Antibacterial activity evaluation and mode of action study of novel thiazole-quinolinium derivatives

Li, Ying; Sun, Ning; Ser, Hooi‐Leng; Long, Wei; Li, Yanan; Chen, Cuicui; Zheng, Bo-Xin; Huang, Xuan-He; Liu, Zhihua; Lu, Yu‐Jing

doi:10.1039/d0ra00691b

Cited by 27 publications

(9 citation statements)

References 40 publications

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“…The result suggested that among the synthesized compounds, 47a and 47b were the most potent and effective bacteriostatic agents against multi-drug resistant bacteria. In brief, the SAR study emphasized the requirements of small groups such as CH 3 or H at the 2-position of the quinoline fragment [91]. The novel methylthiazole-based thiazolidinones derivatives were synthesized when a solution of 2-amino-5-methylthiazole and sodium carbonate in anhydrous dimethylformamide (DMF) was added dropwise to a solution of chloroacetyl chloride in DMF, and the product obtained was exploited for multistep reactions to obtain the target compounds.…”

Section: Thiazoles As Antimicrobial Agentsmentioning

confidence: 99%

Thiazole: A Versatile Standalone Moiety Contributing to the Development of Various Drugs and Biologically Active Agents

Arshad¹,

Alam

Alshammari

et al. 2022

Molecules

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For many decades, the thiazole moiety has been an important heterocycle in the world of chemistry. The thiazole ring consists of sulfur and nitrogen in such a fashion that the pi (π) electrons are free to move from one bond to other bonds rendering aromatic ring properties. On account of its aromaticity, the ring has many reactive positions where donor–acceptor, nucleophilic, oxidation reactions, etc., may take place. Molecules containing a thiazole ring, when entering physiological systems, behave unpredictably and reset the system differently. These molecules may activate/stop the biochemical pathways and enzymes or stimulate/block the receptors in the biological systems. Therefore, medicinal chemists have been focusing their efforts on thiazole-bearing compounds in order to develop novel therapeutic agents for a variety of pathological conditions. This review attempts to inform the readers on three major classes of thiazole-bearing molecules: Thiazoles as treatment drugs, thiazoles in clinical trials, and thiazoles in preclinical and developmental stages. A compilation of preclinical and developmental thiazole-bearing molecules is presented, focusing on their brief synthetic description and preclinical studies relating to structure-based activity analysis. The authors expect that the current review may succeed in drawing the attention of medicinal chemists to finding new leads, which may later be translated into new drugs.

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Section: Thiazoles As Antimicrobial Agentsmentioning

confidence: 99%

Thiazole: A Versatile Standalone Moiety Contributing to the Development of Various Drugs and Biologically Active Agents

Arshad¹,

Alam

Alshammari

et al. 2022

Molecules

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“…From previous studies, it was clear that thiazole and quinolinium groups are important for antibacterial activity. Li et al synthesized various thiazole-quinolinium derivatives and evaluated their antibacterial activities against Gram positive and Gram negative species ( Li et al, 2015 ). All compounds showed good antibacterial activity (MIC 1–32 μg/mL) against S. aureus.…”

Section: Quinoline Ring Compoundsmentioning

confidence: 99%

Targeting the Achilles Heel of FtsZ: The Interdomain Cleft

Pradhan

Margolin²,

Beuria

2021

Front. Microbiol.

