Cytotoxic activity against

Dysidazirine 130 was isolated by Ireland in 1988 from a Fijian sample of the marine sponge Dysidea fragilis [194] as the major lipophilic component of the sponge and was shown to possess cytotoxic activity against L1210 cells, as well as... 

TNF was originally identified because of its cytotoxic activity against some tumor cell lines and its ability to induce hemorrhagic necrosis of solid tumors in various animal models. However, the clinical use of TNF as an anticancer drug has been so far limited by its severe cardiovascular side effects. Therefore, TNF treatment is limited to regional and local administration of high doses of TNF, often in combination with chemotherapy, as accomplished in isolated limb and isolated hepatic perfusion (ILP and IHP, respectively) [5]. In the case of ILP, typically metastases are treated, patients benefit from this procedure by salvage of limbs from a loss by amputation. 

There is also evidence that individual chlorophyll derivatives exhibit cytostatic and cytotoxic activities against tumor cells. Studies have been started on electronic structures, in particular the electronic state of the phorphyrin macrocycle, and progress in this area is expected regarding photodynamic therapy for tumors, since the strong absorption of hght in the visible region is effective for laser excitation. Nevertheless, httle is known to date about the influences of peripheral groups on the electronic state of the macrocycle n system in chlorophyll derivatives. ... 

Some of the [Au(N,0)Cl2] derivatives, namely 58a, 59a and 59b, which have been tested for cytotoxic activity against various human tumor cell lines, have shown significant effects [144]. Compound 57 is a potential alternative to dimethylgold (III) P diketonates and can be used as a starting material for gold coatings by the CVD method [140]. Recent studies have shown that the long-term stability of these... 

Haliclonacyclamine F (25), arenosclerin D (26), and arenosclerin E (27) have been recently isolated from the sponge Pachychalina alcaloidifera endemic in Brazil [26]. The alkaloids 25-27 were isolated from the cytotoxic, antibiotic, and antituberculosis MeOH crude extract of P. alcaloidifera by a series of separations on silica-gel and cyanopropyl-bonded silica-gel columns. The structures of compounds 25-27 were established by the same approach employed for the structural elucidation of haliclonacyclamine E (13) and arenosclerins A-C (14-16) [18], as well as by comparison with NMR data for this last series of alkaloids. The alkaloids 25-27 displayed moderate cytotoxic activity against SF295 (human CNS), MDA-MB435 (human breast), HCT8 (colon), and HL60 (leukemia) cancer cell lines. 

Guerrero, I. C. Andres, L. S. Leon, L. G. Machin, R. P. Padron, J. M. Luis, J. G. Delgadillo, J. Abietane diterpenoids from Salvia pachyphylla and S. clevelandii with cytotoxic activity against human cancer cell lines. J. Nat. Prod. 2006, 69, 1803-1805. 

The pyrrolonaphthyridines 208 and 209 can be prepared from rearrangement of the pentacycle 207 upon treatment with trifluoroacetic acid (TFA) (Scheme 52). These products are of interest as they have the same structural skeleton as the indole alkaloid (—)-goniomitine, isolated from the root bark of Gonioma Malagasy <1995JOC3282>. Compound 208 has since been used in the synthesis of further derivatives which show cytotoxic activity against leukemia cells <2001BML79>. 

Among almost 70 plant extracts (Table 6.5), seven-eight plants were found potential cytotoxic active, and their extracts were subjected for fractionation and isolation of pure compounds, and then over 300 fractions and 35 pure compounds were searched for ovarian cytotoxic activity against A2780 human ovarian cell lines. 

A compound of a very similar structure is phenazinomycin (67), which has been isolated from mycelial extracts of Streptomyces sp. WK-2057 by Omura et al. [69]. This compound possesses in vivo antitumor activity against experimental murine tumor cells and cytotoxic activity against adriamycin-resistant... 

The dimeric carbazole alkaloids often occur along with the corresponding monomeric carbazoles in terrestrial plants [7,62] (Scheme 7). Clausenamine-A was obtained by Wu from the stem bark of Clausena excavata [63]. Clausen-amine-A and its synthetic analogs, like bis(O-demethylmurrayafoline-A), show cytotoxic activities against diverse human cancer cell lines [64] and exhibit moderate antimalarial activity [65,66]. Furukawa isolated l,r-bis(2-hy-droxy-3-methylcarbazole) and bismurrayaquinone-A, the first dimeric car-bazolequinone alkaloid found in nature, from Murraya koenigii [67]. 

Recently, Turner et al. described the synthesis of the alkaloid (R)-(-t-)-crispine A, which shows cytotoxic activity against HeLa human cancer cell lines, using in the final step a deracemization procedure with the combination of an enantioselective amine oxidase obtained by directed evolution methods and a chemical non-selective reducing agent (Scheme 10.20) [48]. 

In 2002, Munro et al. reported the isolation of coproverdine (271) from a New Zealand Ascidian. The name of this isolate was derived from the descriptor attached to the voucher specimen (green sheep-shit-like in appearance), hence coproverdine copro Greek dung, ovis Latin sheep, verde Latin green). This alkaloid was isolated from Nature in optically active form [a]p — 8.0 (c 0.36, EtOH). However, the absolute configuration was not assigned. Coproverdine showed cytotoxic activity against a variety of murine and human tumor cell lines (240). 

In 1984, Giibble et al. reported for the first time a novel l,10-bis-(6-methyl-5H-benzo[fc]carbazol-ll-yl)decane (469) which has potential bifunctional nucleic acid intercalating properties (406). To function as anti-tumor active drugs, one of the most important cytostatic mechanisms of action of coplanar annelated polycyclic compounds is their intercalation with DNA (405). Ten years later, Kucklander et al. studied a series of 5H-benzo[ 7]carbazole quinone derivatives for their cytotoxic activity against colon and lung cancer cells, and found that the heteroannelated 5H-benzo[ 7]carbazole quinone derivative 470 was the most active among the various analogs (407) (Scheme 4.2). 

Several cycles of treatment may be necessary to achieve a substantial reduction in tumor size. The chemotherapeutic regimen, especially when one is dealing with large, solid tumors, probably should include agents that have cytotoxic activity against resting cells. 

Keenamide A is another novel cytotoxic cyclic hexapeptide isolated from a marine mollusk (Pleurobranchus forskalii Fig. 5.2 Wesson and Hamann, 1996). Keenamide A exhibited significant activity against the P-388, A-549, MEL-20, and HT-29 tumor cell lines. New classes of anticancer drug candidates isolated from marine organisms have been shown to possess powerful cytotoxic activity against multiple tumor types. 

Betulinic acid (50) Selective cytotoxic activity against melanoma cell lines1 [46]... 

Cytotoxic activity against human oral squamous cell carcinoma (HSC-2)... 

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