Abstract
Himalaquinones A-G, seven new anthraquinone-derived metabolites, were obtained from the Himalayan-basedStreptomycessp. PU-MM59. The chemical structures of the new compounds were identified based on cumulative analyses of HRESIMS and NMR spectra. Himalaquinones A-F were determined to be unique anthraquinones that contained unusual C-4a 3-methylbut-3-enoic acid aromatic substitutions, while himalaquinone G was identified as a new 5,6-dihydrodiol-bearing angucyclinone. Comparative bioactivity assessment (antimicrobial, cancer cell line cytotoxicity, impact on 4E-BP1 phosphorylation, and effect on axolotl embryo tail regeneration) revealed cytotoxic landomycin and saquayamycin analogues to inhibit 4E-BP1p and inhibit regeneration. In contrast, himalaquinone G, while also cytotoxic and a regeneration inhibitor, did not affect 4E-BP1p status at the doses tested. As such, this work implicates a unique mechanism for himalaquinone G and possibly other 5,6-dihydrodiol-bearing angucyclinones.
| Original language | English |
|---|---|
| Pages (from-to) | 1930-1940 |
| Number of pages | 11 |
| Journal | Journal of Natural Products |
| Volume | 84 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 23 2021 |
Bibliographical note
Publisher Copyright:© 2021 American Chemical Society and American Society of Pharmacognosy
Funding
This work was supported by National Institutes of Health grants R24 OD21479 (S.R.V., J.S.T.), R01 CA203257 (Q.B.S., J.S.T.), R01 CA175105 (Q.B.S.), R01 GM115261 (J.S.T.), the Center of Biomedical Research Excellence (COBRE) in Pharmaceutical Research and Innovation (CPRI, NIH P20 GM130456), the University of Kentucky College of Pharmacy, the University of Kentucky Markey Cancer Center, and the National Center for Advancing Translational Sciences (UL1TR000117 and UL1TR001998). This work was also supported by a Higher Education Commission (HEC) Pakistan grant (HEC-NRPU Project 2121). We thank the College of Pharmacy NMR Center (University of Kentucky) for NMR support.
| Funders | Funder number |
|---|---|
| Center of Biomedical Research Excellence | |
| HEC-NRPU | 2121 |
| University of Kentucky | |
| National Institutes of Health (NIH) | R01 CA175105, R24 OD21479, P20 GM130456, R01 GM115261, R01 CA203257 |
| National Center for Advancing Translational Sciences (NCATS) | UL1TR001998, UL1TR000117 |
| University of Kentucky Markey Cancer Center | |
| Higher Education Commission, Pakistan |
ASJC Scopus subject areas
- Analytical Chemistry
- Molecular Medicine
- Pharmacology
- Pharmaceutical Science
- Drug Discovery
- Complementary and alternative medicine
- Organic Chemistry
