Cytotoxicity against cancer cell lines

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. 

Cytotoxicity of Natural Triterpene QMs Against 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. 

An other example of Salvia quinone is salvicine, a structurally modified diterpenoid quinone derived from Salvia prionitis, which is cytotoxic against multidrug-resistant cancer cell lines of topoisomerase II inhibition by trapping the DNA-topoisomerase II complex (49). 

A variety of substituted dibenzo-fused derivatives 126 have been prepared for evaluation of their biological activities. The synthesis of these compounds involves the reaction of o-acylanilines with pyrroloindolones 125, in boiling butan-l-ol with pyridinium />-toluenesulfonate as catalyst (Equation 8). Compounds such as 126 which contain the benzo[5,6]pyrrolizino[l,2-A]quinoline skeleton exhibit cytotoxicity against several cancer cell lines <2004BML2363>. 

Multicomponent reactions (MCRs) have been known to produce highly complex and diverse structures [76]. There is a considerable interest in the application of new multicomponent reactions to access biologically relevant molecules [77,78] and natural products [79]. A recent report has disclosed multicomponent Passerini and Ugi reactions to produce, rapid and efficiently, a library of redox-active selenium and tellurium compounds [80]. The compounds showed promising cytotoxicity against several cancer cell lines. 

Fig. 8. Complex 7 is nontoxic in the dark, yet shows remarkable cytotoxicity with irradiation against several cancer cell lines cisplatin is included for comparison. Data from Ref. (35).

Synthetic a-carbolines have also attracted interest as antitumor agents. For example, Chen and coworkers [97] prepared a series of indolo[2,3-fr] quinoline derivatives, the most active of which was 154, which had a mean GI50 value against three cancer cell lines of 0.78 iM. This compound was prepared by methylation of 153 with dimethyl sulfate (Fig. 43), and was isolated in 12% yield, along with isomeric 155, which was isolated in 40% yield, but had significantly lower cytotoxicity. Precursor 153 itself was found to be inactive. 

Novel macrocyclic and open-chain taxoid mimicking compounds were synthesized. Two of these, compounds 283 and 284, were found to possess cytotoxicity with micromolar level IC50 values against human breast cancer cell lines <2004BML3491>. 

A series e t-kaurane diterpenoids isolated from Sideritis species were tested against A2780 ovarian cancer cell lines, and 7-e/>/candicandiol (Fig. 6.6) showed the highest cytotoxic potential with ICj , = 9.0 pg/mL, and sidol followed it (ICj , = 15.6 pg/mL). 

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]. 

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