Effect of dexamethasone and tenoxicam on the virulence activities of different clinical isolates.

Introduction: This study aimed to examine the effect of commonly used non-antibiotic drugs (dexamethasone and tenoxicam), on treatment of infections, antibiotic resistance and virulence in this pathogen.

Methods: Four antibiotics (gentamicin, cefepime, ciprofloxacin and meropenem) were investigated. The proteolysis and hemolysis were selected as virulence factors for investigation.

Blood pH and COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic is a worldwide war. Raising the blood pH might be a crucial strategy to chase COVID-19. The human blood is slightly alkaline, which is essential for cell metabolism, normal physiology, and balanced immunity since all of these biological processes are pH-dependent.

Synthesis and in vitro antibacterial, antifungal, anti-proliferative activities of novel adamantane-containing thiazole compounds.

A series of (Z)-N-(adamantan-1-yl)-3,4-diarylthiazol-2(3H)-imines (5a-r) was synthesized via condensation of 1-(adamantan-1-yl)-3-arylthioureas (3a-c) with various aryl bromomethyl ketones (4a-f). The structures of the synthesized compounds were characterized by H NMR, C NMR and by X-ray crystallography. The in vitro inhibitory activities of the synthesized compounds were assessed against a panel of Gram-positive and Gram-negative bacteria, and pathogenic fungi.

Antimicrobial efficacy of extracts of Saudi Arabian desert truffles.

Background: truffles are known for their nutritional value and have been considered among traditional treatments for ophthalmic infections and ailments.

Objectives: We sought to investigate the antimicrobial efficacy of several extracts from Saudi Arabia. Certain pathogenic fungi and gram-negative and gram-positive bacteria were included.

The rational design, synthesis, and antimicrobial investigation of 2-Amino-4-Methylthiazole analogues inhibitors of GlcN-6-P synthase.

A series of novel 2-Amino-4-Methylthiazole analogs were developed via three-step reaction encompassing hydrazine-1-carboximidamide motif to combat Gram-positive and Gram-negative bacterial and fungal infections. Noticeably, the thiazole-carboximidamide derivatives 4a-d displayed excellent antimicrobial activity and the most efficacious analogue 4d with MIC/MBC values of 0.5 and 4 μg/mL, compared to reference drugs with very low toxicity to mammalian cells, resulting in a prominent selectivity more than 100 folds.

Antibacterial, antibiofilm and molecular modeling study of some antitumor thiazole based chalcones as a new class of DHFR inhibitors.

Some synthesized antitumor derivatives of thiazole based chalcones including thiazolo[2,3-b]quinazoline and pyrido[4,3-d]thiazolo[3,2-a]pyrimidine analogues were subjected to be tested against standard microbial strains. Compound 18 showed higher activity against both Gram-positive and Gram-negative bacteria with MIC of 1.0, 1.

Biotechnological applications of quorum sensing inhibition as novel therapeutic strategies for multidrug resistant pathogens.

High incidence of antibiotic resistance among bacterial clinical isolates necessitates the discovery of new targets for inhibition of microbial pathogenicity, without stimulation of microbial resistance. This could be achieved by targeting virulence determinants, which cause host damage and disease. Many pathogenic bacteria elaborate signaling molecules for cellular communication.

Design, Synthesis, Antimicrobial and Anti-biofilm Evaluation, and Molecular Docking of Newly Substituted Fluoroquinazolinones.

Background: Quinazolines and quinazolinones derivatives are well known for their important range of therapeutic activities.

Objective: The study aims to carry out the synthesis of some derivatives of substituted fluoroquinazolinones based on structure-based design and evaluation of their antibacterial, antifungal, and anti-biofilm activities.

Methods: Compounds were chemically synthesized by conventional methods.

Synthesis, Biological Evaluation, and Molecular Docking of Novel Thiazoles and [1,3,4]Thiadiazoles Incorporating Sulfonamide Group as DHFR Inhibitors.

2-(1-{4-[(4-Methylphenyl)sulfonamido]phenyl}ethylidene)thiosemicarbazide (3) was exploited as a starting material for the synthesis of two novel series of 5-arylazo-2-hydrazonothiazoles 6a - 6j and 2-hydrazono[1,3,4]thiadiazoles 10a - 10d, incorporating sulfonamide group, through its reactions with appropriate hydrazonoyl halides. The structures of the newly synthesized products were confirmed by spectral and elemental analyses. Also, the antimicrobial, anticancer, and DHFR inhibition potency for two series of thiazoles and [1,3,4]thiadiazoles were evaluated and explained by molecular docking studies and SAR analysis.

Synthesis, antimicrobial, anti-biofilm evaluation, and molecular modelling study of new chalcone linked amines derivatives.

A series of amide chalcones conjugated with different secondary amines were synthesised and characterised by different spectroscopic techniques H NMR, C NMR, and ESI-MS. They were screened for in vitro antibacterial activity. Compounds 36, 37, 38, 42, and 44 are the most active among the synthesised series exhibiting MIC value of 2.

