Synthesis and biological evaluation of novel C6-amino substituted 4-azasteroidal purine nucleoside analogues

• Published in: Bioorganic & medicinal chemistry letters Vol. 24; no. 3; pp. 973 - 975
• Main Authors: Huang, Li-Hua, Xu, Hong-De, Yao, Zhen-Yu, Wang, Yan-Guang, Liu, Hong-Min
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.02.2014; Elsevier
• Subjects: 4-Azasteroid; Amines; Anticancer activity; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Azasteroids - chemical synthesis; Azasteroids - chemistry; Azasteroids - pharmacology; Cell Line, Tumor; Cell Survival - drug effects; Chemistry; Chemistry, Medicinal; Chemistry, Organic; HeLa Cells; Humans; Inhibitory Concentration 50; Life Sciences & Biomedicine; MCF-7 Cells; Molecular Structure; Nucleoside analogues; Pharmacology & Pharmacy; Physical Sciences; Purine; Purine Nucleosides - chemical synthesis; Purine Nucleosides - chemistry; Purine Nucleosides - pharmacology; Science & Technology; Structure-Activity Relationship; Purine; Amines; 4-Azasteroid; Nucleoside analogues; Anticancer activity; DESIGN; BASES; NUCLEOSTEROIDS; KINASE INHIBITORS; ANTIVIRAL ACTIVITIES; STEROID-NUCLEOSIDES; CANCER; ANTICANCER; AGENTS; DERIVATIVES
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2013.12.056

Novel C6-amino substituted purine nucleoside analogues (2–12) bearing a modified pyranose-like D ring of the 4-azasteroid moiety were efficiently synthesized through nucleophilic substitution at C6 position of the steroidal nucleoside precursors (1a, b) with versatile amines. All the synthesized new compounds were evaluated for their anticancer activity in vitro against Hela, PC-3 and MCF-7 cell lines. Among them, compounds 4b, 7b and 9b exhibited significant cytotoxicity with the IC50 values of 2.99μM (PC-3), 2.84μM, (PC-3) and 2.69μM (Hela), respectively.