title: Design, synthesis and antiproliferative activity of functionalized flavone-triazole-tetrahydropyran conjugates against human cancer cell lines.
abstract: Under optimized reaction conditions, an efficient synthetic method has been developed to afford the functionalized flavone-triazole-tetrahydropyran conjugates via click reactions. The Cu-catalyzed 1,3-dipolar cycloaddition reaction gave the pure products, 5-iodo- and 5-H-1-(tetrahydropyran)-1,2,3-triazol-4-(3-methoxylflavone) derivatives in excellent yield (90-98%) within 1-3 h. Further, Pd-catalyzed Suzuki coupling of 5-iodo-1,2,3-triazoles with phenylboronic acids afforded 5-phenyl-1-(tetrahydropyran)-1,2,3-triazol-4-(3-methoxylflavone) derivatives in excellent yield (93-95%) in 4-5 h. Products (3a-l, 4a-j) were screened in vitro for their anti-proliferative activity against three human cancer cell lines (MDA-MB 231, KCL22 and Hela). Compounds 3c, 3g, 3i, 3j, 4c and 4h have shown better cytotoxicity (IC50 0.61-1.68 μM) than the reference drugs. Compounds 4e (IC50 0.70 μM), 3j (IC50 0.61 μM) and 4d (IC50 0.65 μM) exhibited anti-proliferative activity better than the reference drugs against the MDA-MB 231 cells, KCL22 cells and HeLa cells respectively.
authors.affiliation: Department of Chemistry, Indian Institute of Technology, Roorkee 247 667, Uttarakhand, India. Electronic address: nasemfcy@iitr.ac.in.
authors.forename: Naseem
authors.initials: N
authors.lastname: Ahmed
authors.affiliation: Department of Chemistry, Indian Institute of Technology, Roorkee 247 667, Uttarakhand, India.
authors.forename: Naveen Kumar
authors.initials: NK
authors.lastname: Konduru
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Sarfaraz
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Owais
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D047309:Flavones / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D011714:Pyrans / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D047309:Flavones; D011714:Pyrans; D014230:Triazoles; C043562:flavone
keywords: 3-(2-Propynyloxy) flavone; 4-Azido tetrahydropyran; 5-Iodo and 5-H-1-tetrahydropyran-1,2,3-triazol-4-(3-methoxylflavone) derivatives; Antiproliferative activity; Click chemistry