Synthesis and pharmacological evaluation of the novel pseudo-symmetrical tamoxifen derivatives as anti-tumor agents.
ABSTRACT Four pseudo-symmetrical tamoxifen derivatives, RID-B (13), RID-C (14), RID-D (15), and bis(dimethylaminophenetole) (16), were synthesized via the novel three-component coupling reaction, and the structure-activity relationships of these pseudo-symmetrical tamoxifen derivatives were examined. It was discovered that 13 and 16 strongly inhibit the viability of the HL-60 human acute promyelocytic leukemia cell line, whereas 14 possesses a medium activity against the same cell line and 15 has no effect on the cell viability. The global anti-tumor activity of 13-16 against a variety of human cancer cells was assessed using a panel of 39 human cancer cell lines (JFCR 39), and it was shown that RID-B (13) strongly inhibited the growth of several cancer cell lines at concentrations of less than 1 microM (at 0.38 microM for SF-539 [central nervous system], at 0.58 microM for HT-29 [colon], at 0.20 microM for DMS114 [lung], at 0.21 microM for LOX-IMVI [melanoma], and at 0.23 microM for MKN74 [stomach]).
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ABSTRACT: In a survey of nonpeptide noncovalent inhibitors of the human 20S proteasome, we found that a novel tamoxifen derivative, RID-F (compound 6), inhibits all three protease activities of the proteasome at submicromolar levels. Structure-activity relationship studies revealed that a RID-F analog (RID-F-S*4, compound 25) is the smallest derivative compound capable of inhibiting proteasome activity, with a potency similar to that of RID-F. Kinetic analyses of the inhibition mode and competition experiments involving biotin-belactosin A (a proteasome inhibitor) binding indicated that the RID-F derivatives interact with the protease subunits in a different manner. Culturing of human cells with these compounds resulted in accumulation of ubiquitinated proteins and induction of apoptosis. Thus, the RID-F derivatives may be useful lead chemicals for the generation of a new class of proteasome inhibitors.European Journal of Medicinal Chemistry 11/2013; 71C:290-305. · 3.43 Impact Factor
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ABSTRACT: In a previous work we have demonstrated the antimicrobial activity of ferrocenyl or phenyl derivatives of diphenyl butene series. This finding has opened a new area of applications of organometallic compounds. In order to improve these activities, we have synthesized new organic and organometallic diaryl butene compounds with different lengths of their amino chains. These new compounds, and also their ammonium salts, were tested against man pathogenic microorganisms Escherichia coli (ATCC 10536), Pseudomonas aeruginosa (ATCC 15442), Staphylococcus aureus (ATCC 6538) and Enterococcus hirae (ATCC 10541). It emerged from the tests that the Gram+ bacteria are more sensitive to the compounds than Gram-, and the compounds with 3 carbon amino chains have a better antimicrobial activity than the one having a chain of 2 or 4 carbons. The transformation of compounds to citrate salts was accompanied by a significant regression of antibacterial activity against Pseudomonas aeruginosa, for both organic and ferrocenic molecules. This resistance problem has been solved using hydrochlorides salts rather than citrates one.SpringerPlus 01/2013; 2:508.
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ABSTRACT: The crown gall induced in potato discs by Agrobacterium tumefaciens is becoming largely utilised in screening anti-tumor agents. The present work is showing that beet discs are more adequate for the anti-tumor screening test. In fact, maximal tumor induction was observed on beet discs (87.5%), followed by carrot discs (75%) and potato discs (68.5%). Beet discs present the most sensibility to crown gall disease with a fast expression of symptoms and more visible galls without any staining need. The beet discs bioassay was carried out by using some synthesized organometallics known for their antitumor activity in mammalian cells. We found significant crown gall inhibition (20.7% to 40.55%) of the tested compounds. Overall results supported that beet bioassay might be a potential prescreen system of anti-tumor molecules in mammalian cells.International journal of biomedical science : IJBS. 12/2013; 9(4):230-6.