New Thiazole Nortopsentin Analogues Inhibit Bacterial Biofilm Formation

Abstract

New thiazole nortopsentin analogues were conveniently synthesized and evaluated for their activity as inhibitors of biofilm formation of relevant Gram-positive and Gram-negative pathogens. All compounds were able to interfere with the first step of biofilm formation in a dose-dependent manner, showing a selectivity against the staphylococcal strains. The most active derivatives elicited IC50 values against Staphylococcus aureus ATCC 25923, ranging from 0.40–2.03 µM. The new compounds showed a typical anti-virulence profile, being able to inhibit the biofilm formation without affecting the microbial growth in the planktonic form.

3-(6-Phenylimidazo [2,1-b][1,3,4]thiadiazol-2-yl)-1H-Indole Derivatives as New Anticancer Agents in the Treatment of Pancreatic Ductal Adenocarcinoma

“…Analytical and spectroscopic data for compounds 5a,b are in agreement with those reported in literature [40].…”

Role of Indole Scaffolds as Pharmacophores in the Development of Anti-Lung Cancer Agents

“…The most prominent and widely used ones are those reported by Fisher [8], Bischler [9], Hemetsberger [10], Nenitzescu [11], Bartoli [12], and others [13,14]. Owing to its bioavailability and pharmacological applications, indole is considered the most privileged scaffold in heterocyclic chemistry with such widespread applications as antiviral, antimicrobial, anti-inflammatory, anti-cancer, anti-hypertensive, anti-diabetic, and antioxidant [15][16][17].…”

“…Zafirlukast is the first orally active indolelike leukotriene-receptor antagonist approved by the FDA to treat asthma ( Figure 3) [27]. It is mostly Owing to its bioavailability and pharmacological applications, indole is considered the most privileged scaffold in heterocyclic chemistry with such widespread applications as antiviral, antimicrobial, anti-inflammatory, anti-cancer, anti-hypertensive, anti-diabetic, and antioxidant [15][16][17].…”

“…It was theorized that the fluorinated indole (17) plays an important role in enhancing the binding interaction with T790M active binding domain of EGFR and reducing the demethylation ability of the indole ring, which in turn, can enhance the anti-metabolism ability of AZD9291 derivatives. The fluorinated derivative of AZD9291 (17), however, resulted in the loss of kinase activity. Next, the authors designed compound 16b by the aid of molecular docking studies to obtain an optimized derivative without fluorine substitution.…”

“…A structure-activity relationship study of AZD9291 reported by Zhao et al showed that the fluorinated analog (17, Figure 6) improved selectivity towards EGFRT 790M/L858R double mutants with IC 50 as low as 8 nM and a 200-fold increase in the selectivity towards wild type EGFR. It was theorized that the fluorinated indole (17) plays an important role in enhancing the binding interaction with T790M active binding domain of EGFR and reducing the demethylation ability of the indole ring, which in turn, can enhance the anti-metabolism ability of AZD9291 derivatives. The fluorinated derivative of AZD9291 (17), however, resulted in the loss of kinase activity.…”