Synthesis and cytotoxic evaluation of novel indenoisoquinoline-propan-2-ol hybrids. Issue 4 (27th January 2016)

• Record Type: Journal Article
• Authors: Thi, Tham Pham; Decuyper, Lena; Quang, Tan Luc; The, Chinh Pham; Dang Thi, Tuyet Anh; Nguyen, Ha Thanh; Le Nhat, Thuy Giang; Thanh, Tra Nguyen; Thi, Phuong Hoang; D'hooghe, Matthias; Van Nguyen, Tuyen
• Is Part Of: Tetrahedron letters. Volume 57:Issue 4(2016)
• Page Start: 466
• Page End: 471
• Publication Date: 2016-01-27
• Subjects: Indenoisoquinolines -- β-Amino alcohols -- 2-Carboxybenzaldehyde -- Phthalide -- Cytotoxicity; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2015.12.045
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Abstract: 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.