Octadecanoyl-L-homoserine lactone

N-acyl homoserine lactones are bacterial signalling molecules involved in regulating diverse metabolic functions, particularly those relating to virulence, in concert with cell density. Each aspect of the signalling pathway, from production and recognition of the signal to expression of the target genes, offers a potential opportunity for exploitation. Attention is now focusing on the development of novel methods for bacterial enumeration, modulation of bacterial virulence and flexible, coordinated expression of heterologous genes through the use of N-acyl-homoserine-lactone-based systems.

The sesquiterpene γ-lactone estafiatin1, the molecule of which has a structure of 3,4α-epoxy-1,5,7α,6β(H)-guai-10(14),11(13)-dien-6,12-olide, is characteristic of plants of the generaAchilleaL. andArtemisiaL. of theAsteraceaefamily. This article presents the results of chemical modification for three reaction centers of the estafiatin molecule1: epoxy cycle, exomethylene group conjugated with γ-lactone carbonyl, and exomethylene group in position C10=C14; and at the same time 33 new derivatives were synthesized, the structures of which were established based on physicochemical constants, spectral data (IR-, PMR-,13C-NMR), and X-ray diffraction analysis. The stereo- and regiospecificity, as well as the chemoselectivity of the reaction based on estafiatin molecule1, are discussed. The reactivity of the substrate is significantly influenced by the stereochemistry of its molecule, the nature of the reagent, and the reaction medium. Based on the results of in silico screening, derivatives of estafiatin with high binding energies for both DNA-topoisomerase I and DNA-topoisomerase II were identified. The values of the inhibitory dose of IC50for estafiatin1and its derivatives were determined on cell lines of eight types of tumors.in vivoexperiments of the samples made it possible to establish that estafiatin1and its derivatives have pronounced antitumor activity against Pliss lymphosarcoma, Walker's carcinosarcoma, sarcoma 45, sarcoma-180, alveolar liver cancer PC-1, leukemia P-388 and L-1210, and sarcoma-45 resistant to 5-fluorouracil.

The cell-to-cell communication of microorganisms is known to be via exertion of certain chemical compounds (signal molecules) and is referred to as quorum sensing (QS). QS phenomenon is widespread in microbial communities. Several Gram-positive and Gram-negative bacteria and fungi use lactone-containing compounds (e.g. acyl-homoserine lactones (AHLs), γ-heptalactone, butyrolactone-I) as signalling molecules. The ability of microorganisms to metabolise these compounds and the mechanisms they employ for this purpose are not clearly understood. Many studies, however, have focused on identifying AHL and other lactone-degrading enzymes produced by bacteria and fungi. Various strains that are able to utilise these signalling molecules as carbon and energy sources have also been isolated. In addition, several reports have provided evidence on the involvement of lactones and lactone-degrading enzymes in numerous biological functions. These studies, although focused on processes other than metabolism of lactone signalling molecules, still provide insights into further understanding of the mechanisms employed by various microorganisms to metabolise the QS compounds. In this review, we consider conceivable microbial strategies to metabolise AHL and other lactone-containing signalling molecules such as γ-heptalactones.