Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, USA.
Department of Otolaryngology-Head and Neck Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Chem Biol Drug Des. 2018 Jan;91(1):332-337. doi: 10.1111/cbdd.13061. Epub 2017 Jul 18.
Curcumin is a popular, plant-derived compound that has been extensively investigated for diverse range of biological activities. Anticancer activity against various types of cancers and high-safety profile associated with curcumin makes it very attractive. In this study, we report the synthesis and evaluation of pyrazole and click chemistry curcumin analogues for Head and Neck cancer. MTT assay against head and neck cancer cell lines CAL27 and UM-SCC-74A revealed the micromolar potency of the synthesized compounds. To determine the possible molecular mechanisms, effect of these analogues in the expression of pSTAT3, pFAK, pERK1/2 and pAKT was studied. Interestingly, compounds 2 and 5 significantly inhibited the pSTAT3 (Tyr 705) phosphorylation. As far as other compounds, they showed potent cytotoxicity against CAL27; however, these compounds did not show any activity on pSTAT3 phosphorylation at IC concentration level. Molecular docking studies revealed the possible binding mode of pyrazole compound 2 in the SH2 domain of STAT3.
姜黄素是一种广受欢迎的植物衍生化合物，已被广泛研究用于多种生物活性。姜黄素具有针对各种类型癌症的抗癌活性和高安全性，这使其极具吸引力。在这项研究中，我们报告了用于头颈部癌症的吡唑和点击化学姜黄素类似物的合成和评估。MTT 分析对头颈部癌细胞系 CAL27 和 UM-SCC-74A 的测定揭示了合成化合物的微摩尔效力。为了确定可能的分子机制，研究了这些类似物对 pSTAT3、pFAK、pERK1/2 和 pAKT 表达的影响。有趣的是，化合物 2 和 5 显著抑制了 pSTAT3（Tyr705）磷酸化。就其他化合物而言，它们对 CAL27 表现出很强的细胞毒性；然而，这些化合物在 IC 浓度水平下对 pSTAT3 磷酸化没有显示出任何活性。分子对接研究揭示了吡唑化合物 2 在 STAT3 的 SH2 结构域中的可能结合模式。
