Synthesis and mechanistic studies of curcumin analog‐based oximes as potential anticancer agents

• Published in: Chemical biology & drug design 2017-09, Vol.90 (3), p.443-449
• Main Authors: Qin, Hua‐Li, Leng, Jing, Youssif, Bahaa G. M., Amjad, Muhammad Wahab, Raja, Maria Abdul Ghafoor, Hussain, Muhammad Ajaz, Hussain, Zahid, Kazmi, Syeda Naveed, Bukhari, Syed Nasir Abbas
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Curcumin - analogs & derivatives; Curcumin - chemical synthesis; Curcumin - pharmacology; epidermal growth factor receptor (EGFR); Humans; multidrug resistance (MDR); Natural compounds; Oximes - chemical synthesis; Oximes - chemistry; Oximes - pharmacology; Proto-Oncogene Proteins B-raf - antagonists & inhibitors; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins B-raf - metabolism; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - metabolism; Structure-Activity Relationship; Tubulin - chemistry; Tubulin - metabolism; Tubulin Modulators - chemical synthesis; Tubulin Modulators - pharmacology; tubulin polymerization; α, β‐unsaturated carbonyl
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/cbdd.12964

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, β‐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. Newly synthesized oxime analogs showed strong antiproliferative activity against the cancer cell lines. The mechanistic effects of compounds on EGFR‐TK kinases and tubulin polymerization and BRAFV600E were also investigated.