Sandwich and Half-Sandwich Derivatives of Platensimycin: Synthesis and Biological Evaluation

Abstract

The multistep synthesis and biological evaluation of five structurally diverse, chiral and achiral CpMn(CO) 3 (4, 7 and 8), (η 6 -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 1 H and 13 C 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.

Ferrocenyl Derivatives of the Anthelmintic Praziquantel: Design, Synthesis, and Biological Evaluation

“…[13][14][15][16][17][18][19][20][21][22][23][24][25][26] This strategy was found very successful with ferroquine (FQ), a ferrocenyl analogue of the antimalarial drug chloroquine (CQ), as FQ is active on CQ-resistant Plasmodium falciparum strains. Furthermore, intensive chemical biology studies have recently allowed unveiling additional modes of action for FQ compared to the parent drug in FQ, which were attributed to the presence of the organometallic unit.…”

Synthesis and anodic electrochemistry of cymanquine and related complexes

“…Although a ferrocenyl group has been the most frequently-utilized OM conjugate [6], other moieties are being increasingly investigated, especially for the purpose of employing metalcarbonyl IR absorptions as analytical markers [7,8]. Among the most promising non-ferrocenyl OM bioconjugates are the strongly IR-active Group 7 'piano-stool' moieties M(CO) 3 (η 5 -C 5 H 4 R), which have been termed cymantrene and cyrhetrene, when M = Mn and M = Re, respectively, and R = H [9][10][11][12][13][14][15][16].…”

Theoretical Insight into the Medicinal World of Organometallics: Macro versus Nano

“…Metal NHC complexes are also having pharmacological properties as novel antibacterial and antitumor drugs. Their mode of action is both coordinated metal-respective biological target-dependent thioredoxin reductase or other enzymes containing (seleno) cysteine residues in their active site for gold or DNA for copper NHC complexes (half-sandwich) [60,32], ruthenium [27], or manganese [28,61] bioorganometallic species and complex containing an acetylsalicylic acid (aspirin) derived ligand emerged as cytotoxic drugs.…”