Design, synthesis and biological evaluation of α-substituted isonipecotic acid benzothiazole analogues as potent bacterial type II topoisomerase inhibitors

Axford, Lorraine C.; Agarwal, Piyush K.; Anderson, Kelly H.; Andrau, Laura; Atherall, John; Barker, Stephanie; Bennett, James M.; Blair, Michael; Collins, Ian; Czaplewski, Lloyd G.; Davies, David T.; Gannon, Carlie T.; Kumar, Dushyant; Lancett, Paul; Logan, Alastair; Lunniss, Christopher J.; Mitchell, Dale R.; Offermann, Daniel A.; Palmer, James T.; Palmer, Norman D.; Pitt, Gary R. W.; Pommier, Stéphanie; Price, Daniel J.; Rao, Bhaskara; Saxena, Rashmi; Shukla, Tarun; Singh, Amit Kumar; Singh, Mahipal; Srivastava, A. K.; Steele, Christopher; Stokes, Neil R.; Thomaides-Brears, Helena; Tyndall, Edward M.; Watson, David E.; Haydon, David J.

doi:10.1016/j.bmcl.2013.10.058

Cited by 33 publications

(22 citation statements)

References 4 publications

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Section: Dna Gyrase and Topoisomerase IV Inhibitorsmentioning

confidence: 99%

“…It was observed that the presence of a cyclic amine between the carboxylate and the C-5 aryl group enhanced the antibacterial activity and the solubility compared to the derivatives without this group. 23 Further improvement in the PK profile was obtained with the inclusion of an α substituent to the carboxylic acid, which showed enhanced solubility, excellent oral bioavailability, and lower clearance. Remarkably, compounds 3a,b had powerful inhibitory activity against S. aureus topoisomerase IV (0.012 and 0.008 μg/mL, respectively), proving their selectivity toward the bacterial isoform without affecting human topoisomerase II.…”

Section: Dna Gyrase and Topoisomerase IVmentioning

confidence: 99%

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Thiazoles, Their Benzofused Systems, and Thiazolidinone Derivatives: Versatile and Promising Tools to Combat Antibiotic Resistance

et al. 2020

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Thiazoles, their benzofused systems, and thiazolidinone derivatives are widely recognized as nuclei of great value for obtaining molecules with various biological activities, including analgesic, anti-inflammatory, anti-HIV, antidiabetic, antitumor, and antimicrobial. In particular, in the past decade, many compounds bearing these heterocycles have been studied for their promising antibacterial properties due to their action on different microbial targets. Here we assess the recent development of this class of compounds to address mechanisms underlying antibiotic resistance at both bacterial-cell and community levels (biofilms). We also explore the SAR and the prospective clinical application of thiazole and its benzofused derivatives, which act as inhibitors of mechanisms underlying antibiotic resistance in the treatment of severe drug-resistant infections. In addition, we examined all bacterial targets involved in their antimicrobial activity reporting, when described, their spontaneous frequencies of resistance.

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Section: Dna Gyrase and Topoisomerase IV Inhibitorsmentioning

confidence: 99%

Section: Dna Gyrase and Topoisomerase IVmentioning

confidence: 99%

Thiazoles, Their Benzofused Systems, and Thiazolidinone Derivatives: Versatile and Promising Tools to Combat Antibiotic Resistance

et al. 2020

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“…Moreover, the benzothiazole core is a widespread scaffold that has been extensively studied [ 54 , 55 , 56 , 57 , 58 , 59 ] and many derivatives are found to be antimicrobial [ 49 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 ], anticancer [ 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 ], anti-Alzheimer’s [ 92 , 93 ], anti-inflammatory [ 94 , 95 , 96 ], anti-HIV [ 97 , 98 , 99 ] anticonvulsant [ 100 , 101 , 102 ], antioxidant [ 39 , 103 ], anti-tuberculosis [ 104 ...…”

Section: Benzazolesmentioning

confidence: 99%

Importance of Fluorine in Benzazole Compounds

2020

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Fluorine-containing heterocycles continue to receive considerable attention due to their unique properties. In medicinal chemistry, the incorporation of fluorine in small molecules imparts a significant enhancement their biological activities compared to non-fluorinated molecules. In this short review, we will highlight the importance of incorporating fluorine as a basic appendage in benzothiazole and benzimidazole skeletons. The chemistry and pharmacological activities of heterocycles containing fluorine during the past years are compiled and discussed.

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“…Moreover no cross-resistance was observed caused by the mechanisms responsible for conferring resistance to these antibiotics. Both compounds also showed promising pharmacokinetic profile in rat and mouse [80]. gonorrhoeae.…”

Section: Gyrb and Pare Dual Inhibitorsmentioning

confidence: 88%

Dual targeting DNA gyrase B (GyrB) and topoisomerse IV (ParE) inhibitors: A review

Azam

Thathan

Selvaraj

2015

Bioorganic Chemistry

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Design, synthesis and biological evaluation of α-substituted isonipecotic acid benzothiazole analogues as potent bacterial type II topoisomerase inhibitors

Cited by 33 publications

References 4 publications

Thiazoles, Their Benzofused Systems, and Thiazolidinone Derivatives: Versatile and Promising Tools to Combat Antibiotic Resistance

Thiazoles, Their Benzofused Systems, and Thiazolidinone Derivatives: Versatile and Promising Tools to Combat Antibiotic Resistance

Importance of Fluorine in Benzazole Compounds

Dual targeting DNA gyrase B (GyrB) and topoisomerse IV (ParE) inhibitors: A review

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