Botta Lorenzo, Maccari Giorgio, Calandro Pierpaolo, Tiberi Marika, Brai Annalaura, Zamperini Claudio, Canducci Filippo, Chiariello Mario, Martí-Centelles Rosa, Falomir Eva, Carda Miguel
Dipartimento di Farmacia, Università Federico II di Napoli, Via D. Montesano 49, 80131 Napoli, Italy.
Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via Aldo Moro 2, 53100 Siena, Italy.
Bioorg Med Chem Lett. 2017 Jun 1;27(11):2502-2505. doi: 10.1016/j.bmcl.2017.03.097. Epub 2017 Apr 1.
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.
与艾滋病相关的癌症疾病是在健康人群中发病率较低的恶性肿瘤，主要影响已经免疫功能低下的人群。艾滋病毒/艾滋病与这些癌症之间的联系尚未确定，但免疫系统减弱肯定是主要原因。我们设想有可能针对主要由艾滋病毒感染引起的机会性肿瘤（如伯基特淋巴瘤），筛选我们实验室合成的一个小型化合物库。通过细胞试验和基因表达分析，我们鉴定出了两种有前景的化合物。这些衍生物具有双重作用，既能抑制感染HIV-1 NL4.3的人TZM-bl细胞中的艾滋病毒复制，又能对人结肠HT-29细胞和乳腺腺癌MCF-7细胞显示细胞毒性活性。此外，临床前的体外吸收、分布、代谢和排泄研究突出了令人满意的药代动力学特征。
