Chemistry and Bioactivity of ent-Kaurene Diterpenoids

C. Ding, Y. Ding, H. Chen, Jia Zhou

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Citations (Scopus)

Abstract

The ent-kaurene diterpenoids, one unique category of the diterpenoid family, have a long-standing history of research and medical applications in traditional Eastern remedies and have garnered increasing interest since the last century due to their structural diversity and complexity, together with extensive bioactivity profiles. So far, more than 1300 members of the ent-kaurene diterpene family of natural products have been isolated from the genus Isodon, a famous traditional Chinese folk medicine with well-demonstrated medicinal attributes. In light of their fascinating chemical structures, most of the ent-kaurene diterpenoids known to date incorporate a perhydro-phenanthren fragment conjugated with a cyclopentane ring to build up the tetracyclic core scaffold. Biosynthetically, these ent-kauranoids are derived from geranylgeranyl pyrophosphate (GGPP) through initial cyclization of GGPP and subsequent modifications of the resulting bicyclic carbon skeleton. Thus, the dazzling structural features of the ent-kaurene diterpenoids, sometimes combined with their low natural abundance, have inspired researchers to make numerous endeavors from the biosynthesis and chemical synthesis perspectives over the past decades. The structural feature of the bridged bicyclo[3.2.1]octane ring system, for example, has been a synthetic hot topic among organic and medicinal chemists. More importantly, extensive biological studies have demonstrated that ent-kauranoids exhibit considerable pharmacological activities including antitumor, antibacterial, antiviral, and antiinflammatory effects. Of particular interest is the attractive anticancer pharmacological profile of this class of natural compounds, such as oridonin and eriocalyxin B. Accumulating mechanistic investigations have revealed that ent-kauranoids possess versatile anticancer activities by regulating a series of transcription factors, protein kinases, as well as pro- and/or anti-apoptotic proteins, including but not limited to telomerase inhibition, p53 activation, and NF-kB inhibition. Last but not least, the clinical development of ent-kauranoids is usually hampered, to a large degree, by their relatively moderate potency, limited aqueous solubility, and bioavailability. Accordingly, rational modification based on the scaffold of ent-kauranoids to improve the anticancer activity profile and drug-like properties presents a promising alternative strategy for the development of high-quality, natural product-like drug candidates existing outside the repertoire of compounds found in nature. In this chapter we provide a brief overview of recent advances in chemistry and biology of ent-kaurene diterpenoids from several perspectives of biosynthesis, total synthesis, and pharmacological activities as well as structural optimization.

Original languageEnglish (US)
Title of host publicationStudies in Natural Products Chemistry
PublisherElsevier B.V.
Pages141-197
Number of pages57
Volume54
DOIs
StatePublished - 2017

Publication series

NameStudies in Natural Products Chemistry
Volume54
ISSN (Print)1572-5995

Fingerprint

Kaurane Diterpenes
Diterpenes
Bioactivity
Apoptosis Regulatory Proteins
Biosynthesis
Pharmacology
Biological Products
Scaffolds
Isodon
Cyclopentanes
Structural optimization
NF-kappa B
Telomerase
Cyclization
Traditional Medicine
Medical applications
Skeleton
Pharmaceutical Preparations
Solubility
Protein Kinases

Keywords

  • Anticancer agents
  • Biological activity
  • Diterpenoids
  • Drug discovery
  • Natural products

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry

Cite this

Ding, C., Ding, Y., Chen, H., & Zhou, J. (2017). Chemistry and Bioactivity of ent-Kaurene Diterpenoids. In Studies in Natural Products Chemistry (Vol. 54, pp. 141-197). (Studies in Natural Products Chemistry; Vol. 54). Elsevier B.V.. https://doi.org/10.1016/B978-0-444-63929-5.00005-X

Chemistry and Bioactivity of ent-Kaurene Diterpenoids. / Ding, C.; Ding, Y.; Chen, H.; Zhou, Jia.

Studies in Natural Products Chemistry. Vol. 54 Elsevier B.V., 2017. p. 141-197 (Studies in Natural Products Chemistry; Vol. 54).

Research output: Chapter in Book/Report/Conference proceedingChapter

Ding, C, Ding, Y, Chen, H & Zhou, J 2017, Chemistry and Bioactivity of ent-Kaurene Diterpenoids. in Studies in Natural Products Chemistry. vol. 54, Studies in Natural Products Chemistry, vol. 54, Elsevier B.V., pp. 141-197. https://doi.org/10.1016/B978-0-444-63929-5.00005-X
Ding C, Ding Y, Chen H, Zhou J. Chemistry and Bioactivity of ent-Kaurene Diterpenoids. In Studies in Natural Products Chemistry. Vol. 54. Elsevier B.V. 2017. p. 141-197. (Studies in Natural Products Chemistry). https://doi.org/10.1016/B978-0-444-63929-5.00005-X
Ding, C. ; Ding, Y. ; Chen, H. ; Zhou, Jia. / Chemistry and Bioactivity of ent-Kaurene Diterpenoids. Studies in Natural Products Chemistry. Vol. 54 Elsevier B.V., 2017. pp. 141-197 (Studies in Natural Products Chemistry).
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