Synthesis, evaluation of cytotoxic properties of promising curcumin analogues and investigation of possible molecular mechanisms

被引：26
作者：
Jordan, Brian C. [1 ]
Kumar, Bhavna [2 ]
Thilagavathi, Ramasamy [3 ]
Yadhav, Arti [2 ]
Kumar, Pawan [2 ]
Selvam, Chelliah [1 ]
机构：
[1] Texas Southern Univ, Dept Pharmaceut Sci, Coll Pharm & Hlth Sci, Houston, TX 77004 USA
[2] Ohio State Univ, Dept Otolaryngol Head & Neck Surg, Wexner Med Ctr, Columbus, OH 43210 USA
[3] Karpagam Univ, Dept Biotechnol, Fac Engn, Coimbatore, Tamil Nadu, India
来源：
CHEMICAL BIOLOGY & DRUG DESIGN | 2018年 / 91卷 / 01期
关键词：
click chemistry curcumin analogue; curcumin; head and neck squamous cell carcinoma; pyrazole analogue; CONFORMER GENERATION; CANCER PREVENTION; HEAD; DERIVATIVES; DOCKING; DESIGN; CELLS;
D O I：
10.1111/cbdd.13061
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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 IC50 concentration level. Molecular docking studies revealed the possible binding mode of pyrazole compound 2 in the SH2 domain of STAT3.
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收藏
页码：332 / 337
页数：6
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