Rubipodanin B, a New Cytotoxic Cyclopeptide from Rubia podantha

Using the TLC cyclopeptide protosite detection method, a new cyclohexapeptide named rubipodanin B (1), together with 11 known Rubiaceae-type cyclopeptides (RAs), RA-X-OMe (2), RA-IV (3), RA-XI (4), RA-XIII-OMe (5), rubiyunnanin C (6), RA-I (7), RA-III (8), RA-V (9), RA-VII (10), RA-XII (11) and rubipodanin A (12), were obtained from the roots and rhizomes of Rubia podantha Diels. The structures were determined using various spectroscopic methods. Among them, 2 was firstly identified as a natural product, and 3-6 were firstly isolated from this species. Cytotoxicity and NF-κB signaling pathway activity of 1, 2, 4, 6, 7 and 9 were evaluated. All these compounds showed cytotoxic activities against three human tumor cell lines, MDA-MB-231, SW620 and HepG2, with the IC₅₀ values between 0.015 and 10.27 μm, and only 7 and 9 possessed NF-κB inhibitory activities with the IC₅₀ values of 2.42 and 0.046 μm, respectively, which demonstrated that 2-alanine amino acid plays a key role to maintain the RAs bioactivity.