Cell growth inhibitory activity

More recently, some closely related analogs of phakellins have been obtained. Firstly, the phakellins 43 and 44, enantiomeric to 41 and 42, respectively, were obtained from Pseudaxynissa cantharella [51] later, the 7-N-methylphakellins 45 and 46 were isolated from an Agelas sp. [72], and phakellistatin (47) from Phakellia mauritiana [73]. This last compound was reported to exhibit potent cell growth inhibitory activity against a variety of human cancer cell lines (ED50 from 0.3 to 4.0 p,M) [73]. 

Halichondrin B (205) has received much attention due to its extraordinary in vitro and in vivo antitumor activity (O Fig. 19). Recently, structurally simplified macrocyclic ketone analogs of halichondrin B (205) were found to retain the potent cell growth inhibitory activity in vitro, stability in mouse serum, and in vivo efficacy of the natural product [108,109,110]. 

The bis-steroidal alkaloids cephalostatins 1-15 (11-25) (24-30) and rit-terazines A-M (26-38) (31-33) isolated from the marine worm Cephalodis-cus gilchristi and the tunicate Ritterella tokioka, respectively, also exhibit powerful cell growth inhibitory activity against a number of cell lines. 

To date, several naturally occurring cyclic heptapeptides have been reported, such as ilamycin Bi (213), a dolastatin 3 analog (214), cycloheptasar-cosine (215), rhizonin A (216), evolidine (217), hymenamide (218), and phakellistatin (219). The presence of cyclic heptapeptides is very rare in nature. Yunnanins A, C, and D showed cell-growth-inhibitory activity... 

Dichotomins A, B, C, and E showed cell growth inhibitory activities against p388 lymphocytic leukemia cells (IC50 A 2.5 /xg/ml B 3.5 pg/ml C 5.0 /xg/ml E 2.0 jug/ml) dichotomin D did not. The amino acid sequences of dichotomins A, B, and C are the same, except at residue 5 (dichotomins A Val B Thr C Ala). The cyclic pentapeptide, dichotomin E, contains a sequence (Tyr-Ala-Phe) similar to the Phe-Leu-Tyr sequence present in dichotomins A, B, and C, the central aliphatic amino acid of which is sandwiched between two aromatic amino acids. This inhibitory activity may be due to the sequencing and/or conformation of these dichotomins. 

New proline-rich cyclic nanapeptides, cycloleonuripeptides A-D (344-347), showing cell growth inhibitory activity, have been isolated from the fruits of Leonurus heterophyllus (248). Their structures and conformations were elucidated by extensive 2D-NMR (248) and X-ray crystallographic analysis (249), and by distance geometry calculations (250) (Fig. 51). 

The dihydropyranethylene 64, which a synthetic intermediate of pancratistatin that exhibits a high level of in vitro and in vivo cancer cell growth inhibitory activity and antiviral activity was rearranged to the cix-disubstituted cydohexene 65 as a single isomer (Eq. 3.1.42) [53]. This rearrangement proceeds through a boat-Hke transition state of the cydohexene [54]. 

The cell growth inhibitory activity, antitumor activity, and toxicity of M-16 and M-18, the major metabolites of a new mitomycin C (MMC) derivative, KW-2149 (124), in both mice and humans were compared with those of KW-2149 and MMC in vitro and in vivo. The growth inhibitory activity of M-18, a symmetric disulfide dimer, active against human uterine cervix carcinoma HeLa S3 cells was almost equivalent to that of KW-2149, and their IC50 values were about tenfold smaller than that of MMC. The activity of M-16, a Me sulfide form, was almost equivalent to that of MMC. 

Suzuki, M., Watanabe, K., Fujiwara, S Kuruzawa, T, Wakabayashi, T Tsuzuki, M., Igudii, K., and Yamori, T. (2003) Isolation of peridinin-related norcarotenoids with cell growth-inhibitory activity from the cultured dinoflagellate of Symbiodinium sp., a symbiont of the Okinawan soft coral Clavularia viridis, and analysis of fatty acids of the dinoflagellate. Chem. Pharm. Bull., 51, 724-727. 

Smitii, A,B, III, Razler, T.M., Meis, R.M., and Pettit, G.R. (2008) Synthesis and biological evaluation of phorboxazole congeners leading to the discovery and preparative-scale of (-F)-chloro-phorboxazole A possessing picomolar human solid tumor cell growth inhibitory activity. J. Org. Chem., 73, 1201-1208. 

Smith, A.B., Lin, Q.Y, Pettit, G.R., Chapuis, J.C., and Schmidt, J.M. (1998) Synthesis and in vitro cancer cell growth inhibitory activity of monocyclic model compounds containing spongistatin triene side-chains. Bioorg. Med. Chem. Lett., 8, 567-568. 

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