Benzo antitumor

Recent advances on antitumor-active benzo[c]phenanthridine alkaloids 99H(50)627. 

Fagaronine and nitidine from Zanthoxylum species represent two of the more potent antitumor benzo[c]phenanthridines of Rutaceae. Both of these alkaloids have been shown to inhibit the enzymatic activity of topoisomerase in a way similar to camptothecin (28,29). It would be interesting to learn whether further study on Z. ailanthoid.es Sieb. Zucc. discloses any benzo[c]phenanthridine alkaloid of anti-neoplastic value. 

Michel S, Gaslonde T, Tillequin F. (2004) Benzo[b]acronycine derivatives A novel class of antitumor agents. Eur J Med Chem 39 649-655. 

Although there are preliminary data supporting the antitumoral activity of quercetin, the most common flavonoid, in humans in the course of a Phase I clinical trial [189], direct evidence of the anticancer effect of flavonoids is derived almost exclusively from studies performed in animal models as well as studies performed on cultured cell lines, Fig. (2). Most animal studies on gastrointestinal cancer have focused on colon cancer using the azoxymethane (AOM) model in rats or mice [190-197]. There are also available reports on models of cancer of the stomach (induced by benzo[a]pyrene [198] or N-methyl-N-nitro-N-nitro so guanidine [199]), oesophagus (N-methyl-N-amylnitrosamine [200]), and the tongue/oral cavity (methyl-(acetoxymethyl)-nitrosamine [198], 7,12-dimethyl-... 

Anderson RF, ShindeSS, Elay MP, GamageSA, Denny WA (2003b) Activation of 3-amino-1,2,4-benzo-triazine 1,4-dioxide antitumor agents to oxidizing species following their one-electron reduction. J Am Chem Soc 125 748-756... 

Many derivatives containing the benzo-4,8-diazaazulene skeleton 185 show pronounced antitumor activities. Synthetic work in this field has been reported (85H1603). 

Clinical applications of the first phenothiazines date back to 1940 [14]. The antineoplastic properties of these agents emerged almost simultaneously. Certain phenothiazines and benzo[a]phenothiazines possess an inhibitory action for the growth of cancer cells. Benzo[a]phenothiazines revealed remarkable antitumor activity against human myelogenous leukemia cell lines. This is a distinctive property of benzo[a]phenothiazines. Such an action was possibly reflected due to the relationship between anticancer activity and 77-electron density of benzo[a] phneothiazines [73]. 

Motohashi N, Kurihara T, Satoh K, Sakagami H, Mucsi L, Pusztai R, Szabo M, Molnar J (1999) Antitumor activity of benzo[n]phenothiazines. Anticancer Res 19 1837— 1842... 

Kurihara T, Motohashi N, Gui-Lin Pang, Higano M, Kiguchi K, Molnar J (1996) Correlation between topological resonance energy of methyl-substituted Benz[c] acridines, Benzo [a] phenothiazines and Chrysenes, and their carcinogenic or antitumor ac-tivites. Anti cancer Res 16 2757-2766... 

A recent study on the reactivity of the parent benzo-l,2-dithiolan-3-one 1-oxide 79a (R = R = H) and o- and /i-substituted derivatives 79b-g with -propyl thiol in acetone/water mixture (7/3) was prompted (Table 5) by the observation that the DNA-cleaving activity and antitumor activity of leinamycin 5 depends, in part <2005JOC6968>, on initial thiol attack on its l,3-dioxo-l,2-dithiolane functionality. Experimental results have proved that the presence of chlorine as an electron acceptor in the /i ra-position relative to the sulfmyl sulfur S-1 of precursor 79e and ortho-substituents with lone electron pairs in the case of precursors 79b and 79d are responsible for increased product formation of polysulfanes 80 and 81. A rationale in terms of substituent effects, operating through-space and through-bond of the intermediates a and b, respectively, was suggested. In other words, the reaction is favored by ortho-substituents with lone pair electrons next to the dithiolanone-oxide (S-1) reaction center or a decrease of the electron density at the /i ra-position. 

Melkova, Z. (1984). Utilization of the Index of Molecular Connectivity in the Study of Antitumor Activity of a Group of Benzo(c)fluorene Derivatives. Cesk.Farm., 33,107. 

Benzo[c]phenanthridine alkaloids, chemistry and antitumor activity of ... 

Melkova, Z. (1984) Utilization of the index of molecular connectivity in the study of antitumor activity of a group of benzo[c]fiuorene derivatives. Ceskoslov. Farm., 33, 107-111. 

New bisnaphthyridines 352 and 353 containing the 5-amino-2,4-dime-thylbenzo[Z>][l,8]naphthyridine or benzo[Z>][l,8]naphthyridone chromophores were synthesized in a phase-transfer system by the reaction of aminobenzonaphthyridine 354 or dihydrobenzonaphthyridone 355 with alkylene dibromides (2000JHC1289). Such bisintercalates are of interest as potential antitumor drugs. 

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