybrids were tested for their in vitro cytotoxicity in a normal lung cell line (BEAS-2Bs cell line). Higher cell viability was observed with 3b-ZnO. Biodistribution of the sulphadiazine-ZnO hybrids in the lungs of uninfected rats revealed that both [124I]3a-ZnO and [124I]3b-ZnO hybrids remained detectable within the rats' lungs after 24 h of endotracheal aerosolization. Moreover, the residence duration in the lungs of [124I]3b-ZnO (t1/2 4.91 h) was 85.3%. The histopathological investigations confirmed that compound 3b-ZnO has significant activity in controlling bacterial pneumonia infection in rats.

Synthesis, Characterization and Nanoformulation of Novel Sulfonamide-1,2,3-triazole Molecular Conjugates as Potent Antiparasitic Agents.

Toxoplasma gondii (T. gondii) is a highly prevalent parasite that has no gold standard treatment due to the poor action or the numerous side effects. Focused sulfonamide-1,2,3-triazole hybrids 3a-c were wisely designed and synthesized via copper catalyzed 1,3-dipolar cycloaddition approach between prop-2-yn-1-alcohol 1 and sulfa drug azides 2a-c. The newly synthesized click products were fully characterized using different spectroscopic experiments and were loaded onto chitosan nanoparticles to form novel nanoformulations for further anti-Toxoplasma investigation. The current study proved the anti-Toxoplasma effectiveness of all examined compounds in experimentally infected mice. Relative to sulfadiazine, the synthesized sulfonamide-1,2,3-triazole (3c) nanoformulae demonstrated the most promising result for toxoplasmosis treatment as it resulted in 100% survival, 100% parasite reduction along with the remarkable histopathological improvement in all the studied organs.

In vivo bio-distribution and acute toxicity evaluation of greenly synthesized ultra-small gold nanoparticles with different biological activities.

Ultra-small gold nanoparticles (Au-NPs) "≤ 10 nm diameters" have potent biomedical applications. Hence, the present study aimed to greenly synthesize ultra-small gold nanoparticles using Egyptian propolis extract. Different biological activities, in vivo bio-distribution and acute toxicity study were assessed. Results revealed that, Egyptian propolis extract can successfully synthesize the highly pure and stable ultra-small Au-NPs with average diameter 7.8 nm. In vitro antimicrobial and antimycobacterial activities revealed the powerful effect of the prepared Au-NPs. Moreover, the cytotoxic effect on human cancer cell lines revealed the potent inhibition of the cancer cells' proliferation with high reactive oxygen species-mediated apoptosis induction. In vivo bio-distribution and acute toxicity studies were performed (10 and 100 mg/kg doses) in male albino rats. The ultra-small Au-NPs showed low or no toxicity upon using the Au-NPs low dose. The mean area accumulation (%) of the Au-NPs was higher in the liver, kidney, and brain tissues (4.41, 2.96, and 0.3 times, respectively) treated with high Au-NPs dosage compared to those treated with the low dose. Surprisingly, Au-NP accumulation in brain tissue was observed in the glial cells only. Accordingly, the low dose (10 mg/kg) of Au-NPs can be used safely in a variety of biomedical applications.

Synthesis, structural elucidation, DFT calculation, biological studies and DNA interaction of some aryl hydrazone Cr3+, Fe3+, and Cu2+ chelates.

The current research focuses on the treatment of Cr(III), Fe(III) and Cu(II) metal ions with aryl hydrazone ligand named (E)-4-(((diphenylmethylene)hydrazono)methyl)benzene-1,3-diol (DPHB) to afford four novel solid complexes with high yields. Different characterization approaches, including infrared, UV-visible, and NMR spectroscopies, elemental analyses, and thermal gravimetric analysis (TGA), revealed that all mononuclear crystalline metal chelates with good thermal stability had a six-coordination with octahedral geometry. Density Functional Theory (DFT) computations were used and provided a reasonable explanation for these metal chelates' electrical and structural features. Furthermore, investigations of electronic absorption spectroscopy, hydrodynamics, and electrophoresis demonstrated that these new compounds interact with calf thymus deoxyribonucleic acid (CT-DNA) in a variety of ways. As a result, the Kb and ∆Gb≠ values of such interactions were in the following order: DPHBCu > DPHBCr > DPHBFe complex. Additionally, the novel metal chelates have been studied anti-bathogenically and found to be significantly effective compared to the comparable DPHB hydrazone ligand. The anti-proliferative activities of the investigated compounds were also evaluated against different lines of cancer cells and exhibited significant cytotoxic activity. In addition, observations of antioxidant activity suggest that antioxidant activity relative to ordinary ascorbic acid was demonstrated in the molecule.

Water Treatment from MB Using Zn-Ag MWCNT Synthesized by Double Arc Discharge.

