Natural Science Laboratory, Division of Pharmaceutical & Medicinal Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India.
Department of Chemistry & Biochemistry, University of Porto, Portugal.
Future Med Chem. 2022 Jan;14(1):17-34. doi: 10.4155/fmc-2021-0049. Epub 2021 Nov 25.
Our previous results suggest that phenyl/naphthylacetyl pentanoic acid derivatives may exhibit dual MMP-2 and HDAC8 inhibitory activities and show effective cytotoxic properties. Here, 13 new compounds () were synthesized and characterized. Along with these new compounds, 16 previously reported phenyl/napthylacetyl pentanoic acid derivatives () were biologically evaluated. Compounds and showed good cytotoxicity against leukemia cell line Jurkat E6.1. The mechanisms of cytotoxicity of these compounds were confirmed by DNA deformation assay and reactive oxygen species assay. MMP-2 and HDAC8 expression assays suggested the dual inhibiting property of these two compounds. These findings were supported by results of molecular docking studies. pharmacokinetic properties showed compounds and have high gastrointestinal absorption. This study highlights the action of phenyl/naphthylacetyl pentanoic acid derivatives as anticancer agents.
我们之前的研究结果表明，苯/萘乙酰基戊酸衍生物可能具有双重 MMP-2 和 HDAC8 抑制活性，并表现出有效的细胞毒性。在此，合成并表征了 13 个新化合物（）。除了这些新化合物，还对 16 个先前报道的苯/萘乙酰基戊酸衍生物（）进行了生物评价。化合物和对白血病细胞系 Jurkat E6.1 表现出良好的细胞毒性。通过 DNA 变形试验和活性氧测定证实了这些化合物的细胞毒性机制。MMP-2 和 HDAC8 表达试验表明这两种化合物具有双重抑制作用。分子对接研究结果支持了这些发现。药代动力学特性表明化合物和具有较高的胃肠道吸收。本研究强调了苯/萘乙酰基戊酸衍生物作为抗癌剂的作用。
