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Issue 35, 2018
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Natural products as modulators of the cyclic-AMP pathway: evaluation and synthesis of lead compounds

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Abstract

It is now well recognized that the normal cellular response in mammalian cells is critically regulated by the cyclic-AMP (cAMP) pathway through the appropriate balance of adenylyl cyclase (AC) and phosphodiesterase-4 (PDE4) activities. Dysfunctions in the cAMP pathway have major implications in various diseases like CNS disorders, inflammation and cardiac syndromes and, hence, the modulation of cAMP signalling through appropriate intervention of AC/PDE4 activities has emerged as a promising new drug discovery strategy of current interest. In this context, synthetic small molecules have had limited success so far and therefore parallel efforts on natural product leads have been actively pursued. The early promise of using the diterpene forskolin and its semi-synthetic analogs as AC activators has given way to new leads in the last decade from novel natural products like the marine sesterterpenoids alotaketals and ansellones and the 9,9′-diarylfluorenone cored selaginpulvilins, etc. and their synthesis has drawn much attention. This review captures these contemporary developments, particularly total synthesis campaigns and structure-guided analog design in the context of AC and PDE-4 modulating attributes and the scope for future possibilities.

Graphical abstract: Natural products as modulators of the cyclic-AMP pathway: evaluation and synthesis of lead compounds

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Publication details

The article was received on 12 Jun 2018, accepted on 14 Aug 2018 and first published on 24 Aug 2018


Article type: Review Article
DOI: 10.1039/C8OB01388H
Citation: Org. Biomol. Chem., 2018,16, 6372-6390
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    Natural products as modulators of the cyclic-AMP pathway: evaluation and synthesis of lead compounds

    S. Sengupta and G. Mehta, Org. Biomol. Chem., 2018, 16, 6372
    DOI: 10.1039/C8OB01388H

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