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Chem Biol Drug Des ; 90(3): 443-449, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28186369

ABSTRACT

The incidence of cancer can be decreased by chemoprevention using either natural or synthetic agents. Apart from synthetic compounds, numerous natural products have exhibited promising potential to inhibit carcinogenesis in vivo. In this study, α, ß-unsaturated carbonyl-based anticancer compounds were used as starting materials to synthesize new oxime analogs. The findings from the antiproliferative assay using seven different human cancer cell lines provided a clear picture of structure-activity relationship. The oxime analogs namely 7a and 8a showed strong antiproliferative activity against the cell lines. The mechanistic effects of compounds on EGFR-TK kinases and tubulin polymerization and BRAFV600E were investigated. In addition, the efficacy of compounds in reversing the efflux-mediated resistance developed by cancer cells was also studied. The compounds 5a and 6a displayed potent activity on various targets such as BRAFV600E and EGFR-TK kinases and also exhibited strong antiproliferative activity against different cell lines hence showing potential of multifunctional anticancer agents.


Subject(s)
Curcumin/analogs & derivatives , Curcumin/pharmacology , Oximes/chemistry , Oximes/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Curcumin/chemical synthesis , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Humans , Oximes/chemical synthesis , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins B-raf/metabolism , Structure-Activity Relationship , Tubulin/chemistry , Tubulin/metabolism , Tubulin Modulators/chemical synthesis , Tubulin Modulators/pharmacology
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