- Identification and Structure-Activity Relationships of Novel Compounds that Potentiate the Activities of Antibiotics in Escherichia coli
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In Gram-negative bacteria, efflux pumps are able to prevent effective cellular concentrations from being achieved for a number of antibiotics. Small molecule adjuvants that act as efflux pump inhibitors (EPIs) have the potential to reinvigorate existing antibiotics that are currently ineffective due to efflux mechanisms. Through a combination of rigorous experimental screening and in silico virtual screening, we recently identified novel classes of EPIs that interact with the membrane fusion protein AcrA, a critical component of the AcrAB-TolC efflux pump in Escherichia coli. Herein, we present initial optimization efforts and structure-activity relationships around one of those previously described hits, NSC 60339 (1). From these efforts we identified two compounds, SLUPP-225 (17h) and SLUPP-417 (17o), which demonstrate favorable properties as potential EPIs in E. coli cells including the ability to penetrate the outer membrane, improved inhibition of efflux relative to 1, and potentiation of the activity of novobiocin and erythromycin.
- Haynes, Keith M.,Abdali, Narges,Jhawar, Varsha,Zgurskaya, Helen I.,Parks, Jerry M.,Green, Adam T.,Baudry, Jerome,Rybenkov, Valentin V.,Smith, Jeremy C.,Walker, John K.
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p. 6205 - 6219
(2017/08/02)
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- A novel nickel-catalyzed synthesis of thioesters, esters and amides from aryl iodides in the presence of chromium hexacarbonyl
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This study describes our findings on a novel and cheap NiCl2 catalytic system under ligand-free conditions for the efficient thiocarbonylation, alkoxycarbonylation and amidocarbonylation reactions of aryl iodides in the presence of Cr(CO)6 as the solid source of carbon monoxide under air. A variety of aryl iodides tolerated the reaction conditions and structurally different thiols, alcohols and amines were used efficiently. The corresponding thioesters, esters and amides were obtained in good to excellent yield at atmospheric pressure under mild reaction conditions.
- Iranpoor, Nasser,Firouzabadi, Habib,Etemadi-Davan, Elham,Nematollahi, Arash,Firouzi, Hamid Reza
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p. 6445 - 6452
(2015/08/11)
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- An efficient N-heterocyclic carbene based ruthenium-catalyst: Application towards the synthesis of esters and amides
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A highly stable benzimidazolylidene based N-heterocyclic carbene (NHC) ruthenium catalyst was prepared starting with readily accessible starting materials. Under inert gas atmosphere and in air the catalyst showed high activity for the direct synthesis of esters from primary alcohols and of amides from primary alcohols and amines. Di-, tri-, and oligo-amides were obtained by using specific starting materials.
- Malineni, Jagadeesh,Merkens, Carina,Keul, Helmut,M?ller, Martin
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- Efficient microwave access to polysubstituted amidines from imidoylbenzotriazoles
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Microwave reactions of primary and secondary amines with imidoylbenzotriazoles 6a-w gave diversely substituted amidines 7a-Aa in 76-94% yields. Convenient preparations of a variety of amides 5a-Ab (87-96%) and imidoylbenzotriazoles 6a-w (56-95%) have also been developed using microwave irradiation under mild conditions and short reaction times. These results demonstrate further the advantages of microwave synthesis and introduce a new application of imidoylbenzotriazoles in the preparation of polysubstituted amidines.
- Katritzky, Alan R.,Cai, Chunming,Singh, Sandeep K.
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p. 3375 - 3380
(2007/10/03)
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- [10]Paracyclophanediamides and their octadehydro derivatives: Novel exotopic receptors with hydrogen-bonding sites on the bridge
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2,9-Diaza-1,10-dioxo[10]paracyclophanes were prepared in short steps from the terephthaloyl chlorides via the corresponding 4,6-diyne derivatives, and the amide groups on the bridge endow the skeleton with the guest-binding properties as demonstrated by c
- Katoono, Ryo,Kawai, Hidetoshi,Fujiwara, Kenshu,Suzuki, Takanori
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p. 8455 - 8459
(2007/10/03)
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