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| 2. |
- Mojica, Sergio A., et al.
(författare)
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N-acylated derivatives of sulfamethoxazole block Chlamydia fatty acid synthesis and interact with FabF
- 2017
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Ingår i: Antimicrobial Agents and Chemotherapy. - : American society for microbiology. - 0066-4804 .- 1098-6596. ; 61:10
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Tidskriftsartikel (refereegranskat)abstract
- The type II fatty acid synthesis (FASII) pathway is essential for bacterial lipid biosynthesis and continues to be a promising target for novel antibacterial compounds. Recently, it has been demonstrated that Chlamydia is capable of FASII and this pathway is indispensable for Chlamydia growth. Previously, a high-content screen with Chlamydia trachomatis-infected cells was performed, and acylated sulfonamides were identified to be potent growth inhibitors of the bacteria. C. trachomatis strains resistant to acylated sulfonamides were isolated by serial passage of a wild-type strain in the presence of low compound concentrations. Results from whole-genome sequencing of 10 isolates from two independent drug-resistant populations revealed that mutations that accumulated in fabF were predominant. Studies of the interaction between the FabF protein and small molecules showed that acylated sulfonamides directly bind to recombinant FabF in vitro and treatment of C. trachomatis-infected HeLa cells with the compounds leads to a decrease in the synthesis of Chlamydia fatty acids. This work demonstrates the importance of FASII for Chlamydia development and may lead to the development of new antimicrobials.
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| 3. |
- Sunduru, Naresh, et al.
(författare)
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Design, synthesis and evaluation of novel polypharmacological antichlamydial agents
- 2015
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Ingår i: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 101, s. 595-603
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Tidskriftsartikel (refereegranskat)abstract
- Discovery of new polypharmacological antibacterial agents with multiple modes of actions can be an alternative to combination therapy and also a possibility to slow development of antibiotic resistance. In support to this hypothesis, we synthesized 16 compounds by combining the pharmacophores of Chlamydia trachomatis inhibitors and inhibitors of type III secretion (T3S) in gram-negative bacteria. In this study we have developed salicylidene acylhydrazide sulfonamides (11c & 11d) as new antichlamydial agents that also inhibit T3S in Yersinia pseudotuberculosis.
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| 4. |
- Sunduru, Naresh, et al.
(författare)
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N-aryl 2-aryloxyacetamides as a new class of fatty acid amide hydrolase (FAAH) inhibitors
- 2017
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Ingår i: Journal of enzyme inhibition and medicinal chemistry (Print). - : Informa UK Limited. - 1475-6366 .- 1475-6374. ; 32:1, s. 513-521
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Tidskriftsartikel (refereegranskat)abstract
- Fatty acid amide hydrolase (FAAH) is a promising target for the development of drugs to treat neurological diseases. In search of new FAAH inhibitors, we identified 2-(4-cyclohexylphenoxy)-N-(3-(oxazolo[4,5-b] pyri-din-2-yl) phenyl) acetamide, 4g, with an IC50 of 2.6 mu M as a chemical starting point for the development of potent FAAH inhibitors. Preliminary hit-to-lead optimisation resulted in 2-(4-phenylphenoxy)-N-(3-(oxazolo[4,5-b] pyridin-2-yl)phenyl) acetamide, 4i, with an IC50 of 0.35 mu M.
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