title: Synthesis and mechanistic studies of curcumin analog-based oximes as potential anticancer agents.
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, 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 BRAFV600Ewere 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 BRAFV600Eand EGFR-TK kinases and also exhibited strong antiproliferative activity against different cell lines hence showing potential of multifunctional anticancer agents.
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan, China.
authors.forename: Hua-Li
authors.initials: HL
authors.lastname: Qin
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Leng
authors.affiliation: Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut, Egypt.|Department of Pharmaceutical Chemistry, College of Pharmacy, Aljouf University, Sakaka, Saudi Arabia.
authors.forename: Bahaa G M
authors.identifier: http://orcid.org/0000-0002-6834-6548
authors.initials: BGM
authors.lastname: Youssif
authors.affiliation: College of Pharmacy, Northern Border University, Rafha, Saudia Arabia.
authors.forename: Muhammad Wahab
authors.initials: MW
authors.lastname: Amjad
authors.affiliation: College of Pharmacy, Northern Border University, Rafha, Saudia Arabia.
authors.forename: Maria Abdul Ghafoor
authors.initials: MAG
authors.lastname: Raja
authors.affiliation: Department of Chemistry, University of Sargodha, Sargodha, Pakistan.
authors.forename: Muhammad Ajaz
authors.initials: MA
authors.lastname: Hussain
authors.affiliation: Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam, Selangor, Malaysia.
authors.forename: Zahid
authors.initials: Z
authors.lastname: Hussain
authors.affiliation: Department of Mathematics, Capital University of Science and Technology (CUST), Islamabad, Pakistan.
authors.forename: Syeda Naveed
authors.initials: SN
authors.lastname: Kazmi
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan, China.|Department of Pharmaceutical Chemistry, College of Pharmacy, Aljouf University, Sakaka, Saudi Arabia.
authors.forename: Syed Nasir Abbas
authors.identifier: http://orcid.org/0000-0001-8125-7972
authors.initials: SNA
authors.lastname: Bukhari
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D010091:Oximes; D014404:Tubulin; D050257:Tubulin Modulators; D066246:ErbB Receptors; D048493:Proto-Oncogene Proteins B-raf; D003474:Curcumin
keywords: Natural compounds; epidermal growth factor receptor (EGFR); multidrug resistance (MDR); tubulin polymerization; α, β-unsaturated carbonyl