One-pot three steps cascade synthesis of novel isoandrographolide analogues and their cytotoxic activity

• DOI: 10.1016/j.ejmech.2017.07.035
• Publication Date: 2017-07-21T08:32:07Z
• Authors: Teerapich Kasemsuk; Pawinee Piyachatu...; Rada Bunthawong; Uthaiwan Sirion; Kanoknetr Suksen; Apichart Suksamrarn; Rungnapha Saeeng
• Keywords: 0301 basic medicine; Structure-Activity Relationship; 03 medical and health sciences; Dose-Response Relationship, Drug; Molecular Structure; Cell Line, Tumor; Humans; Andrographis; Antineoplastic Agents; Diterpenes; Drug Screening Assays, Antitumor; Cell Proliferation

An efficient one-pot synthesis of novel andrographolide analogues is reported from a naturally occurring and abundant andrographolide isolated from aerial parts of Andrographis paniculata. Reactions in the one-pot proceed through a cascade epoxide ring opening by aniline derivatives/intramolecular ring closing and oxa-conjugate addition-elimination reactions. This methodology produces a new series of 17-amino-8-epi-isoandrographolide analogues in fair to excellent yields with high stereoselectivity using an economic and environmental procedure without base or catalyst at room temperature. Twenty-five analogues were obtained and cytotoxicity of all new analogues were evaluated against six cancer cell lines to search for a new lead compound based on andrographolide structure.