Dual effect biodegradable ciprofloxacin loaded implantable matrices for osteomyelitis: controlled release and osteointegration.

Ciprofloxacin biodegradable implantable matrices (CPX-IMs) of tailored porous surfaces were fabricated by hot melt injection molding of poly-l-lactic acid (PLLA) followed by coating with PLLA/sodium chloride. CPX-IDs were designed to have a non-porous coat (NPC) or a porous coat of small pore size (SPC; 150-250 µm) or a large pore size (LPC; 250-350 µm). CPX-IMs surface pore size was confirmed by scanning electron microscope.

Quorum sensing inhibitory activity of sub-inhibitory concentrations of β-lactams.

Introduction: The virulence factors of are under the control of quorum sensing (QS) signals. Hence, interference with QS prevents its pathogenesis.

Objective: The aim of the present research is to assess the influence of some β-lactam antibiotics on cell communication and the release of different virulence factors.

Synthesis, biological evaluation and molecular modeling study of some new methoxylated 2-benzylthio-quinazoline-4(3H)-ones as nonclassical antifolates.

A new series of 2,3,6-substituted-quinazolin-4-ones was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, and antitumor activities. Compounds 28 and 61 proved to be active DHFR inhibitors with IC50 0.02 and 0.

Synthesis, biological evaluation and molecular modeling study of 2-(1,3,4-thiadiazolyl-thio and 4-methyl-thiazolyl-thio)-quinazolin-4-ones as a new class of DHFR inhibitors.

A new series of 2-(1,3,4-thiadiazolyl- or 4-methyl-thiazolyl)thio-6-substituted-quinazolin-4-one analogs was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, and antitumor activities. Compounds 29, 34, and 39 proved to be the most active DHFR inhibitors with IC50 values range of 0.1-0.

Nonclassical antifolates, part 4. 5-(2-aminothiazol-4-yl)-4-phenyl-4H-1,2,4-triazole-3-thiols as a new class of DHFR inhibitors: synthesis, biological evaluation and molecular modeling study.

A new series of compounds possessing 5-(2-aminothiazol-4-yl)-4-phenyl-4H-1,2,4-triazole-3-thiol skeleton was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, antitumor and schistosomicidal activities. Four active compounds were allocated, the antibacterial 22 (comparable to gentamicin and ciprofloxacin), the schistosomicidal 29 (comparable to praziquantel), the DHFR inhibitor 34 (IC₅₀ 0.03 μM, 2.

Nonclassical antifolates, part 3: synthesis, biological evaluation and molecular modeling study of some new 2-heteroarylthio-quinazolin-4-ones.

A new series of 2-heteroarylthio-6-substituted-quinazolin-4-one analogs was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, and antitumor activities. Compounds 21, 25, and 39 proved to be active DHFR inhibitors with IC50 range of 0.3-0.

Bacterial artificial chromosome clones of viruses comprising the towne cytomegalovirus vaccine.

Bacterial artificial chromosome (BAC) clones have proven invaluable for genetic manipulation of herpesvirus genomes. BAC cloning can also be useful for capturing representative genomes that comprise a viral stock or mixture. The Towne live attenuated cytomegalovirus vaccine was developed in the 1970s by serial passage in cultured fibroblasts.

Peptides from cytomegalovirus UL130 and UL131 proteins induce high titer antibodies that block viral entry into mucosal epithelial cells.

Cytomegalovirus infections are an important cause of disease for which no licensed vaccine exists. Recent studies have focused on the gH/gL/UL128-131 complex as antibodies to gH/gL/UL128-131 neutralize viral entry into epithelial cells. Prior studies have used cells from the retinal pigment epithelium, while to prevent transmission, vaccine-induced antibodies may need to block viral infection of epithelial cells of the oral or genital mucosa.

Non-classical antifolates. Part 2: synthesis, biological evaluation, and molecular modeling study of some new 2,6-substituted-quinazolin-4-ones.

A new series of 2,6-substituted-quinazolin-4-ones was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, and antitumor activities. Compounds 22, 33-37, 39-43, and 45 proved to be active DHFR inhibitors with IC(50) range of 0.4-1.

Involvement of transposon-like elements in penicillin gene cluster regulation.

Subtelomeric secondary metabolite (SM) gene clusters are frequently surrounded by DNA repeats and transposon-like elements. The Aspergillus nidulans penicillin cluster, 30kb from the telomere of chromosome VI, is bordered by such elements. Deletions of penicillin telomere proximal and distal border regions resulted in decreased penicillin production.

Biosynthetic origin of hygromycin A.

Hygromycin A, an antibiotic produced by Streptomyces hygroscopicus, is an inhibitor of bacterial ribosomal peptidyl transferase. The antibiotic binds to the ribosome in a distinct but overlapping manner with other antibiotics and offers a different template for generation of new agents effective against multidrug-resistant pathogens. Reported herein are the results from a series of stable-isotope-incorporation studies demonstrating the biosynthetic origins of the three distinct structural moieties which comprise hygromycin A.