Next Article in Journal
Determination of the Bridging Ligand in the Active Site of Tyrosinase
Previous Article in Journal
Stenotrophomonas maltophilia: A Gram-Negative Bacterium Useful for Transformations of Flavanone and Chalcone
Previous Article in Special Issue
Phaseolus acutifolius Lectin Fractions Exhibit Apoptotic Effects on Colon Cancer: Preclinical Studies Using Dimethilhydrazine or Azoxi-Methane as Cancer Induction Agents
Article Menu

Export Article

Open AccessArticle
Molecules 2017, 22(11), 1834; doi:10.3390/molecules22111834

‘Click Chemistry’ Synthesis of Novel Natural Product-Like Caged Xanthones Bearing a 1,2,3-Triazole Moiety with Improved Druglike Properties as Orally Active Antitumor Agents

1,2
,
1,3
,
1,3
,
1,3,* and 1,4,*
1
Jiangsu Key Laboratory of Drug Design and Optimization, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
2
Department of Pharmaceutical Engineering, China Pharmaceutical University, Nanjing 211198, China
3
Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21009, China
4
Department of Organic Chemistry, China Pharmaceutical University, Nanjing 211198, China
*
Authors to whom correspondence should be addressed.
Received: 12 October 2017 / Revised: 26 October 2017 / Accepted: 26 October 2017 / Published: 27 October 2017
(This article belongs to the Special Issue Natural Products: Anticancer Potential and Beyond)
View Full-Text   |   Download PDF [1997 KB, uploaded 27 October 2017]   |  

Abstract

DDO-6101, a natural-product-like caged xanthone discovered previously in our laboratory based on the pharmacophoric scaffold of the Garcinia natural product gambogic acid (GA), shows potent cytotoxicity in vitro, but poor efficacy in vivo due to its poor druglike properties. In order to improve the druglike properties and in vivo antitumor potency, a novel series of ten triazole-bearing caged xanthone derivatives of DDO-6101 has been efficiently synthesized by ‘click chemistry’ and evaluated for their in vitro antitumor activity and druglike properties. Most of the target compounds have sustained cytotoxicity against A549, HepG2, HCT116, and U2OS cancer cells and possess improved aqueous solubility, as well as permeability. Notably, these caged xanthones are also active towards taxol-resistant or cisplatin-resistant A549 cancer cells. Taking both the in vitro activities and druglike properties into consideration, compound 8g has been advanced into in vivo efficacy experiments. The results reveal that 8g (named as DDO-6318), both by intravenous or per os administration, are much more potent than the lead DDO-6101 in A549-transplanted mice models and it could be a promising antitumor candidate for further evaluation. View Full-Text
Keywords: caged xanthones; click chemistry; druglike; antitumor; natural-product-like caged xanthones; click chemistry; druglike; antitumor; natural-product-like
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Li, X.; Wu, Y.; Wang, Y.; You, Q.; Zhang, X. ‘Click Chemistry’ Synthesis of Novel Natural Product-Like Caged Xanthones Bearing a 1,2,3-Triazole Moiety with Improved Druglike Properties as Orally Active Antitumor Agents. Molecules 2017, 22, 1834.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top