Synthesis and in vitro antimicrobial activity of new steroidal hydrazone derivatives

Background For many years, various drugs have been used for the treatment of infectious diseases but some bacterial microorganisms have induced resistance to several drugs. In a search of new antimicrobial agents, a series of new steroidal hydrazones were designed and synthesized. Result The structures of the compounds were established based on the spectral data. The in vitro antimicrobial activity of some newly synthesized compounds against bacteria and fungi was studied. Conclusion New compounds showed better or similar antimicrobial activity. Designing more efficient steroidal hydrazones from ketosteroid based on the current study may successfully lead to the development of antimicrobial agent. Graphical abstract

Synthesis of Novel Thiazole Derivatives Bearing β-Amino Acid and Aromatic Moieties as Promising Scaffolds for the Development of New Antibacterial and Antifungal Candidates Targeting Multidrug-Resistant Pathogens

Rapidly growing antimicrobial resistance among clinically important bacterial and fungal pathogens accounts for high morbidity and mortality worldwide. Therefore, it is critical to look for new small molecules targeting multidrug-resistant pathogens. Herein, in this paper we report a synthesis, ADME properties, and in vitro antimicrobial activity characterization of novel thiazole derivatives bearing β-amino acid, azole, and aromatic moieties. The in silico ADME characterization revealed that compounds 1–9 meet at least 2 Lipinski drug-like properties while cytotoxicity studies demonstrated low cytotoxicity to Vero cells. Further in vitro antimicrobial activity characterization showed the selective and potent bactericidal activity of 2a–c against Gram-positive pathogens (MIC 1–64 µg/mL) with profound activity against S. aureus (MIC 1–2 µg/mL) harboring genetically defined resistance mechanisms. Furthermore, the compounds 2a–c exhibited antifungal activity against azole resistant A. fumigatus, while only 2b and 5a showed antifungal activity against multidrug resistant yeasts including Candida auris. Collectively, these results demonstrate that thiazole derivatives 2a–c and 5a could be further explored as a promising scaffold for future development of antifungal and antibacterial agents targeting highly resistant pathogenic microorganisms.

In vitro antimicrobial activity screening of new Heterocyclic compounds derived from 5-bromo-2,3-di(furan-2-yl)-1h-indole

This article describes the antimicrobial activity evaluation of new heterocyclic compounds derived from 5-bromo-2,3-di(furan-2-yl)-1h-indole. Heterocyclic moiety serve as perfect framework on which pharmacophores can be effectively attached to produce novel drugs. New compounds were obtained on the basis of derivatives including 1H-indole-2,3-dione derivatives. Acid-catalyzed, three-component reaction (Belinelli synthesis) between 5-bromo-2,3-di(furan-2-yl)1H-indole, acetylacetone and semi carbazide, thiosemicarbazone, urea, thiourea, guanidine constitutes a rapid and facile synthesis of corresponding tetrahydro pyrimidines, which are interesting compounds with a potential for pharmaceutical application. Antimicrobial tests revealed high antibacterial activity of obtained derivatives. The synthesized compounds have been screened for their in vitro antimicrobial activity against various strains of bacteria and fungi. Keywords: Vitro; Heterocyclic Compounds; Antimicrobial

In Vitro Antimicrobial Activity of the Siderophore Cephalosporin Cefiderocol against Acinetobacter baumannii Strains Recovered from Clinical Samples

Background: Cefiderocol is a siderophore cephalosporin that exhibits antimicrobial activity against most multi-drug resistant Gram-negative bacteria, including Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia. Methods: A total of 20 multidrug-resistant A. baumannii strains were isolated from 2020 to 2021, molecularly characterized and tested to assess the in vitro antibacterial activity of cefiderocol. Thirteen strains were carbapenem-hydrolysing oxacillinase OXA-23-like producers, while seven were non-OXA-23-like producers. Minimum inhibitory concentrations (MICs) were determined by broth microdilution, considered as the gold standard method. Disk diffusion test was also carried out using iron-depleted CAMHB plates for cefiderocol. Results: Cefiderocol MICs ranged from 0.5 to 1 mg/L for OXA-23-like non-producing A. baumannii strains and from 0.25 to >32 mg/L for OXA-23-like producers, using the broth microdilution method. Cefiderocol MIC90 was 8 mg/L. Diameter of inhibition zone of cefiderocol ranged from 18 to 25 mm for OXA-23-like non-producers and from 15 to 36 mm for OXA-23-like producers, using the diffusion disk method. A large variability and a low reproducibility were observed during the determination of diameter inhibition zone. Molecular characterization showed that all isolates presented the ISAba1 genetic element upstream the blaOXA-51. Among OXA-23-like non-producers, four were blaOXA-58 positive and two were negative for all the resistance determinants analyzed. Conclusions: Cefiderocol showed in vitro antimicrobial activity against both carbapenem-susceptible and non-susceptible A. baumannii strains, although some OXA-23-like producers were resistant. Further clinical studies are needed to consolidate the role of cefiderocol as an antibiotic against MDR A. baumannii.