A new type of nano-adsorbent zinc-silver nanoparticles ornamented by multi-walled carbon nanotubes (Zn-Ag MWCNT) was efficiently synthesized by double arc discharge using a newly designed rotating cylinder electrode. Zn-Ag MWCNT was characterized by different instrumental methods to get information about the sample shape, size, and crystallinity. Without irradiation, Zn-Ag MWCNT indicated significant potential for elimination against methylene blue (MB) which is dissolved in deionized water. When the adsorbent concentration was 0.1 g/L at normal 8 pH, the Zn-Ag MWCNTs were efficient in removing 97% of the MB from 40 mg/L that was dissolved in water for 10 min. The dye removal activity of (Zn-Ag) decorated MWCNTs was attributed to the influence of silver and zinc nanoparticles on the MWCNTs. Finally, this approach was both cost-effective and efficient.

Novel Synthesis of Titanium Oxide Nanoparticles: Biological Activity and Acute Toxicity Study.

Titanium oxide nanoparticles (TiO2 NPs) have been attracting numerous research studies due to their activity; however, there is a growing concern about the corresponding toxicity. Here in the present study, titanium oxide nanoparticles were newly synthesized using propolis extract followed by antimicrobial activity, cytotoxicity assay using human cancer cell lines, and acute toxicity study. The physicochemical characterization of the newly synthesized TiO2 NPs had average size = 57.5 nm, PdI = 0.308, and zeta potential = -32.4 mV. Antimicrobial activity assessment proved the superior activity against Gram-positive compared to Gram-negative bacteria and yeast (lowest MIC values 8, 32, and 32, respectively). The newly synthesized TiO2 NPs showed a potent activity against the following human cancer cell lines: liver (HepG-2) (IC50 8.5 µg/mL), colon (Caco-2), and breast (MDA-MB 231) (IC50 11.0 and 18.7 µg/mL). In vivo acute toxicity study was conducted using low (10 mg/kg) and high (1000 mg/kg) doses of the synthesized TiO2 NPs in albino male rats. Biochemistry and histopathology of the liver, kidney, and brain proved the safety of the synthesized TiO2 NPs at low dose while at high dose, there was TiO2 NPs deposit in different vital organs except the cerebral tissue.

Design and Synthesis of Novel Imidazole Derivatives Possessing Triazole Pharmacophore with Potent Anticancer Activity, and In Silico ADMET with GSK-3ß Molecular Docking Investigations.

A library of novel imidazole-1,2,3-triazole hybrids were designed and synthesized based on the hybrid pharmacophore approach. Therefore, copper(I)catalyzed click reaction of thiopropargylated-imidazole 2 with several organoazides yielded two sets of imidazole-1,2,3-triazole hybrids carrying different un/functionalized alkyl/aryl side chains 4a-k and 6a-e. After full spectroscopic characterization using different spectral techniques (IR, 1H, 13C NMR) and elemental analyses, the resulted adducts were screened for their anticancer activity against four cancer cell lines (Caco-2, HCT-116, HeLa, and MCF-7) by the MTT assay and showed significant activity. In-silico molecular docking study was also investigated on one of the prominent cancer target receptors, i.e., glycogen synthase kinase-3ß (GSK-3ß), revealing a good binding interaction with our potent compound, 4k and was in agreement with the in vitro cytotoxic results. In addition, the ADMET profile was assessed for these novel derivatives to get an insight on their pharmacokinetic/dynamic attributes. Finally, this research design and synthesis offered click chemistry products with interesting biological motifs mainly 1,2,3 triazoles linked to phenyl imidazole as promising candidates for further investigation as anticancer drugs.

Design of Novel Oligomeric Mixed Ligand Complexes: Preparation, Biological Applications and the First Example of Their Nanosized Scale.

A successful oligomerization of ternary metal complexes, cobalt (II), nickel (II), copper (II), zinc (II), chromium (III) and ferric sulfate (III) with nitrilotriacetic acid (NTA) as a primary ligand and glutamic acid as a secondary ligand, has been demonstrated. The formation of oligomers arose from the presence of the sulfate moiety, which operates as a bridged bidentate ligand that coordinates with other metal moieties. The novel oligomers exhibited octahedral structures, which bonded together through the sulfate moiety. In silico predictions were conducted to gauge the bioactivity, physico-chemical and pharmacokinetic properties. The biological activities of these oligomers as well as their tumor inhibitory behavior have been explored. This work also presents a facile and novel method of preparing these materials in nanosize, using Cetyltrimethylammonium bromide (CTAB) and polyvinyl alcohol (PVA) as capping ligands. The size and shape of the nanomaterials have been confirmed using the transmission electron microscope (TEM) and the scanning electron microscope (SEM).