Design and synthesis of novel iminothiazinylbutadienols and divinylpyrimidinethiones as ARE inducers

Lin Chen; Sadagopan Magesh; Hong Wang; Chung S Yang; Ah-Ng Tony Kong; Longqin Hu

doi:10.1016/j.bmcl.2013.12.072

Design and synthesis of novel iminothiazinylbutadienols and divinylpyrimidinethiones as ARE inducers

Bioorg Med Chem Lett. 2014 Feb 1;24(3):940-3. doi: 10.1016/j.bmcl.2013.12.072. Epub 2013 Dec 24.

Authors

Lin Chen¹, Sadagopan Magesh¹, Hong Wang², Chung S Yang³, Ah-Ng Tony Kong⁴, Longqin Hu⁵

Affiliations

¹ Department of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA.
² Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA.
³ Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA; The Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA; Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
⁴ Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA; The Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA; Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
⁵ Department of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA; School of Pharmaceutical Sciences, Shanxi Medical University, Taiyuan 030001, PR China; The Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA; Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA. Electronic address: [email protected].

Abstract

Novel iminothiazinylbutadienols and divinylpyrimidinethiones were designed and synthesized as analogues of curcumin with its diketone moiety masked as a heterocyclic adduct with thiourea. The chemical stability of these novel heterocyclic compounds was improved as compared to curcumin. They exhibit longer half-lives and do not react with nucleophilic thiols under physiological conditions. In an ARE-luciferase reporter assay, some of these new curcumin analogues are more effective ARE activators than curcumin and isothiocyanates.

Keywords: ARE induction; Anti-inflammatory agents; Curcumin; Divinylpyrimidinethiones; Iminothiazinylbutadienols.

Publication types

Comparative Study
Research Support, N.I.H., Extramural

MeSH terms

Antioxidant Response Elements / drug effects*
Curcumin / chemistry
Curcumin / metabolism
Drug Design*
Isothiocyanates / chemistry
Isothiocyanates / pharmacology
Molecular Structure
Pyrimidines / chemical synthesis
Pyrimidines / chemistry
Pyrimidines / pharmacology
Structure-Activity Relationship
Sulfoxides
Thiadiazines / chemical synthesis
Thiadiazines / chemistry
Thiadiazines / pharmacology
Thiones / chemical synthesis
Thiones / chemistry*
Thiones / pharmacology
Thiourea / chemistry
Thiourea / metabolism

Substances

Isothiocyanates
Pyrimidines
Sulfoxides
Thiadiazines
Thiones
sulforaphane
Thiourea
Curcumin
dazomet

Abstract

Publication types

MeSH terms

Substances

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