om201146c_si_002.cif (75.93 kB)
Sandwich and Half-Sandwich Derivatives of Platensimycin: Synthesis and Biological Evaluation
dataset
posted on 2012-08-27, 00:00 authored by Malay Patra, Gilles Gasser, Michaela Wenzel, Klaus Merz, Julia E. Bandow, Nils Metzler-NolteThe multistep synthesis and biological evaluation of
five structurally
diverse, chiral and achiral CpMn(CO)3 (4, 7 and 8), (η6-arene)Cr(CO)3 (5), and [3]ferrocenophane-1-one (6) containing platensimycin (1) derivatives are described
in this report. The structures were inspired by the antibiotic platensimycin.
All the chiral compounds presented in this report are racemates.
The new compounds were unambiguously characterized by 1H and 13C NMR spectroscopy, mass spectrometry, IR spectroscopy,
and elemental analysis and in certain cases by X-ray crystallography
(4, 16, 18, and 29). The antibacterial and antitumor activity of selected derivatives
was tested. Molecular modeling suggests that the derivatives described
here may well fit into the active site of the FabF enzyme, which is
the biological target of platensimycin. Hence, the antimicrobial activities
of our new bioorganometallices 4–8 and the protected amide intermediates 15, 17, 18, 23, 28, 29, and 31 were tested against various Gram-positive and
Gram-negative bacterial strains. However, all compounds were inactive
up to concentrations of 180 μg/mL. The cytotoxicity of compounds 4 and 6 and the protected amide intermediates 15, 17, 18, 23, 28, 29, and 31 was tested against
HepG2 and PT45 mammalian cancer cell lines. Surprisingly, all compounds
containing a trimethylsilylethyl ester functionality at the aromatic
ring (17, 23, 29, and 31) displayed rather high cytotoxicity between 2 and 9 μM.
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Keywords
Molecular modelingFabF enzymederivativeBiological EvaluationThe multistep synthesischiral compoundstrimethylsilylethyl ester functionalitymass spectrometryantitumor activityIR spectroscopyintermediateantibiotic platensimycincompounds 41 Hamide13 C NMR spectroscopyantimicrobial activitiescancer cell lines9 μ MPT 45cytotoxicityHepG 2
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