- New Hybrids Derived from Podophyllic Aldehyde and Diterpenylhydroquinones with Selectivity toward Osteosarcoma Cells
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A new family of molecular hybrids, between cyclolignans related to podophyllic aldehyde and several diterpenylnaphthohydroquinones (DNHQ), was prepared and its biological activity evaluated in several human solid tumor cell lines, which are representative of the most prevalent solid tumors in the Western world. Both cyclolignan and quinone fragments were linked through aliphatic or aromatic spacers. The new hybrid family was evaluated for its cytotoxicity, and it was found that the hybrids were several times more potent against the osteosarcoma cell line MG-63 than against MCF-7 and HT-29 cell lines. The presence of an aromatic ring in the linker gave the most potent and selective agent, improving the cytotoxicity of the parent compounds. Cell cycle studies demonstrated that this hybrid induces a strong and rapid apoptotic effect and arrests cells at the G2/M phase of the cell cycle, in the same way that the parent compound podophyllic aldehyde does.
- Hernández, ángela P.,Díez, Paula,García, Pablo A.,Miguel Del Corral, José M.,Pérez-Andrés, Martín,Díez, David,San Feliciano, Arturo,Fuentes, Manuel,Castro, Ma ángeles
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- Synthesis and biological evaluation of new podophyllic aldehyde derivatives with cytotoxic and apoptosis-inducing activities
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Several series of nonlactonic podophyllic aldehyde analogues were prepared and evaluated against several human tumor cell lines. They had different combinations of aldehyde, imine, amine, ester, and amide functions at C-9 and C-9′ of the cyclolignan skeleton. All the compounds synthesized showed cytotoxicity levels in the μM range and below. Within the new series tested, compounds having an aldehyde or imine at C-9 and an ester at C-9′ were the most potent, with GI50 values in the nM range, some of them being several times more potent against HT-29 and A-549 carcinoma than against MB-231 melanoma cells. Cell cycle studies and analysis of the microtubule-disrupting capacity have demonstrated the existence of two different mechanisms of cell death induction for compounds with closely related structures.
- Castro, Ma. ángeles,Miguel Del Corral, José Ma.,García, Pablo A.,Rojo, Ma. Victoria,De La Iglesia-Vicente, Janis,Mollinedo, Faustino,Cuevas, Carmen,San Feliciano, Arturo
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experimental part
p. 983 - 993
(2010/07/16)
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- Preparation and cytotoxicity of podophyllotoxin derivatives lacking the lactone ring
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Several cyclolignans lacking of the Iactone moiety can easily be prepared from naturally occurring lignans such as podophyllotoxin and deoxypodophyllotoxin by simple chemical transformations. Their cytotoxicity has been studied in four tumoral cell lines. Most of the compounds show similar effects in all the neoplastic systems tested, except the 3 aldehyde 9 (methyl 9-deoxy-9-oxo-α-apopicropodophyllate) and the hydrazones 16 and 17 which show a highly selective cytotoxicity towards HT-29 human colon carcinoma. Additionally, several molecular modeling studies have been done with aldehyde 9 and the correspnding saturated aldehyde 13 in comparison with podophyllotoxin.
- Gordaliza, Marina,Castro, M. Angeles,Miguel del Corral, Jose M.,Lopez-Vazquez, M. Luisa,Garcia, Pablo A.,Feliciano, Arturo San,Garcia-Gravalos, M. Dolores,Broughton, Howard
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p. 15743 - 15760
(2007/10/03)
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- Immunosuppressive cyclolignans
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The immunosuppressive activity of several lactonic, nonlactonic, and heterocycle-fused cyclolignans has been demonstrated for the first time by use of a T-cell-mediated immune response. Of the compounds tested, 4'- demethyldeoxypodophyllotoxin (8), β-apopicropodophyllin (6), and the isoxazoline-fused cyclolignan 15 are the most potent with respect to their suppression of activated splenocytes.
- Gordaliza, Marina,Faircloth, Glynn T.,Castro, Ma. Angeles,Miguel Del Corral, José M.,López-Vázquez, Ma. Luisa,San Feliciano, Arturo
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p. 2865 - 2868
(2007/10/03)
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- Comprehensive Synthetic Route to Eight Diastereomeric Podophyllum Lignans
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An oxabicyclo compound, 9, prepared in 47percent yield through an isobenzofuran intermediate was converted with excellent regio- and stereocontrol to eight (+/-)-lignan lactones of the podophyllotoxin series.One of the eight, epiisopicropodophyllin, 36, t
- Forsey, Steven P.,Rajapaksa, Dayananda,Taylor, Nicholas J.,Rodrigo, Russell
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p. 4280 - 4290
(2007/10/02)
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- TOTAL SYNTHESIS OF (+/-)-PODOPHYLLOTOXIN AND (+/-)-EPIPODOPHYLLOTOXIN
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A novel approach to (+/-)-epipodophyllotoxin (2c) and hence also to (+/-)-podophyllotoxin (1c) is described, involving as a key-step the stereoselective ring closure of the TMS-ester derived from 17a to the tetralin derivative 30c with mesyl chloride.
- Eyken, J. Van der,Clercq, P. de,Vandewalle, M.
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p. 4297 - 4308
(2007/10/02)
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- TOTAL SYNTHESIS OF (+/-)-PODOPHYLLOTOXIN AND (+/-)-EPIPODOPHYLLOTOXIN.
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A novel approach to (+/-)-epipodophyllotoxin (2) and hence also (+/-)-podophyllotoxin (1) is described, involving as a key-step the stereoselective ring closure of the TMS-ester derived from 14a to the tetralin derivative 15 with mesyl chloride.
- Eycken, J. Van der,Clercq, P. De,Vandewalle, M.
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p. 3871 - 3874
(2007/10/02)
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