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The aim of this research work was to formulate and evaluate ciprofloxacin hydrochloride-loaded nanocarriers for treating dental infections and bone regeneration. Periodontal infection is associated with inflammation, soft tissue destruction, and bone loss. The objective of the study was to extract β tricalcium phosphate (β-TCP) from coral beach sand using the hydrothermal conversion method and load these nanocarriers with ciprofloxacin hydrochloride. The developed drug-loaded nanocarriers were evaluated for various parameters. In vitro drug-loading studies showed the highest drug loading of 71% for F1 with a drug: carrier ratio compared to plain ciprofloxacin hydrochloride gel. β-TCP and nanocarriers were evaluated for powder characteristics and the results were found to have excellent and fair flowability. In vitro drug release studies conducted over a period of 5 days confirmed the percentage drug release of 96% at the end of 120 h. Nanocarriers were found to be effective against S. aureus and E. coli showing statistically significant antibacterial activity at (* p < 0.05) significant level as compared to plain ciprofloxacin hydrochloride gel. The particle size of β-TCP and nanocarriers was found to be 2 µm. Fourier transform infra-red studies showed good compatibility between the drug and the excipients. Differential scanning calorimetry studies revealed the amorphous nature of the nanocarriers as evident from the peak shift. It is obvious from the XRD studies that the phase intensity was reduced, which demonstrates a decrease in crystallinity. Nanocarriers released the drug in a controlled manner, hence may prove to be a better option to treat dental caries as compared to conventional treatments.

The rapid spread of bacterial infection caused by Staphylococcus aureus has become a problem to public health despite the presence of past trials devoted to controlling the infection. Thus, the current study aimed to explore the chemical composition of the extract of endophytic fungus Aspergillus fumigatus , isolated from Albizia lucidior leaves, and investigate the antimicrobial activity of isolated metabolites and their probable mode of actions. The chemical investigation of the fungal extract via UPLC/MS/MS led to the identification of at least forty-two metabolites, as well as the isolation and complete characterization of eight reported metabolites. The antibacterial activities of isolated metabolites were assessed against S. aureus using agar disc diffusion and microplate dilution methods. Compounds ergosterol, helvolic acid and monomethyl sulochrin-4-sulphate showed minimal inhibitory concentration (MIC) values of 15.63, 1.95 and 3.90 µg/mL, respectively, compared to ciprofloxacin. We also report the inhibitory activity of the fungal extract on DNA gyrase and topoisomerase IV, which led us to perform molecular docking using the three most active compounds isolated from the extract against both enzymes. These active compounds had the required structural features for S. aureus DNA gyrase and topoisomerase IV inhibition, evidenced via molecular docking.

Purpose: The objective of our work was to prepare a potent and safe antimicrobial and anticancer agents, through synthesis of several peptides and examine their biological activities, namely as, cytotoxically potent and antimicrobial and antifungal agents., Introduction: Multidrug-resistant microbial strains have arisen against all antibiotics in clinical use. Infections caused by these bacteria threaten global public health and are associated with high mortality rates., Methods: The main backbone structure for the novel synthesized linear peptide is Nα-1, 3-benzenedicarbonyl-bis-(Amino acids)-X, ( 3-11 ). A computational docking study against DNA gyrase was performed to formulate a mode of action of the small compounds as antimicrobial agents., Results: The peptide-bearing methionine-ester ( 4 ) exhibited potent antimicrobial activity compared to the other synthesized compounds, while, peptide ( 8 ), which had methionine-hydrazide fragment was the most potent as antifungal agent against Aspergillus niger with 100% inhibition percent. Compounds ( 6 and 7 ) showed the highest potency against breast human tumor cell line "MCF-7" with 95.1% and 79.8% of cell inhibition, respectively. The nine compounds possessed weak to moderate antiproliferative effect over colon tumor cell line. The docking results suggest good fitting through different hydrogen bond interactions with the protein residues. In silico ADMET study also evaluated and suggested that these compounds had promising oral bioavailability features., Conclusion: The tested compounds need further modification to have significant antimicrobial and antitumor efficacy compared to the reference drugs., Competing Interests: The authors declare no conflicts of interest in this work., (© 2021 Naglah et al.)

A series of Bis -pyrazole Schiff bases ( 6a - d and 7a - d ) and mono-pyrazole Schiff bases ( 8a - d and 9a - d ) were designed and synthesized through the reaction of 5-aminopyrazoles 1a - d with aldehydes 2 - 5 using mild reaction condition with a good yield percentage. The chemical structure of newly formed Schiff bases tethered pyrazole core was confirmed based on spectral and experimental data. All the newly formed pyrazole Schiff bases were evaluated against eight pathogens (Gram-positive, Gram-negative, and fungi). The result exhibited that, most of them have good and broad activities. Among those, only six Schiff bases ( 6b , 7b , 7c , 8a , 8d , and 9b ) displayed MIC values (0.97-62.5 µg/mL) compared to Tetracycline (15.62-62.5 µg/mL) and Amphotericin B (15.62-31.25 µg/mL), MBC values (1.94-87.5 µg/mL) and selectivity to tumor cell than normal cells. Immunomodulatory activities showed that the promising Schiff bases increase the immunomodulator effect of defense cell and the Schiff base 8a is the highest one by (Intra. killing activity = 136.5 ± 0.3%) having a pyrazole moiety as well as amide function (O=C-NH 2 ) and piperidinyl core. Furthermore, the most potent one exhibited broad activity depending on both MIC and MBC values. Moreover, to study the mechanism of these pyrazole Schiff bases, two active Schiff bases 8a and 9b from six derivatives were introduced to study the enzyme assay as dihydrofolate reductase (DHFR) on E. coli organism and DNA gyrase with two different organisms, S. aureus and B. subtilis , to determine the inhibitory activities with lower values in the case of DNA gyrase ( 8a and 9b ) or nearly as DHFR compound 9b , while pyrazole 8a showed excellent inhibitory against all enzyme assay. The molecular docking study against dihydrofolate reductase and DNA gyrase were performed to study the binding between active site in the pocket with the two Schiff bases ( 8a and 9b ) that exhibited good binding affinity with different bond types as H-bonding, aren-aren, and arene-cation interaction as well as study the physicochemical and pharmacokinetic properties of the two active Schiff bases 8a and 9b .

New dithiocarbamate chalcone-based derivatives were synthesized, their structures were elucidated using different spectroscopic techniques. They were subjected to antimicrobial screening against selected Gram negative bacteria focusing on microbial resistance. Bacterial resistance was targeted via phosphoethanolamine transferase enzyme. Most of the synthesized compounds showed equal or higher activity to colistin standard. Compound 24 proved to be the most active candidate with MIC of 8 µg/ml against both Ps12 and K4 and MBC of 32 µg/ml against Ps12 and 16 µg/ml against K4 Molecular docking study showed that 20, 22, 24 and 25 had good binding affinity with active site residues via Thr280. DNA macromolecule was further targeted. Compounds 28 and 34 were recorded to have better DNA binding than doxurubucin with IC 50 of 27.48 and 30.97 µg/ml respectively, suggesting that it could have a role in their higher antibacterial effect. Their docking into DNA has shown a clear intercalation matching with antibacterial data. Pharmacokinetics parameters of active compounds showed that they have better absorption through GIT., (Copyright © 2019. Published by Elsevier Inc.)