title: Novel autophagy inducers lentztrehaloses A, B and C.
abstract: Trehalose has widespread use as a sweetener, humectant and stabilizer, and is now attracting attention as a promising candidate for the treatment of neurodegenerative diseases as it is an autophagy inducer and chemical chaperone. However, the bioavailability of trehalose is low because it is digested by the hydrolyzing enzyme trehalase, expressed in the intestine and kidney. Enzyme-stable analogs of trehalose would potentially solve this problem. We have previously reported an enzyme-stable analog of trehalose, lentztrehalose, and herein report two new analogs. The original lentztrehalose has been renamed lentztrehalose A and the analogs named lentztrehaloses B and C. Lentztrehalose B is a di-dehydroxylated analog and lentztrehalose C is a cyclized analog of lentztrehalose A. All the lentztrehaloses are only minimally hydrolyzed by mammalian trehalase. The production of the lentztrehaloses is high in rather dry conditions and low in wet conditions. Lentztrehalose B shows a moderate antioxidative activity. These facts suggest that the lentztrehaloses are produced as humectants or protectants for the producer microorganism under severe environmental conditions. All the lentztrehaloses induce autophagy in human cancer cells at a comparable level to trehalose. Considering the enzyme-stability, these lentztrehaloses can be regarded as promising new drug candidates for the treatment of neurodegenerative diseases and other autophagy-related diseases, such as diabetes, arteriosclerosis, cancer and heart disease.
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.
authors.forename: Shun-ichi
authors.initials: S
authors.lastname: Wada
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kubota
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Sawa
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.
authors.forename: Maya
authors.initials: M
authors.lastname: Umekita
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Hatano
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.
authors.forename: Shun-ichi
authors.initials: S
authors.lastname: Ohba
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.
authors.forename: Chigusa
authors.initials: C
authors.lastname: Hayashi
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Igarashi
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Nomoto
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004355:Drug Stability; D006801:Humans; D006868:Hydrolysis; D015394:Molecular Structure; D014198:Trehalase / Q000378:metabolism; D014199:Trehalose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism
chemical_list: C000588806:4-O-(2,3-dihydroxy-3-methylbutyl)trehalose; D014199:Trehalose; D014198:Trehalase