The effect of minimum inhibitory concentrations (MICs) of six novel fenpropimorph derivatives on lipid and sterol composition of Candida albicans, Cryptococcus neoformans, Malassezia pachydermatis and Malassezia furfur was investigated. The MICs for the most effective derivatives were found in the range from 3.7 to 56.7 microM and were 2-3 times lower compared to the commercial fungicide bifonazol. The more efficient fenpropimorph derivatives were the piperidine derivative for C. albicans and the allylamine derivative for Cr. neoformans, M. pachydermatis and M. furfur. The inhibitor in the growth medium reduced the unsaturation index of the total lipid content in M. furfur and C. albicans.
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http://dx.doi.org/10.1515/znc-2001-1-210 | DOI Listing |
Molecules
November 2021
Department of Pharmacy-Center for Drug Research, Ludwig-Maximilians University Munich, 81377 Munich, Germany.
The aliphatic heterocycles piperidine and morpholine are core structures of well-known antifungals such as fenpropidin and fenpropimorph, commonly used as agrofungicides, and the related morpholine amorolfine is approved for the treatment of dermal mycoses in humans. Inspired by these lead structures, we describe here the synthesis and biological evaluation of 4-aminopiperidines as a novel chemotype of antifungals with remarkable antifungal activity. A library of more than 30 4-aminopiperidines was synthesized, starting from -substituted 4-piperidone derivatives by reductive amination with appropriate amines using sodium triacetoxyborohydride.
View Article and Find Full Text PDFReprod Toxicol
September 2020
Department for Innovative Testing Strategies, Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
Knowledge on mode-of-action (MOA) is required to understand toxicological effects of compounds, notably in the context of risk assessment of mixtures. Such information is generally scarce, and often complicated by the existence of multiple MOAs per compound. Here, MOAs related to developmental craniofacial malformations were derived from literature, and assembled in a MOA network.
View Article and Find Full Text PDFEnviron Health Perspect
January 2020
Department of Chemistry and Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee, USA.
Background: Changes in cholesterol metabolism are common hallmarks of neurodevelopmental pathologies. A diverse array of genetic disorders of cholesterol metabolism support this claim as do multiple lines of research that demonstrate chemical inhibition of cholesterol biosynthesis compromises neurodevelopment. Recent work has revealed that a number of commonly used pharmaceuticals induce changes in cholesterol metabolism that are similar to changes induced by genetic disorders with devastating neurodevelopmental deficiencies.
View Article and Find Full Text PDFIn accordance with Article 43 of Regulation (EC) 396/2005, EFSA received a request from the European Commission to provide support for the preparation of the EU position for 50th session of the Codex Committee on Pesticide Residues (CCPR). In 2017, Joint FAO/WHO Meeting on Pesticide Residues (JMPR) evaluated 15 active substances regarding the setting of toxicological reference values to be used in consumer risk assessment (bicyclopyrone, chlormequat, cyclaniliprole, fenazaquin, fenpropimorph, fenpyrazamine, fenpyroximate, fosetyl Al, isoprothiolane, natamycin, oxamyl, phosphonic acid, propylene oxide, thiophanate-methyl, triflumezopyrim) and 36 substances for deriving maximum residue limit (MRL) proposals (acetamiprid, azoxystrobin, bicyclopyrone, captan, chlormequat, cyclaniliprole, cyprodinil, 2,4-D, difenoconazole, fenazaquin, fenpropimorph, fenpyrazamine, fenpyroximate, flonicamid, fluensulfone, fluopyram, flupyradifurone, fosetyl Al, imazamox, imazapyr, imidacloprid, isoprothiolane, isopyrazam, natamycin, oxamyl, phosphonic acid, picoxystrobin, propiconazole, propylene oxide, prothioconazole, quinclorac, saflufenacil, spinetoram, tebuconazole, trifloxystrobin, triflumezopyrim); EFSA prepared comments on the Codex MRL proposals and the proposed toxicological reference values. In addition, EFSA provided the views on follow-up assessments of JMPR on pesticides where specific concerns were raised in the previous CCPR meetings.
View Article and Find Full Text PDFPLoS One
December 2018
INRA UMR 1331 Toxalim, University of Toulouse, INP, ENVT, EIP, UPS, UMR1331, Toulouse, France.
The use of pesticides exposes humans to numerous harmful molecules. Exposure in early-life may be responsible for adverse effects in later life. This study aimed to assess the metabolic modifications induced in pregnant rats and their offspring by a pesticide mixture representative of human exposure.
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