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Distributed Drug Discovery, Part 3: using D(3) methodology to synthesize analogs of an anti-melanoma compound.

Scott WL, Audu CO, Dage JL, Goodwin LA, Martynow JG, Platt LK, Smith JG, Strong AT, Wickizer K, Woerly EM, O'Donnell MJ - J Comb Chem (2009 Jan-Feb)

Bottom Line: This article reports the successful achievement of this goal.All compounds were made in duplicate, purified by silica gel chromatography, and characterized by NMR and LC/MS.As a continuing part of the Distributed Drug Discovery program, a virtual D(3) catalog based on this work was then enumerated and is made freely available to the global scientific community.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Chemical Biology, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana 46202-3274, USA. wscott@iupui.edu

ABSTRACT
For the successful implementation of Distributed Drug Discovery (D(3)) (outlined in the accompanying Perspective), students, in the course of their educational laboratories, must be able to reproducibly make new, high quality, molecules with potential for biological activity. This article reports the successful achievement of this goal. Using previously rehearsed alkylating agents, students in a second semester organic chemistry laboratory performed a solid-phase combinatorial chemistry experiment in which they made 38 new analogs of the most potent member of a class of antimelanoma compounds. All compounds were made in duplicate, purified by silica gel chromatography, and characterized by NMR and LC/MS. As a continuing part of the Distributed Drug Discovery program, a virtual D(3) catalog based on this work was then enumerated and is made freely available to the global scientific community.

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Compounds inducing apoptosis in a melanoma cell line.
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Related In: Results  -  Collection

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fig1: Compounds inducing apoptosis in a melanoma cell line.

Mentions: Our first virtual D3 catalog was reported in the previous paper.(2) It is now freely available to the global community for analysis by computational models appropriate for neglected diseases. While waiting for molecular targets to emerge from this process, a disease and class of target molecules was identified that would allow testing the capability of D3 methodologies to make new, high-quality, potentially biologically active molecules. In 2005 researchers at the University of Illinois reported the discovery, from a combinatorial library, of molecules that induced apoptosis in a melanoma cell line.3−5 The most potent molecule (IC50 = 0.5 μM) in their collection was 1 (from the R-isomer of phenylalanine). A close analog, 2, also showed significant activity (Figure 1).


Distributed Drug Discovery, Part 3: using D(3) methodology to synthesize analogs of an anti-melanoma compound.

Scott WL, Audu CO, Dage JL, Goodwin LA, Martynow JG, Platt LK, Smith JG, Strong AT, Wickizer K, Woerly EM, O'Donnell MJ - J Comb Chem (2009 Jan-Feb)

Compounds inducing apoptosis in a melanoma cell line.
© Copyright Policy - open-access - ccc-price
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2651688&req=5

fig1: Compounds inducing apoptosis in a melanoma cell line.
Mentions: Our first virtual D3 catalog was reported in the previous paper.(2) It is now freely available to the global community for analysis by computational models appropriate for neglected diseases. While waiting for molecular targets to emerge from this process, a disease and class of target molecules was identified that would allow testing the capability of D3 methodologies to make new, high-quality, potentially biologically active molecules. In 2005 researchers at the University of Illinois reported the discovery, from a combinatorial library, of molecules that induced apoptosis in a melanoma cell line.3−5 The most potent molecule (IC50 = 0.5 μM) in their collection was 1 (from the R-isomer of phenylalanine). A close analog, 2, also showed significant activity (Figure 1).

Bottom Line: This article reports the successful achievement of this goal.All compounds were made in duplicate, purified by silica gel chromatography, and characterized by NMR and LC/MS.As a continuing part of the Distributed Drug Discovery program, a virtual D(3) catalog based on this work was then enumerated and is made freely available to the global scientific community.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Chemical Biology, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana 46202-3274, USA. wscott@iupui.edu

ABSTRACT
For the successful implementation of Distributed Drug Discovery (D(3)) (outlined in the accompanying Perspective), students, in the course of their educational laboratories, must be able to reproducibly make new, high quality, molecules with potential for biological activity. This article reports the successful achievement of this goal. Using previously rehearsed alkylating agents, students in a second semester organic chemistry laboratory performed a solid-phase combinatorial chemistry experiment in which they made 38 new analogs of the most potent member of a class of antimelanoma compounds. All compounds were made in duplicate, purified by silica gel chromatography, and characterized by NMR and LC/MS. As a continuing part of the Distributed Drug Discovery program, a virtual D(3) catalog based on this work was then enumerated and is made freely available to the global scientific community.

Show MeSH
Related in: MedlinePlus