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Design, synthesis and evaluation of new marine alkaloid-derived pentacyclic structures with anti-tumoral potency.

Boucle S, Melin C, Clastre M, Guillard J - Mar Drugs (2015)

Bottom Line: This work describes the synthesis and biological evaluation of a new heterocyclic hybrid derived from the ellipticine and the marine alkaloid makaluvamine A.The analysis by electrophoresis shows that the pentacycle 12 inhibits the topoisomerase II like doxorubicine at 100 µM.Compound 9 was found to have an interesting profile, having a cytotoxicity of 15, 15, 15 and 10 μM against Caco-2, HCT-116, Pc-3 and NCI cell lines respectively, without any noticeable toxicity against human fibroblast.

View Article: PubMed Central - PubMed

Affiliation: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, and Veterans Affairs Medical Center, Decatur, GA 30033, USA. s.boucle@hotmail.fr.

ABSTRACT
This work describes the synthesis and biological evaluation of a new heterocyclic hybrid derived from the ellipticine and the marine alkaloid makaluvamine A. Pyridoquinoxalinedione 12 was obtained in seven steps with 6.5% overall yield. 12 and its intermediates 1-11 were evaluated for their in vitro cytotoxic activity against different cancer cell lines and tested for their inhibitory activity against the human DNA topoisomerase II. The analysis by electrophoresis shows that the pentacycle 12 inhibits the topoisomerase II like doxorubicine at 100 µM. Compound 9 was found to have an interesting profile, having a cytotoxicity of 15, 15, 15 and 10 μM against Caco-2, HCT-116, Pc-3 and NCI cell lines respectively, without any noticeable toxicity against human fibroblast.

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Synthesis of the aminopyridiniminoquinone 3. (a): Bromoacetylbromide, THF, Et3N, reflux, 2 days, 65%; (b): dimethylacryloylchloride, pyridine, 2h, 78%; (c): (i) AlCl3, DCM, 24 h, 83%; (d): (i) HNO3, DCM/DMF, 24 h, 42%; (ii) H2, Pd/C, DMF/DMSO, 18 h, 70%; (e): BH3/THF, THF, 2 h, reflux, 81%.
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marinedrugs-13-00655-f004: Synthesis of the aminopyridiniminoquinone 3. (a): Bromoacetylbromide, THF, Et3N, reflux, 2 days, 65%; (b): dimethylacryloylchloride, pyridine, 2h, 78%; (c): (i) AlCl3, DCM, 24 h, 83%; (d): (i) HNO3, DCM/DMF, 24 h, 42%; (ii) H2, Pd/C, DMF/DMSO, 18 h, 70%; (e): BH3/THF, THF, 2 h, reflux, 81%.


Design, synthesis and evaluation of new marine alkaloid-derived pentacyclic structures with anti-tumoral potency.

Boucle S, Melin C, Clastre M, Guillard J - Mar Drugs (2015)

Synthesis of the aminopyridiniminoquinone 3. (a): Bromoacetylbromide, THF, Et3N, reflux, 2 days, 65%; (b): dimethylacryloylchloride, pyridine, 2h, 78%; (c): (i) AlCl3, DCM, 24 h, 83%; (d): (i) HNO3, DCM/DMF, 24 h, 42%; (ii) H2, Pd/C, DMF/DMSO, 18 h, 70%; (e): BH3/THF, THF, 2 h, reflux, 81%.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4306956&req=5

marinedrugs-13-00655-f004: Synthesis of the aminopyridiniminoquinone 3. (a): Bromoacetylbromide, THF, Et3N, reflux, 2 days, 65%; (b): dimethylacryloylchloride, pyridine, 2h, 78%; (c): (i) AlCl3, DCM, 24 h, 83%; (d): (i) HNO3, DCM/DMF, 24 h, 42%; (ii) H2, Pd/C, DMF/DMSO, 18 h, 70%; (e): BH3/THF, THF, 2 h, reflux, 81%.
Bottom Line: This work describes the synthesis and biological evaluation of a new heterocyclic hybrid derived from the ellipticine and the marine alkaloid makaluvamine A.The analysis by electrophoresis shows that the pentacycle 12 inhibits the topoisomerase II like doxorubicine at 100 µM.Compound 9 was found to have an interesting profile, having a cytotoxicity of 15, 15, 15 and 10 μM against Caco-2, HCT-116, Pc-3 and NCI cell lines respectively, without any noticeable toxicity against human fibroblast.

View Article: PubMed Central - PubMed

Affiliation: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, and Veterans Affairs Medical Center, Decatur, GA 30033, USA. s.boucle@hotmail.fr.

ABSTRACT
This work describes the synthesis and biological evaluation of a new heterocyclic hybrid derived from the ellipticine and the marine alkaloid makaluvamine A. Pyridoquinoxalinedione 12 was obtained in seven steps with 6.5% overall yield. 12 and its intermediates 1-11 were evaluated for their in vitro cytotoxic activity against different cancer cell lines and tested for their inhibitory activity against the human DNA topoisomerase II. The analysis by electrophoresis shows that the pentacycle 12 inhibits the topoisomerase II like doxorubicine at 100 µM. Compound 9 was found to have an interesting profile, having a cytotoxicity of 15, 15, 15 and 10 μM against Caco-2, HCT-116, Pc-3 and NCI cell lines respectively, without any noticeable toxicity against human fibroblast.

Show MeSH
Related in: MedlinePlus