Rubipodanin A, the First Natural N-Desmonomethyl Rubiaceae-Type Cyclopeptide from Rubia podantha, Indicating an Important Role of the N9-Methyl Group in the Conformation and Bioactivity

Abstract

One new cyclic hexapeptide named rubipodanin A (1), which is the first identified natural N-desmonomethyl Rubiaceae-type cyclopeptide, together with six known Rubiaceae-type cyclopeptides (2–7) were obtained using the TLC cyclopeptide protosite detection method with ninhydrin from the roots and rhizomes of Rubia podantha. The cyclopeptide structures were elucidated by extensive spectroscopic analysis, including 1D-NMR, 2D-NMR, IR, UV and MS. The solution conformation and biological activities of 1 and RA-V (4) were evaluated, and the results demonstrated that the N 9-methyl group plays a vital role in the maintenance of the conformation and 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].…”

Design and Synthesis of Analogues of Marine Natural Product Galaxamide, an N-methylated Cyclic Pentapeptide, as Potential Anti-Tumor Agent in Vitro

“…Thus, the chemopreventive agents that can modulate apoptosis, are often useful in cancer therapy. Recently, the anti-tumor activity of cyclic peptides has attracted much attention [ 44 ]. Many natural and synthetic cyclopeptides have been proven to be clinically effective for treating cancer could inhibit tumors by triggering cancer cell apoptosis.…”

Toward the Synthesis and Pharmacological Screening of a Natural Cycloheptapeptide of Plant Origin

“…Natural products from the medicinal plants provide unlimited opportunities for new drug leads because of their unmatched availability of chemical diversity [2]. Among bioactive natural products, cyclopolypeptides are hot spots in chemical and pharmaceutical fields because of the wide spread bio-resources, complex molecular structures and wide spectrum of pharmacological activities [3][4][5][6][7][8][9][10]. A cyclic heptapeptide, gypsophin E was isolated from roots of Gypsophila oldhamiana (Caryophyllaceae) and its structure elucidated by extensive NMR and chemical degradation [11].…”

“…The cycloheptapeptide molecule was split into three dipeptide units Boc-Gly-L-Leu-OMe (1), Boc-L-Val-L-Pro-OMe (2) and Boc-L-Ile-Gly-OMe (3) and a single amino acid unit L-Pro-OMe•HCl (4). Dipeptide units 1-3 were prepared by the coupling of Boc-amino acids such as Boc-Gly, Boc-L-Val and Boc-L-Ile with corresponding amino acid methyl ester hydrochlorides such as L-Leu-OMe•HCl, L-Pro-OMe•HCl and Gly-OMe•HCl by following the modified Bodanzsky and Bodanzsky method [16].…”