Publications by authors named "Claudio Zippilli"

4 Publications

  • Page 1 of 1

Stereoselective Access to Antimelanoma Agents by Hybridization and Dimerization of Dihydroartemisinin and Artesunic acid.

ChemMedChem 2021 Apr 1. Epub 2021 Apr 1.

Department of Biological and Ecological Sciences, Univeristy of Viterbo, Via S.C. De Lellis s.n.c., 01100, Viterbo, Italy.

A library of five hybrids and six dimers of dihydroartemisinin and artesunic acid has been synthetized in a stereo-controlled manner and evaluated for the anticancer activity against metastatic melanoma cell line (RPMI7951). Among novel derivatives, three artesunic acid dimers showed antimelanoma activity and cancer selectivity, being not toxic on normal human fibroblast (C3PV) cell line. Among the three dimers, the one bearing 4-hydroxybenzyl alcohol as a spacer showed no cytotoxic effect (CC >300 μM) and high antimelanoma activity (IC =0.05 μM), which was two orders of magnitude higher than that of parent artesunic acid, and of the same order of commercial drug paclitaxel. In addition, this dimer showed cancer-type selectivity towards melanoma compared to prostate (PC3) and breast (MDA-MB-231) tumors. The occurrence of a radical mechanism was hypothesized by DFO and EPR analyses. Qualitative structure activity relationships highlighted the role of artesunic acid scaffold in the control of toxicity and antimelanoma activity.
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http://dx.doi.org/10.1002/cmdc.202100196DOI Listing
April 2021

Laccase-Catalyzed 1,4-Dioxane-Mediated Synthesis of Belladine -Oxides with Anti-Influenza A Virus Activity.

Int J Mol Sci 2021 Jan 29;22(3). Epub 2021 Jan 29.

Department of Ecology and Biology, University of Tuscia, 01100 Viterbo, Italy.

Belladine -oxides active against influenza A virus have been synthetized by a novel laccase-catalyzed 1,4-dioxane-mediated oxidation of aromatic and side-chain modified belladine derivatives. Electron paramagnetic resonance (EPR) analysis confirmed the role of 1,4-dioxane as a co-oxidant. The reaction was chemo-selective, showing a high functional-group compatibility. The novel belladine -oxides were active against influenza A virus, involving the early stage of the virus replication life cycle.
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http://dx.doi.org/10.3390/ijms22031337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866262PMC
January 2021

Artemisinin Derivatives with Antimelanoma Activity Show Inhibitory Effect against Human DNA Topoisomerase 1.

ACS Med Chem Lett 2020 May 10;11(5):1035-1040. Epub 2020 Apr 10.

Dipartimento di Biologia, Università di Padova Distaccato presso il "Centro Linceo Beniamino Segre" Accademia Nazionale dei Lincei, Palazzo Corsini, Via della Lungara 10, 00165 Rome, Italy.

Artesunic acid and artemisinin are natural substances with promiscuous anticancer activity against different types of cancer cell lines. The mechanism of action of these compounds is associated with the formation of reactive radical species by cleavage of the sesquiterpene pharmacophore endoperoxide bridge. Here we suggested topoisomerase 1 as a possible molecular target for the improvement of the anticancer activity of these compounds. In this context, we report that novel hybrid and dimer derivatives of artesunic acid and artemisinin, bearing camptothecin and SN38 as side-chain biological effectors, can inhibit growth of yeast cells overexpressing human topoisomerase 1 and its enzymatic activity . These derivatives showed also anticancer activity in melanoma cell lines higher than camptothecin and paclitaxel. molecular docking calculations highlighted a common binding mode for the novel derivatives, with the sesquiterpene lactone scaffold being located near the traditional recognition site for camptothecin, while the bioactive side-chain effector laid in the camptothecin cleft.
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http://dx.doi.org/10.1021/acsmedchemlett.0c00131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236541PMC
May 2020

Synthesis and Evaluation of Artemisinin-Based Hybrid and Dimer Derivatives as Antimelanoma Agents.

ACS Omega 2020 Jan 27;5(1):243-251. Epub 2019 Dec 27.

Department of Ecological and Biological Sciences, University of Tuscia, via S. C. De Lellis 44, 01100, Viterbo, Italy.

A library of hybrid and dimer compounds based on the natural scaffold of artemisinin was synthesized. These derivatives were obtained by coupling of artemisinin derivatives, artesunate, and dihydroartemisinin with a panel of phytochemical compounds. The novel artemisinin-based hybrids and dimers were evaluated for their anticancer activity on a cervical cancer cell line (HeLa) and on three complementary metastatic melanoma cancer cell lines (SK-MEL3, SK-MEL24, and RPMI-7951). Two hybrid compounds obtained by coupling of artesunate with eugenol and tyrosol, and one of the dimer compounds containing curcumin, emerged as the most active and cancer-selective derivatives.
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http://dx.doi.org/10.1021/acsomega.9b02600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964273PMC
January 2020