Cancer cell lines inhibition derivatives

Table 7. Cancer Cell Lines Inhibited by Other 1,3-Diphenylpropane Derivates.

Sansalvamide A is an antineoplastic macrocyclic depsipeptide isolated from the marine fungus Fusarium by William Fenical in 1999. Studies have shown potent cytotoxicity against NCI s 60 cell line panel for the natural product and ten-fold inhibition over the depsipeptide for the pentapeptide derivative. A library of over 100 derivatives of the compound have been synthesized and the Structural Activity Relationships (SARs) show promising bio-potency against pancreatic, colon, breast, prostate and melanoma cancer cell-lines. Six derivatives show over 100-fold differential selectivity for cancer cell lines over normal cell lines and are over 100 times more active against pancreatic cancer cell lines than compounds used clinically to treat these cancers (e.g., 5-FU). Through use of inhibition assays and analysis of trends emerge that can be used to modify the scaffold to produce more potent compounds. 

Barbieri and coworkers have studied the antiproliferative activity and interactions of cell-cycle-related proteins utilizing the organotin compoimd containing a quinolizidine derivative. The particular compoimd studied was triethyltin lupinylsulfide hydrochloride (5). In early tests this compound was found to show good cancer cell line inhibition, so more extensive studies were undertaken. 

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). 

Another peculiarity of the study is that the use of a biological system has allowed the authors to hypothesize a possible mechanism of action of the leachate as a mixture, hypothesis that could have been drafted on the basis of the only knowledge derived by chemical analysis. Researchers suggest that leachate inhibits cell proliferation at low doses probably inducing a reversible cell cycle arrest that becomes irreversible at high doses, probably due to leachate-induced oxidative stress. This activity is mainly due to the chemical compounds extracted in the aqueous phase. Similar effects were noticed by previous investigations on other human cells (human peripheral blood lymphocytes and a human breast cancer cell line, MCF-7) [31, 32], supporting the hypothesis that cells that survive the initial insult from leachate constituents maintains the potential to proliferate until the effects on cell metabolism lead to death. 

Cell lines established from human liver cancer cells can be derived from primary hepatocellular carcinoma or hepatoblastoma cells [10]. For example, the well known HepG2 fine was derived from hepatoblastoma cells. Such cells can be employed effectively if the function of normal liver cells has been highly preserved. In practice, however, such cells contain a high proportion of abnormal genetic component, which inhibits their ability to express normal protein synthesis and enzyme activity. Potential problems, such as the loss of liver specific functions and the possibifity of metastasis, which could arise from the use of hepatoma cells have not yet been satisfactorily discussed [13]. 

The collection procedure itself is straightforward. After cataloguing and identification, 1-2 kg of the plant material is dried, or stored in alcohol and brought back to the lab. The plant material is crushed and extracted with various solvents (most plant-derived bioactive molecules are low molecular mass substances, soluble in organic solvents of varying polarity). After removal of the solvent, the extracts are screened for desirable biological activities (e.g. inhibition of microbial growth, selective toxicity towards various human cancer cell lines, etc.). 

Recently discovered antitumor monocyclic and bicyclic (3-lactam systems [40-42] are, in general, in good agreement with the phenomenon of azetidin-2-one pharmacophore of inexhaustible pharmacological potential on account of the specific ability of its numerous derivatives to inhibit not only bacterial transpeptidase, but also mammalian serin and cystein proteases [43]. As a measure of cytotoxicity, some compounds have been assayed against nine human cancer cell lines. 

Pec MK, Moser-Thier K, Fernandez JJ, Souto ML, Kubista E (1999) Growth Inhibition by Dehydrothyrsiferol - A Non-Pgp Modulator, Derived from a Marine Red Alga - in Human Breast Cancer Cell Lines. Int J Oncol 14 739... 

Vaclavikova et al. [216] have investigated the effect of 13 flavonoid derivatives—aurones, chalcones, flavones, flavonols, chromones, and isoflavones—on 14 C-paclitaxel transport in two human breast cancer cell lines, the doxorubicin-resistant NCI/ADR-RES and sensitive MDA-MB-435. The compounds with known binding affinity toward the NBD of P-gp were selected. The four aurones studied most effectively inhibited P-gp-related transport in the resistant fine in comparison with other groups of flavonoids. The aurones also most effectively increased the intracellular accumulation of paclitaxel and decreased its efflux. The results obtained did not always correlate with the binding of flavonoid derivatives to P-gp, so this indicated that the binding was not the only factor influencing the transport of paclitaxel. The different aspects of inhibition of P-gp by polyphenols was recently reviewed by Kitagawa [212],... 

Agelastatins are highly bioactive derivatives, possessing activity against several cancer cell lines at nanomolar concentrations, although the mechanism of this potent action has not yet been elucidated [93]. In addition, agelastatin A (62) inhibits... 

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