title: Microwave-assisted synthesis of 3,5-disubstituted isoxazoles and evaluation of their anti-ageing activity.
abstract: One-pot uncatalysed microwave-assisted 1,3-dipolar cycloaddition reactions between in situ generated nitrile oxides and alkynes bearing protected antioxidant substituents, were regioselectively afforded 3,5-disubstituted isoxazoles. The yields were moderate, based on the starting aldehydes, while the reaction times were in general shorter than those reported in the literature. The cytoprotective and anti-ageing effect of the final deprotected compounds was evaluated in vitro, on cellular survival following oxidative challenge and in vivo, on organismal longevity using the nematode Caenorhabditis elegans. The activity of the isoxazole analogues depends on the nature and the number of the antioxidant substituents. Analogue 17 bearing a phenolic group and a 6-OH-chroman group is a promising anti-ageing agent, since it increased survival of human primary fibroblasts following treatment with H2O2 and extended C. elegans lifespan.
authors.affiliation: National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, 48 Vas. Constantinou Ave, Athens 11635, Greece. Electronic address: mkoufa@eie.gr.
authors.forename: Maria
authors.initials: M
authors.lastname: Koufaki
authors.affiliation: National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, 48 Vas. Constantinou Ave, Athens 11635, Greece.
authors.forename: Theano
authors.initials: T
authors.lastname: Fotopoulou
authors.affiliation: National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, 48 Vas. Constantinou Ave, Athens 11635, Greece.
authors.forename: Marianna
authors.initials: M
authors.lastname: Kapetanou
authors.affiliation: National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, 48 Vas. Constantinou Ave, Athens 11635, Greece.
authors.forename: Georgios A
authors.initials: GA
authors.lastname: Heropoulos
authors.affiliation: National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, 48 Vas. Constantinou Ave, Athens 11635, Greece.
authors.forename: Efstathios S
authors.initials: ES
authors.lastname: Gonos
authors.affiliation: National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, 48 Vas. Constantinou Ave, Athens 11635, Greece.
authors.forename: Niki
authors.initials: N
authors.lastname: Chondrogianni
mesh_terms: D000375:Aging / Q000187:drug effects*; D000480:Alkynes / Q000737:chemistry; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D060326:Chemistry Techniques, Synthetic; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008136:Longevity / Q000187:drug effects; D008872:Microwaves; D018384:Oxidative Stress / Q000187:drug effects; D010087:Oxides / Q000737:chemistry; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D000480:Alkynes; D007555:Isoxazoles; D010087:Oxides
keywords: Anti-ageing; Antioxidant; Caenorhabditis elegans; Isoxazole; Microwave