Synthesis and cytotoxic evaluation of novel indenoisoquinoline-propan-2-ol hybrids

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• 作者：Tham Pham Thi^a ; ^b ; Lena Decuyper^c ; Tan Luc Quang^a ; Chinh Pham The^a ; ^b ; Tuyet Anh Dang Thi^a ; Ha Thanh Nguyen^a ; Thuy Giang Le Nhat^a ; Tra Nguyen Thanh^a ; Phuong Hoang Thi^a ; Matthias D&rsquo ; hooghe^c ; Tuyen Van Nguyen^a ;
• 关键词：Indenoisoquinolines ; β-Amino alcohols ; 2-Carboxybenzaldehyde ; Phthalide ; Cytotoxicity
• 刊名：Tetrahedron Letters
• 出版年：2016
• 出版时间：27 January 2016
• 年：2016
• 卷：57
• 期：4
• 页码：466-471
• 全文大小：2238 K

文摘

The synthesis of N-substituted indenoisoquinolines was performed by applying a two-step condensation between 2-carboxybenzaldehyde and phthalide, followed by treatment with various primary amines. N-allylindenoisoquinoline was subsequently selected as a substrate for hydroxybromination, providing 6-(3-bromo-2-hydroxy)indenoisoquinoline as a key intermediate for derivatization in the lactam side chain. In this way, a series of 6-(2-hydroxypropyl)indenoisoquinolines bearing various functional groups at the 3′-position were prepared, which can be considered as novel indenoisoquinoline-propan-2-ol hybrid molecules. Subsequent cytotoxic evaluation of 28 indenoisoquinolines against two human cancer cell lines (Hep-G2 and KB) demonstrated a moderate to high antiproliferative activity displayed by 11 indenoisoquinolines thus synthesized. In particular, the introduction of the 2-hydroxypropyl side chain was shown to be beneficial for the overall cytotoxic activity, pointing to the potential relevance of these novel indenoisoquinoline-propan-2-ol hybrids.