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Widespread antimicrobial resistance among bacterial pathogens is a serious threat to public health. Thus, identification of new targets and development of new antibacterial agents are urgently needed. Although cell division is a major driver of bacterial colonization and pathogenesis, its targeting with antibacterial compounds is still in its infancy. FtsZ, a bacterial cytoskeletal homolog of eukaryotic tubulin, plays a highly conserved and foundational role in cell division and has been the primary focus of research on small molecule cell division inhibitors. FtsZ contains two drug-binding pockets: the GTP binding site situated at the interface between polymeric subunits, and the inter-domain cleft (IDC), located between the N-terminal and C-terminal segments of the core globular domain of FtsZ. The majority of anti-FtsZ molecules bind to the IDC. Compounds that bind instead to the GTP binding site are much less useful as potential antimicrobial therapeutics because they are often cytotoxic to mammalian cells, due to the high sequence similarity between the GTP binding sites of FtsZ and tubulin. Fortunately, the IDC has much less sequence and structural similarity with tubulin, making it a better potential target for drugs that are less toxic to humans. Over the last decade, a large number of natural and synthetic IDC inhibitors have been identified. Here we outline the molecular structure of IDC in detail and discuss how it has become a crucial target for broad spectrum and species-specific antibacterial agents. We also outline the drugs that bind to the IDC and their modes of action.

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“…methylpiperidin-1-yl)propyl)benzo[d]thiazol-2(3H)-ylidene)methyl)quinolin-1-ium iodide was synthesized according to the procedures reported previously. 50 The compound was obtained as a dark brown solid with 62% yield. 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.14 (s, 0.79H), 8.71 (s, 1H), 8.19 (d, J = 8.5 Hz, 1H), 8.08 (d, J = 8.5 Hz, 1H), 8.01−7.98 (t, J = 7.7 Hz, 1H), 7.83 (d, J = 8.5 Hz, 2H), 7.75 (t, J = 7.7 Hz, 2H), 7.68 (s, 1H), 7.65−7.54 (m, 4H), 7.39 (t, J = 7.7 Hz, 1H), 6.93−6.86 (m, 3H), 4.64 (m, 2H), 4.17 (s, 3H), 2.14 (m, 2H), 1.75−1.57 (m, 3H), 1.22 (m, 6H), 0.88 (m, 5H).…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…quinolin-1-ium iodide was synthesized according to the procedures reported previously. 50 The compound was obtained as a dark brown solid with 63% yield. 1 UV−Visible and Fluorescence Assays.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Molecular Recognition and Imaging of Human Telomeric G-Quadruplex DNA in Live Cells: A Systematic Advancement of Thiazole Orange Scaffold To Enhance Binding Specificity and Inhibition of Gene Expression

et al. 2021

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A series of fluorescent ligands, which were systematically constructed from thiazole orange scaffold, was investigated for their interactions with G-quadruplex structures and antitumor activity. Among the ligands, compound 3 was identified to exhibit excellent specificity toward telomere G4-DNA over other nucleic acids. The affinity of 3-Htg24 was almost 5 times higher than that of double-stranded DNA and promoter G4-DNA. Interaction studies showed that 3 may bind to both G-tetrad and the lateral loop near the 5′-end. The intracellular colocalization with BG4 and competition studies with BRACO19 reveal that 3 may interact with G4-structures. Moreover, 3 reduces the telomere length and downregulates hTERC and hTERT mRNA expression in HeLa cells. The cytotoxicity of 3 against cancer cells (IC50 = 12.7–16.2 μM) was found to be generally higher than noncancer cells (IC50 = 52.3 μM). The findings may support that the ligand is telomere G4-DNA specific and may provide meaningful insights for anticancer drug design.

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Antibacterial activity evaluation and mode of action study of novel thiazole-quinolinium derivatives

Abstract: A new series of thiazole-quinolinium derivatives perturb the polymerization of FtsZ with strong antibacterial activities.

Cited by 27 publications

References 40 publications

Thiazole: A Versatile Standalone Moiety Contributing to the Development of Various Drugs and Biologically Active Agents

Thiazole: A Versatile Standalone Moiety Contributing to the Development of Various Drugs and Biologically Active Agents

Targeting the Achilles Heel of FtsZ: The Interdomain Cleft

Molecular Recognition and Imaging of Human Telomeric G-Quadruplex DNA in Live Cells: A Systematic Advancement of Thiazole Orange Scaffold To Enhance Binding Specificity and Inhibition of Gene Expression

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