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Synthesis, evaluation of cytotoxic properties of promising curcumin analogues and investigation of possible molecular mechanisms
Author(s) -
Jordan Brian C.,
Kumar Bhavna,
Thilagavathi Ramasamy,
Yadhav Arti,
Kumar Pawan,
Selvam Chelliah
Publication year - 2018
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13061
Subject(s) - curcumin , cytotoxicity , chemistry , pyrazole , lead compound , docking (animal) , in vitro , mtt assay , phosphorylation , potency , stereochemistry , pharmacology , biochemistry , medicine , nursing
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 CAL 27 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 pSTAT 3, pFAK , pERK 1/2 and pAKT was studied. Interestingly, compounds 2 and 5 significantly inhibited the pSTAT 3 (Tyr 705) phosphorylation. As far as other compounds, they showed potent cytotoxicity against CAL 27; however, these compounds did not show any activity on pSTAT 3 phosphorylation at IC 50 concentration level. Molecular docking studies revealed the possible binding mode of pyrazole compound 2 in the SH 2 domain of STAT3.