{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T22:56:15Z","timestamp":1791068175306,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2009,9,25]],"date-time":"2009-09-25T00:00:00Z","timestamp":1253836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2009,11,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>The recent discovery of the natural product platensimycin as a new antibiotic lead structure has triggered the synthesis of numerous organic derivatives for structure\u2013activity relationship studies. Herein, we describe the synthesis, characterization and biological evaluation of the first organometallic antibiotic inspired by platensimycin. Two bioorganometallic compounds containing (\u03b7<jats:sup>6<\/jats:sup>\u2010pentamethylbenzene)Cr(CO)<jats:sub>3<\/jats:sub> (<jats:bold>2<\/jats:bold>) and (\u03b7<jats:sup>6<\/jats:sup>\u2010benzene)Cr(CO)<jats:sub>3<\/jats:sub> (<jats:bold>3<\/jats:bold>), linked by an amide bond to the aromatic part of platensimycin, were synthesized. Their antibiotic activities were tested against<\/jats:italic> B.\u2005subtilis <jats:italic>168 (Gram positive) and<\/jats:italic> E.\u2005coli <jats:italic>W3110 (Gram negative) bacterial strains. Both compounds were found to be inactive against<\/jats:italic> E.\u2005coli <jats:italic>but derivative <jats:bold>2<\/jats:bold> inhibits<\/jats:italic> B.\u2005subtilis <jats:italic>growth at a moderate MIC value of 0.15\u2005m<jats:sc>M<\/jats:sc>. To test the intrinsic toxicity of chromium, several chromium salts along with {\u03b7<jats:sup>6<\/jats:sup>\u2010(3\u2010pentamethylphenyl propionic acid)}Cr(CO)<jats:sub>3<\/jats:sub> (<jats:bold>5<\/jats:bold>) and {\u03b7<jats:sup>6<\/jats:sup>\u2010(3\u2010phenyl propionic acid)}Cr(CO)<jats:sub>3<\/jats:sub> (<jats:bold>6<\/jats:bold>) were tested against both bacterial strains. No activity was observed against<\/jats:italic> E.\u2005coli <jats:italic>for any of the compounds;<\/jats:italic> B.\u2005subtilis <jats:italic>growth was not inhibited by Cr(NO<jats:sub>3<\/jats:sub>)<jats:sub>3<\/jats:sub> and only very weakly by <jats:bold>5<\/jats:bold>, K<jats:sub>2<\/jats:sub>Cr<jats:sub>2<\/jats:sub>O<jats:sub>7<\/jats:sub> and Na<jats:sub>2<\/jats:sub>CrO<jats:sub>4<\/jats:sub> at MIC values of 0.5, 0.68 and 1.24\u2005m<jats:sc>M<\/jats:sc>, respectively. Compounds <jats:bold>2<\/jats:bold>, <jats:bold>3<\/jats:bold>, <jats:bold>5<\/jats:bold> and <jats:bold>4<\/jats:bold> (the pure organic analogue of <jats:bold>2<\/jats:bold>) show similar cytotoxicity against HeLa, HepG2 and HT\u201029 mammalian cell lines. Furthermore, the cellular uptake and the intracellular distribution of compounds <jats:bold>2<\/jats:bold>, <jats:bold>3<\/jats:bold> and Cr(NO<jats:sub>3<\/jats:sub>)<jats:sub>3<\/jats:sub> in<\/jats:italic> B.\u2005subtilis <jats:italic>were studied using atomic absorption spectroscopy to gain insight in to the possible cellular targets. Compound <jats:bold>2<\/jats:bold> was found to be readily taken up and distributed almost equally among cytosol, cell debris and cell membrane in<\/jats:italic> B.\u2005subtilis<jats:italic>.<\/jats:italic><\/jats:p>","DOI":"10.1002\/cmdc.200900347","type":"journal-article","created":{"date-parts":[[2009,9,25]],"date-time":"2009-09-25T14:09:08Z","timestamp":1253887748000},"page":"1930-1938","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Synthesis and Biological Evaluation of Chromium Bioorganometallics Based on the Antibiotic Platensimycin Lead Structure"],"prefix":"10.1002","volume":"4","author":[{"given":"Malay","family":"Patra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Gasser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Pinto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Merz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo","family":"Ott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia\u2005E.","family":"Bandow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Metzler\u2010Nolte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,10,23]]},"reference":[{"key":"e_1_2_6_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.200600145"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/431892a"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04784"},{"key":"e_1_2_6_4_2","doi-asserted-by":"crossref","first-page":"2582","DOI":"10.1002\/ange.200705303","volume":"120","author":"Tiefenbacher K.","year":"2008","journal-title":"Angew. 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Soc. Chim. Fr."},{"key":"e_1_2_6_40_2","unstructured":"Crystallographic data of14: C29H35CrNO10 M=609.58; monoclinic P21\/c a=8.342(2) b=57.10(1) c=12.676(4) b=95.662(9) V=6010(3)\u2005\u00c53 Z=8 R1=0.0918 for 6829 observed (I>2\u2009s) reflections andwR2=0.2309 for all 10\u2009205 reflections GOF=1.038 740 parameters. Bruker\u2010axs\u2010SMART 1000 CCD structure solution with direct methods (SHELXS97) and refined againstF2with all measured reflections (SHELXL97). Due to the long b axis the R1\u2010value of structure refinement converged by 0.0918. CCDC\u2005722266 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre viawww.ccdc.cam.ac.uk\/data_request\/cif."},{"key":"e_1_2_6_41_2","unstructured":"At this stage it should be noted that determination of a binding constant of2or4with the FabF enzyme was not possible as to the best of our knowledge no enzyme assay is currently commercially available or even published."},{"key":"e_1_2_6_42_2","unstructured":"Compound5could not be analyzed due to precipitation whenB.\u2005subtiliswas incubated with the compound at twice its MIC."},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200900185"},{"key":"e_1_2_6_43_3","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200900185"},{"key":"e_1_2_6_44_2","unstructured":"For new metal\u2010containing Platensimycin analogues a patent is pending (EP09154125)."},{"key":"e_1_2_6_45_2","unstructured":"G.\u2005M. Sheldrick inSHELXS\u201097 Program for Solution of Crystal Structures University of G\u00f6ttingen (Germany) 1997."},{"key":"e_1_2_6_46_2","unstructured":"G.\u2005M. Sheldrick inSHELXL\u201097 Program for Refinement of Crystal Structures University of G\u00f6ttingen (Germany) 1997."},{"key":"e_1_2_6_47_2","first-page":"34","volume":"46","author":"Spek A. L.","year":"1990","journal-title":"Acta Crystallogr. Sect. 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