2. Academic Validation
  3. One drug for two targets: Biological evaluation of antiretroviral agents endowed with antiproliferative activity

One drug for two targets: Biological evaluation of antiretroviral agents endowed with antiproliferative activity

  • Bioorg Med Chem Lett. 2017 Jun 1;27(11):2502-2505. doi: 10.1016/j.bmcl.2017.03.097.
Lorenzo Botta 1,  Giorgio Maccari 2,  Pierpaolo Calandro 2,  Marika Tiberi 2,  Annalaura Brai 2,  Claudio Zamperini 2,  Filippo Canducci 3,  Mario Chiariello 4,  Rosa Martí-Centelles 5,  Eva Falomir 5,  Miguel Carda 5
Affiliations

Affiliations

  • 1 Dipartimento di Farmacia, Università Federico II di Napoli, Via D. Montesano 49, 80131 Napoli, Italy. Electronic address: lorenzo.botta@unina.it.
  • 2 Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via Aldo Moro 2, 53100 Siena, Italy.
  • 3 Department of Clinical and Experimental Medicine, Università degli Studi dell'Insubria, Varese, Italy.
  • 4 Istituto Toscano Tumori (ITT), Core Research Laboratory (CRL), AOU Senese, Siena, Italy.
  • 5 Departamento de Química Inorgánica y Orgánica, Universidad Jaume I, E-12071 Castellón, Spain.
PMID: 28408224 DOI: 10.1016/j.bmcl.2017.03.097
Abstract

AIDS-related Cancer diseases are malignancies with low incidence on healthy people that affect mostly subjects already immunocompromised. The connection between HIV/AIDS and these cancers has not been established yet, but a weakened immune system is certainly the main cause. We envisaged the possibility to screen a small library of compounds synthesized in our laboratory against opportunistic tumors mainly due to HIV Infection like Burkitt's Lymphoma. From cellular assays and gene expression analysis we identified two promising compounds. These derivatives have the dual action required inhibiting HIV replication in human TZM-bl cells infected with HIV-1 NL4.3 and showing cytotoxic activity on human colon HT-29 and breast adenocarcinoma MCF-7 cells. In addition, preclinical in vitro adsorption, distribution, metabolism, and excretion studies highlighted a satisfactory pharmacokinetic profile.

Keywords

Burkitt’s Lymphoma; Cancer; HIV; c-Myc; hTERT.

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