In vitro and in vivo evaluation of select kahalalide F analogs with antitumor and antifungal activities

Kahalalide F (KF) and the regioisomer isoKF are novel anticancer drugs of marine origin and currently under clinical investigation. Here we report the synthesis of two new KF analogs with significant in vitro and in vivo antifungal and antitumor activities. The primary amine hydrogen of ornithine in...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2011-11, Vol.19 (22), p.6628-6632
Main Authors: Shilabin, Abbas Gholipour, Hamann, Mark T.
Format: Article
Language:English
Subjects:
amines
animal fibers
Animals
Anti-cancer
Anti-infective
anticarcinogenic activity
Antifungal activity
Antifungal Agents - chemistry
Antifungal Agents - pharmacology
antifungal properties
antineoplastic agents
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Antitumor activity
Antitumor agents
chemistry
Depsipeptides - chemistry
Depsipeptides - pharmacology
Drug Screening Assays, Antitumor
Fibers
Humans
Hydrogen
in vivo studies
Kahalalide F
Marine natural products
Mice
Mice, Nude
Microbial Sensitivity Tests
ornithine
Paclitaxel
screening
Structure-Activity Relationship
Toxicity
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Summary:Kahalalide F (KF) and the regioisomer isoKF are novel anticancer drugs of marine origin and currently under clinical investigation. Here we report the synthesis of two new KF analogs with significant in vitro and in vivo antifungal and antitumor activities. The primary amine hydrogen of ornithine in KF has been replaced with 4-fluoro-3-methylbenzyl and morpholin-4-yl-benzyl via reductive N-alkylation. The TGI of these analogs using the NCI-60 cell line screening revealed promising results when compared to paclitaxel. The result of in vivo hollow fiber and animal toxicity assays are presented.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2011.06.050