Identification and Synthesis of Mycalol Analogues with Improved Potency against Anaplastic Thyroid Carcinoma Cell Lines

Cutignano, Adele ; Seetharamsingh, B. ; D’Angelo, Daniela ; Nuzzo, Genoveffa ; Khairnar, Pankaj V. ; Fusco, Alfredo ; Reddy, D. Srinivasa ; Fontana, Angelo (2017) Identification and Synthesis of Mycalol Analogues with Improved Potency against Anaplastic Thyroid Carcinoma Cell Lines Journal of Natural Products, 80 (4). pp. 1125-1133. ISSN 0163-3864

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Official URL: http://doi.org/10.1021/acs.jnatprod.7b00043

Related URL: http://dx.doi.org/10.1021/acs.jnatprod.7b00043

Abstract

The marine metabolite mycalol (1) has a specific inhibitory activity on cells of anaplastic thyroid carcinoma (ATC), a very aggressive and rare cancer that does not have effective conventional therapy. In this study, we describe six new related analogues (2–7) that differ in the length of the terminal alkyl residue and the presence of acetate or 3S-hydroxybutyrate (3S)-3HB as a substituent at C-19. Despite the structural analogies, some of the new members were significantly more cytotoxic than 1 on cell lines derived from human ATC. Structures inclusive of the 2′R,3R,4S,7R,8S,19R absolute configuration were assigned to 2–7 on the basis of detailed spectroscopic analysis, synthesis of different isomers, and application of ECD and Mosher’s methods. This work led to the identification of mycalol-578 (3) as the most potent analogue, with an IC50 of 2.3 μM on FRO cells.

Item Type:Article
Source:Copyright of this article belongs to American Chemical Society
ID Code:121927
Deposited On:23 Jul 2021 08:20
Last Modified:23 Jul 2021 08:20

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