title: Synthesis of flavonoids based novel tetrahydropyran conjugates (Prins products) and their antiproliferative activity against human cancer cell lines.
abstract: Following our previously reported Prins cyclization strategy, a series of novel and highly functionalized flavonoid based THPs (Prins products) were designed, synthesized and evaluated for their antiproliferative activity. Novel products were afforded in excellent yields (72-96%) within 20-90 min at 62 °C using flavonoid aldehydes, homoallylic alcohols, p-TSA·H2O (catalyst and reagent) and MS 4 Å in CHCl3. Deprotection of tosyl group was achieved with TFA (catalyst and solvent) at 140 °C to obtain 4-hydroxytetrahydropyrans and further reaction of 4-hydroxytetrahydropyrans with cinnamoyl chloride afforded 4-cinnamate tetrahydropyrans under neat condition. Synthesized compounds evaluated against human cancer cell lines (Hep3β, MCF-7 and Hela), have shown moderate to good antiproliferative activity in vivo. Compounds 3q and 3zb exhibited similar cytotoxicity (IC50 6.6 ± 1.4, 6.9 ± 1.0 μM, respectively) to the reference drug doxorubicin (IC50 7.6 ± 0.9 μM) against the MCF-7 cancer cell line. Compound 3zb was found equally active as the standard drug (IC50 4.48 ± 2.1 μM) against the Hep3β cell line and compounds 3c and 3q showed moderate cytotoxicity (IC50 10.40 ± 1.1, 12.9 ± 1.7 μM, respectively) against the HeLa cell line.
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; D003500:Cyclization; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D011714:Pyrans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D011714:Pyrans
keywords: Antiproliferative activity; Flavonoids based tetrahydropyran conjugates; Homoallylic alcohols; Human cancer cell lines; Prins cyclization