Synthesis and biological profiling of tellimagrandin I and analogues reveals that the medium ring can significantly modulate biological activity

• Published in: Organic & biomolecular chemistry Vol. 10; no. 13; pp. 2590 - 2593
• Main Authors: Zheng, Shaojun, Laraia, Luca, Connor, Cornelius J. O', Sorrell, David, Tan, Yaw Sing, Xu, Zhaochao, Venkitaraman, Ashok R., Wu, Wenjun, Spring, David R.
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 07.04.2012
• Subjects: Apoptosis - drug effects; Chemistry; Chemistry, Organic; Gallic Acid - analogs & derivatives; Gallic Acid - chemical synthesis; Gallic Acid - chemistry; Gallic Acid - pharmacology; Glucosides - chemical synthesis; Glucosides - chemistry; Glucosides - pharmacology; HeLa Cells; Humans; Molecular Structure; Phenotype; Physical Sciences; Science & Technology; Structure-Activity Relationship; TOTAL CHEMICAL-SYNTHESIS; EFFICIENT TOTAL-SYNTHESIS; DIMERIC ELLAGITANNIN; NATURAL-PRODUCTS; TANNINS; 1ST TOTAL-SYNTHESIS; ELLAGITANNIN CHEMISTRY; MECHANISMS; CANCER; RELEVANT
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c2ob25065a

A novel synthesis of the ellagitannin natural product tellimagrandin I and a series of medium ring analogues is described. These compounds were all subsequently screened for redox activity, ability to precipitate protein and cellular phenotype in HeLa cells. From this we have shown that all properties can be modulated independently by varying ring size and by moving the ester out of conjugation with the biaryl ring system. Increasing ring size increased redox activity and cytotoxicity, leading to the identification of a compound (10) which was significantly more cytotoxic. In addition compounds identified with a redox active scaffold and low cytotoxicity may be employed as a new class of redox probes.