Total synthesis as a resource in drug discovery: The first in vivo evaluation of panaxytriol and its derivatives Journal Article
| Authors: | Yun, H.; Chou, T. C.; Dong, H.; Tian, Y.; Li, Y. M.; Danishefsky, S. J. |
| Article Title: | Total synthesis as a resource in drug discovery: The first in vivo evaluation of panaxytriol and its derivatives |
| Abstract: | We have conducted key preliminary studies into the in vitro and in vivo cytotoxicity of panaxytriol. Through total synthesis, we prepared and evaluated several synthetic panaxytriol analogues, each of which exhibited enhanced cytotoxicity relative to the natural product. Consequently, we have begun to chart the first in vitro SAR map for the compound, which suggests that the C 3 hydroxyl functionality is not critical for biological activity and that, in fact, engagement of the C 9-C 10 diol as an acetonide actually leads to notably enhanced cytotoxicity. Furthermore, through in vivo investigations, we demonstrated that panaxytriol and panaxytriol acetonide (12) moderately suppress tumor growth with little or no toxicity. Finally, preliminary in vitro evaluation of panaxytriol indicates that it possesses neurotrophic activity. © 2005 American Chemical Society. |
| Keywords: | controlled study; unclassified drug; human cell; nonhuman; antineoplastic agents; animal cell; mouse; cell survival; animal experiment; animal model; in vivo study; antineoplastic activity; cancer cell culture; drug potency; in vitro study; drug screening; drug screening assays, antitumor; cell line, tumor; drug synthesis; structure activity relation; structure-activity relationship; vinblastine; cancer inhibition; biological activity; tumors; rat; drug cytotoxicity; natural product; ic 50; inhibitory concentration 50; reaction analysis; synthesis (chemical); natural products; hydroxylation; alkynes; hydroxyl group; drug conformation; drug products; panaxytriol; panaxytriol acetonide; neurotropism; enediynes; fatty alcohols; cytotoxixity |
| Journal Title: | Journal of Organic Chemistry |
| Volume: | 70 |
| Issue: | 25 |
| ISSN: | 0022-3263 |
| Publisher: | American Chemical Society |
| Date Published: | 2005-12-09 |
| Start Page: | 10375 |
| End Page: | 10380 |
| Language: | English |
| DOI: | 10.1021/jo0515475 |
| PUBMED: | 16323847 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 27" - "Export Date: 24 October 2012" - "CODEN: JOCEA" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
-
33Dong -
539Danishefsky -
133Li -
319Chou -
16
Tian
Related MSK Work