Ascidiacyclamides containing oxazoline and thiazole motifs assume square conformations and show high cytotoxicity |
| |
| Authors: | Akiko Asano Takeshi Yamada Taizo Taniguchi Masahiro Sasaki Kenji Yoza Mitsunobu Doi |
| |
| Affiliation: | 1. Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan;2. Himeji Dokkyo University, Himeji, Japan;3. Molecular Imaging Group, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan;4. Bruker AXS, Yokohama, Kanagawa, Japan |
| |
| Abstract: | Four cyclic octapeptides were designed from ascidiacyclamide cyclo(–Ile–Oxz–D ‐Val– Thz–)2] (ASC, 1 ) to investigate the effects of oxazoline (Oxz) and thiazole (Thz) rings on the structures and cytotoxicities of the peptides. cyclo(–Ile–Thz–D ‐Val–Oxz–)2 ( 2 ) had the same number of Oxz and Thz rings as ASC, but the ring positions were switched. cyclo(–Ile–Oxz–D ‐Val–Thz–Ile–Thz–D ‐Val–Thz–) ( 3 ) and cyclo(–Ile–Thz–D ‐Val–Oxz–Ile–Thz–D ‐Val–Thz–) ( 4 ) contained one Oxz and three Thz rings within the molecule. All Oxz rings were substituted with Thz in cyclo(–Ile–Thz–D ‐Val–Thz–)2 ( 5 ). These analogues had new Oxz and Thz blocks forming the 24‐membered ring. Based on CD spectra and X‐ray diffraction analyses, the structures of all four analogues were classified as square ASC forms. But the structures of 2 and 5 differed from the original square form of 1 , and they showed no cytotoxicity. The structure of 3 was very similar to that of 1 , and 3 showed 10 times greater cytotoxicity than 1 . Although no definite structure of 4 was obtained, it showed three times greater cytotoxicity than 1 . It appears that the position and number of Oxz residues are essential determinants in the structure‐cytotoxicity relationship of ASC analogues. |
| |
| Keywords: | 1H NMR ascidiacyclamide CD spectrum crystal structure cytotoxicity oxazoline thiazole |
|
|
