Ferro Stefania, Buemi Maria Rosa, De Luca Laura, Agharbaoui Fatima E, Pannecouque Christophe, Monforte Anna-Maria
Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali (CHIBIOFARAM), Università degli Studi di Messina, Viale Annunziata, 98168 Messina, Italy.
KU Leuven, Department of Microbiology and Immunology, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
Bioorg Med Chem. 2017 Jul 15;25(14):3861-3870. doi: 10.1016/j.bmc.2017.05.040. Epub 2017 May 19.
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) represent an integral part of the currently available combination antiretroviral therapy (cART) contributing to reduce the AIDS-mortality and turned the disease from lethal to chronic. In this context we recently reported a series of 6-chloro-1-(3-methylphenylsulfonyl)-1,3-dihydro-2H-benzimidazol-2-ones as potent non-nucleoside HIV-1 reverse transcriptase inhibitors. In this paper, we describe the design and the synthesis of two novel series of benzimidazolone analogues in which the linker moiety between the phenyl ring and the sulfonyl group was modified and new small lipophilic groups on the benzyl sulfonyl pendant were introduced. All the new obtained compounds were evaluated as RT inhibitors and were also tested against RTs containing single amino acid mutations. Finally, molecular docking studies were performed in order to rationalize the observed activity of the most promising compound.
非核苷类逆转录酶抑制剂（NNRTIs）是目前可用的联合抗逆转录病毒疗法（cART）的一个组成部分，有助于降低艾滋病死亡率，并使这种疾病从致命性疾病转变为慢性疾病。在此背景下，我们最近报道了一系列6-氯-1-（3-甲基苯基磺酰基）-1,3-二氢-2H-苯并咪唑-2-酮作为有效的非核苷类HIV-1逆转录酶抑制剂。在本文中，我们描述了两个新型苯并咪唑酮类似物系列的设计与合成，其中苯环与磺酰基之间的连接部分被修饰，并且在苄基磺酰侧链上引入了新的小亲脂性基团。所有新得到的化合物都作为逆转录酶（RT）抑制剂进行了评估，并且还针对含有单个氨基酸突变的逆转录酶进行了测试。最后，进行了分子对接研究，以便对最有前景的化合物所观察到的活性进行合理分析。
