Publications by authors named "Elisabeth Rivara-Minten"

5 Publications

  • Page 1 of 1

Production of Highly Active Antiparasitic Compounds from the Controlled Halogenation of the Crude Plant Extract.

J Nat Prod 2020 09 9;83(9):2631-2640. Epub 2020 Sep 9.

School of Pharmaceutical Sciences and Institute of Pharmaceutical Sciences of Western Switzerland (ISPSW), University of Geneva, CMU, Rue Michel Servet 1, 1211 Geneva 4, Switzerland.

Direct halogenation of phenolic compounds present in the CHCl extract of the roots of was investigated to enhance chemodiversity. The approach is based on eco-friendly reactions using NaBr, NaI, and NaCl in aqueous media to generate multiple "unnatural" halogenated natural products from crude extracts. The halogenation reactions, monitored by UHPLC-PDA-ELSD-MS, were optimized to generate mono-, di-, or trihalogenated derivatives. To isolate these compounds, the reactions were scaled up and the halogenated analogues were isolated by semipreparative HPLC-UV and fully characterized by NMR and HR-MS data. All of the original 16 halogenated derivatives were evaluated for their antiparasitic activities against the parasites and . Compounds presenting selective antiparasitic activities against one or both parasites with IC values comparable to the reference were identified.
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http://dx.doi.org/10.1021/acs.jnatprod.0c00433DOI Listing
September 2020

Generation of Stilbene Antimicrobials against Multiresistant Strains of through Biotransformation by the Enzymatic Secretome of .

J Nat Prod 2020 08 24;83(8):2347-2356. Epub 2020 Jul 24.

School of Pharmaceutical Sciences, University of Geneva, CMU, Rue Michel Servet 1, 1211 Geneva 4, Switzerland.

The biotransformation of a mixture of resveratrol and pterostilbene was performed by the protein secretome of Several reaction conditions were tested to overcome solubility issues and to improve enzymatic activity. Using MeOH as cosolvent, a series of unusual methoxylated compounds was generated. The reaction was scaled-up, and the resulting mixture purified by semipreparative HPLC-PDA-ELSD-MS. Using this approach, 15 analogues were isolated in one step. Upon full characterization by NMR and HRMS analyses, eight of the compounds were new. The antibacterial activities of the isolated compounds were evaluated in vitro against the opportunistic pathogens and . The selectivity index was calculated based on cytotoxic assays performed against human liver carcinoma cells (HepG2) and the human breast epithelial cell line (MCF10A). Some compounds revealed remarkable antibacterial activity against multidrug-resistant strains of with moderate human cell line cytotoxicity.
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http://dx.doi.org/10.1021/acs.jnatprod.0c00071DOI Listing
August 2020

New prostaglandin analog formulation for glaucoma treatment containing cyclodextrins for improved stability, solubility and ocular tolerance.

Eur J Pharm Biopharm 2015 Sep 8;95(Pt B):203-14. Epub 2015 May 8.

School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 30, Quai Ernest Ansermet, 1211 Geneva 4, Switzerland. Electronic address:

Latanoprost is a practically insoluble prostaglandin F2α analog considered a first-line agent for glaucoma treatment. From a pharmaceutical point of view, latanoprost is challenging to be formulated as an eye drop due to its poor water solubility and the presence of an ester bond that needs to be cleaved in vivo but maintained unchanged during storage. Cyclodextrins (CDs) are known to form complexes with hydrophobic drugs, influencing their stability, availability, solubility, and tolerance in a non-predictable manner. A variety of CDs including native α, β, and γCDs as well as substituted hydroxypropylβCD, hydroxypropylγCD, dimethylβCD, sulphatedβCD, and propylaminoβCD were screened and the most appropriate CD for the formulation of latanoprost for an ocular topical application was selected. Among the tested CDs, propylaminoβCD had the best trade-off between latanoprost stability and availability, which was confirmed by its complex constant value of 3129M(-1). Phase-solubility and NMR investigations demonstrated that the propylaminoβCD effectively formed a complex involving the ester group of latanoprost providing protection to its ester bond, while ensuring proper latanoprost solubilization. Furthermore, in vivo experiments demonstrated that the latanoprost-propylaminoβCD formulation led to lower ocular irritation than the commercial latanoprost formulation used as a reference. The latanoprost-propylaminoβCD formulation was demonstrated to successfully address the main stability, solubility, and tolerance limitations of topical ocular latanoprost therapy for glaucoma.
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http://dx.doi.org/10.1016/j.ejpb.2015.04.032DOI Listing
September 2015

Cancer chemopreventive diterpenes from Salvia corrugata.

Phytochemistry 2013 Dec 10;96:257-64. Epub 2013 Oct 10.

Department of Pharmacy, University of Genoa, via Brigata Salerno 13, 16147 Genoa, Italy.

NMR and NP-HPLC-UV profiling of the exudate of Salvia corrugata revealed that its secondary metabolite composition was largely dominated by α-hydroxy-β-isopropyl-benzoquinone diterpenoids. Among them, four diterpenes not described previously were isolated and identified as fruticulin C (3), 7α-methoxy-19-acetoxy-royleanone (4), 7α,19-diacetoxy-royleanone (5), and 7-dehydroxy-conacytone (7). In addition, the known diterpenes fruticulin A (1), demethyl-fruticulin A (2) and 7α-O-methyl-conacytone (6) were also obtained. The isolated compounds were evaluated for their cancer chemopreventive activity by measuring quinone reductase induction activity and histone deacetylase inhibition. Three compounds (1, 2 and 5) showed promising activity.
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http://dx.doi.org/10.1016/j.phytochem.2013.09.011DOI Listing
December 2013

Synthesis and in vitro cytotoxic and antiviral activities of 1-(2,5,6-trideoxy-6-halogenohept-5-enofuranurononitrile)thymine and derivatives.

Nucleosides Nucleotides Nucleic Acids 2002 ;21(3):191-206

Department of Organic Pharmaceutical Chemistry, University of Geneva, Sciences II, Switzerland.

All 1-(2,5,6-trideoxy-6-halogenohept-5-enofuranurononitrile)thymine and their 3'-O-TBDMS derivatives have been prepared and their configuration established. Some of these compounds are endowed with a cytotoxic or cytostatic activity in cell culture. The single most important factor affecting the cytotoxicity of these compounds is the presence on the molecule of a soft (electrofugal) halogen atom.
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http://dx.doi.org/10.1081/ncn-120003285DOI Listing
November 2002
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