In Vitro Antimicrobial Activity Evaluation of a Novel Fitostimoline® Plus Spray Formulation

Wound contaminants are the main cause of healing delay and infection in both chronic and acute wounds; for this reason, the microbial infection management in wound healing is one of the most important components for an effective standard of care. The wound contaminants are most likely to originate from the environment and from the surrounding skin lesion, and to date, the most frequent bacteria isolated are Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae. In order to counteract and control these contaminants, the standard care includes topical antiseptic agents. The most commonly used include iodine-releasing agents (e.g., povidone-iodine), hydrogen peroxide, and polyhexanide. This study aims to investigate the in vitro antibacterial activity of a novel topical spray (Fitostimoline® Plus spray) based on 0.1% polyhexanide and Rigenase® against S. aureus, P. aeruginosa, K. pneumoniae, and the combination of S. aureus and K. pneumoniae. The in vitro antimicrobial activity of Fitostimoline® Plus spray was evaluated by the agar disk diffusion assay, quantitative suspension test, and quantitative carrier test, demonstrating that Fitostimoline® Plus spray is able to kill 99.9% bacteria. These results support the microbiological characterization of Fitostimoline® Plus spray confirming the antibacterial activity of polyhexanide (PHMB).

In vitro Antimicrobial Activity of Ethanolic Leaf Extracts of Hibiscus Asper Hook. F. and Hibiscus Sabdariffa L. on some Pathogenic Bacteria

Purpose: The study aims to assess the antimicrobial activity of ethanolic leaf extracts of Hibiscus asper and Hibiscus sabdariffa against eight bacterial isolates. Materials and Methods: An in vitro Antimicrobial activity of ethanolic leaf extract of the two plants against eight nosocomical and pathogenic bacteria viz; Pseudomonas aeruginosa (PAE), Proteus vulgaris (PVU), Klebsiella aerogenes (KAE), Staphylococcus aureus (SAU), Bacillus cereus (BCE), Escherichia coli (ECO), Moraxella catarrhalis (MCA) and Salmonella typhi (STY) was carried out using agar well diffusion assay with the concentration range of 3.13 – 100 mg/mL. Results: H. asper and H. sabdariffa showed significant difference (p< 0.05) in antimicrobial activity against BCE over the rest of the isolates. Inhibition zone diameters exhibited by the isolates to ethanolic leaf extract of H. asper was in descending order of BCE (15.00 ± 1.00a) >ECO (11.67 ± 0.58b) >SAU (7.67 ± 0.58c) >PAE (6.67 ± 0.58d) >STY (5.67 ± 0.58e) while that of H. sabdariffa was in the order BCE (15.33 ± 1.15a) > MCA (11.33 ± 1.15b) > SAU (11.00 ± 1.00bc) > KAE (9.67 ± 0.58c) > PAE (8.00 ± 1.00d) >PVU (7.67 ± 0.57e). PVU, KAE and MCA were resistant to the extract of H. asper while only STY was resistant to that of H. sabdariffa. Conclusion: H. sabdariffa extract demonstrated higher antimicrobial activity against the selected bacterial isolates than H. asper. However, the two extracts minimum inhibition concentrations (MICs) ranged from 25 mg/mL to 12.5 mg/mL. This is worthy of further exploration by pharmacological industries in the formulation of potent broad spectrum antibiotics for combating the present health challenge due to antimicrobial resistance.