- α-Amino Diphenyl Phosphonates as Novel Inhibitors of Escherichia coli ClpP Protease
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Increased Gram-negative bacteria resistance to antibiotics is becoming a global problem, and new classes of antibiotics with novel mechanisms of action are required. The caseinolytic protease subunit P (ClpP) is a serine protease conserved among bacteria that is considered as an interesting drug target. ClpP function is involved in protein turnover and homeostasis, stress response, and virulence among other processes. The focus of this study was to identify new inhibitors of Escherichia coli ClpP and to understand their mode of action. A focused library of serine protease inhibitors based on diaryl phosphonate warheads was tested for ClpP inhibition, and a chemical exploration around the hit compounds was conducted. Altogether, 14 new potent inhibitors of E. coli ClpP were identified. Compounds 85 and 92 emerged as most interesting compounds from this study due to their potency and, respectively, to its moderate but consistent antibacterial properties as well as the favorable cytotoxicity profile.
- Moreno-Cinos, Carlos,Sassetti, Elisa,Salado, Irene G.,Witt, Gesa,Benramdane, Siham,Reinhardt, Laura,Cruz, Cristina D.,Joossens, Jurgen,Van Der Veken, Pieter,Br?tz-Oesterhelt, Heike,Tammela, P?ivi,Winterhalter, Mathias,Gribbon, Philip,Windshügel, Bj?rn,Augustyns, Koen
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p. 774 - 797
(2019/01/30)
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- Photoinduced electron transfer-promoted debenzylation of phenylalanine and tyrosine derivatives using dicyanoarene
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Photoinduced debenzylations of phenylalanine and tyrosine derivatives with dicyanoarenes afford glycine derivatives by the generation of radical cations. Despite the limited substrate scope, the radical cation of phenylalanine and tyrosine derivatives bearing both a carbamate (without an aromatic group) at the N-terminal and an amide at the C-terminal could promote the breaking C–C bond at the benzylic position by a photoinduced electron transfer. It is important to understand the chemical behavior of the radical cations of phenylalanine and tyrosine in enzymes involving electron transfer.
- Yamawaki, Mugen,Okita, Yoshiki,Yamamoto, Takashi,Morita, Toshio,Yoshimi, Yasuharu
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p. 7239 - 7244
(2017/11/20)
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- A stereocontrolled synthesis of a new class of 3,4,5,6- tetrahydropyrimidine-based chiral amino acids
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The stereocontrolled synthesis of seven 2-substituted-4-carboxy-3,4,5,6- tetrahydropyrimidines bearing either one chiral center at C-4 or two chiral centers at C-4 and C-8 was performed by condensation of (S)- or (R)- 2,4- diaminobutyric acid (Daba) with iminoethers derived from glycine, (S)- and (R)- serine, (S)- and (R)- tyrosine. Under the conditions reported, epimerization was always completely prevented at the C-4 center, whereas at the C-8 center, it was completely avoided in the case of tyrosine derivatives and considerably diminished for the serine derivatives.
- Zamri, Adel,Sirockin, Finton,Abdallah, Mohamed A.
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p. 5157 - 5170
(2007/10/03)
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- Anti-atherosclerotic aryl compounds
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The present invention is concerned with compounds of formula (I) STR1 wherein Ar is a mono- or bicyclic aromatic group optionally containing one or two heteroatoms independently selected from nitrogen, oxygen and sulphur, said group being optionally subst
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