Identification and synthesis of mycalol analogues with improved potency against anaplastic thyroid carcinonia cell lines
| Title | Identification and synthesis of mycalol analogues with improved potency against anaplastic thyroid carcinonia cell lines |
| Publication Type | Journal Article |
| Year of Publication | 2017 |
| Authors | Cutignano, A, Seetharamsingh, B, D'Angelo, D, Nuzzo, G, Khairnar, PV, Fusco, A, D. Reddy, S, Fontana, A |
| Journal | Journal of Natural Products |
| Volume | 80 |
| Issue | 4 |
| Pagination | 1125-1133 |
| Date Published | APR |
| Type of Article | Article |
| 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-cytotokic than 1 on cell lines,derivecl from human ATC. Structures inclusive of the 2'R,3R,4S,7R,8S,19R absolute configuration were asigned 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 mycal61-578 (3) as the most potent analogue, with an IC50 of 2.3 mu M on FRO cells: |
| DOI | 10.1021/acs.jnatprod.7b00043 |
| Type of Journal (Indian or Foreign) | Foreign |
| Impact Factor (IF) | 3.662 |
Divison category:
Organic Chemistry