Rubipodanin B, a New Cytotoxic Cyclopeptide from Rubia podantha

Abstract

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.

Natural Naphthohydroquinone Dimer Rubioncolin C Exerts Anti-Tumor Activity by Inducing Apoptotic and Autophagic Cell Death and Inhibiting the NF-κB and Akt/mTOR/P70S6K Pathway in Human Cancer Cells

“…The roots and rhizomes of several Rubia plants have been widely used for the treatment of cancer, menoxenia, rheumatism, and tuberculosis, especially R. cordifolia, which was recorded as a traditional Chinese medicine in all editions of Chinese Pharmacopeia. In previous studies, we have obtained nearly 200 compounds from nine Rubia plants, including R. cordifolia, R. yunnanesis, R. podantha, R. schumanniana, R. alata, R. wallichiana, R. oncotricha, R. sylvatica, and R. ovatifolia, and investigated their bioactivities and mechanisms of action, including Rubiaceae-type cyclopeptides [6][7][8][9][10], quinones [5,15,16,[27][28][29], triterpenes [27,30,31]. For their unique structures and preferable bioactivities, naphthohydroquinone dimers have attracted our attention, especially rubioncolin C (RC) which exhibits the best cytotoxicity among them.…”

“…Among them, naphthohydroquinone dimers have drawn more attentions for their distinctive chemical structures and intriguing bioactivities [5]. The roots and rhizomes of Rubia plants, especially R. cordifolia, R. yunnanensis and R. podantha, have been widely used as traditional Chinese medicines for treating cancer, menoxenia, rheumatism and tuberculosis [6][7][8][9][10]. To date, 17 naphthohydroquinone dimers have been isolated from Rubia plants [5,[11][12][13][14][15][16][17] (Figure S1), and some of 2 of 17 them have been synthesized totally [18][19][20].…”

Natural Cyclopeptides as Anticancer Agents in the Last 20 Years

“…This compound showed IC 50 values of 1.47 μM, 0.69 μM and 3.37 μM in MDA-MB-231, SW620 (human colorectal adenocarcinoma) and HepG2 cells respectively. Nevertheless, the anticancer activity of rubipodanin B was not associated with any down-regulation of the NF-κB signaling pathway [ 144 ]. Another cyclopeptide compound from RA family is RA-XII ( 89 ), which derived from R. yunnanensis , showed inhibitory effects on tumor growth and metastasis IC 50 value of 606 nM and 96 nM on human breast cancer 4T1 cells for 24 and 48 h, respectively [ 145 , 146 , 147 ].…”

Diversity of cultivable endophytic fungi in two Rubia plants and their potential for production of anti‐tumour Rubiaceae‐type cyclopeptides

“…For example, Rubia cordifolia was used to treat cancer for a long time and its roots and rhizomes were recorded as a traditional Chinese medicine named 'Qian Cao' (Rubiae Radix et Rhizoma) in Chinese Pharmacopoeia (2020 version) to treat tuberculosis, Letters in Applied Microbiology 73, 759--769 © 2021 The Society for Applied Microbiology rheumatism, menoxenia and contusion. Rubia podantha is native to China, and its roots and rhizomes had been used as the substituent of R. cordifolia (Hu et al 2019). In addition, there were numerous prescriptions involved in Rubia species in Indian folk medicine, which were used for healing wounds, skin infections and inflammation (Meena et al 2010).…”

“…RAs are composed of one a-D-alanine, one a-Lalanine, three N-methyl-a-L-tyrosines and one other proteinogenic a-L-amino acid (Tan and Zhou 2006;Zhao et al 2011a;Xu et al 2013). To date, 58 natural RAs have been obtained, and their various antitumor mechanisms were reported (Hu et al 2019). We have isolated 32 RAs including 13 new ones and synthesized several RA analogues (Fan et al 2010a(Fan et al , 2010bKuang et al 2012;Huang et al 2014;Liu et al 2014;Chen et al 2015;Wang et al 2015).…”