Synthesis and evaluation of diverse thio avarol derivatives as potential UVB photoprotective candidates

Amigo, María Luz; Terencio, María Carmen; Payá, Miguel; Iodice, Carmine; Rosa, Salvatore De

doi:10.1016/j.bmcl.2007.02.007

Cited by 13 publications

(16 citation statements)

References 31 publications

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“…In addition to the above-mentioned pharmacological properties, two monophenyl thioavarol derivatives have recently been described as lacking cytotoxicity, which could point to promising UVB photoprotective agents through the potent inhibition of NF-kappaB activation [151] with a mild antioxidant pharmacological profile. Various formulations with high avarol 1 content have been used for the prevention and treatment of psoriasis, dermatitis, skin cancer, tumors in the gastrointestinal tract, urinary tract and viral infection [152].…”

Section: Introductionmentioning

confidence: 99%

Synthetic Strategies to Terpene Quinones/Hydroquinones

Gordaliza

2012

Marine Drugs

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The cytotoxic and antiproliferative properties of many natural sesquiterpene-quinones and -hydroquinones from sponges offer promising opportunities for the development of new drugs. A review dealing with different strategies for obtaining bioactive terpenyl quinones/hydroquinones is presented. The different synthetic approches for the preparation of the most relevant quinones/hydroquinones are described.

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Section: Introductionmentioning

confidence: 99%

Synthetic Strategies to Terpene Quinones/Hydroquinones

Gordaliza

2012

Marine Drugs

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“…Two monophenyl thio-avarol derivatives which did not exhibit any cytotoxicity were considered to be promising UVB photoprotective agents due to their potent inhibition of NF-ĸβ activation and mild antioxidant pharmacological profile. 27 Pejin et al generated 11 additional thio-avarone analogues and tested these along with 12 of the derivatives constructed by Amigo et al in anti-microbial, brine shrimp lethality, free-radical scavenging, and acetylcholinesterase inhibition assays. The activity of the analogues varied in each test, allowing for SAR delineation.…”

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confidence: 99%

The use of isolated natural products as scaffolds for the generation of chemically diverse screening libraries for drug discovery

2016

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A diverse range of strategies leading to natural product derived or inspired screening libraries aims to increase the number of new chemical entities emerging per year. However, the use of isolated natural products as scaffolds for the semi-synthesis of larger biological screening libraries remains rare. This particular method avoids the time-consuming and resource intensive de novo synthetic strategy for scaffold production, and has become more feasible through improvements to synthetic and isolation methodologies. This Highlight examines the increasing popularity of small- to large-sized screening libraries generated directly from isolated natural products. Several of the examples detailed herein show how this strategy can lead to improvements in not only potency but also other important (and often forgotten) drug discovery parameters such as toxicity, selectivity, lipophilicity and bioavailability. However, there are still improvements to be made to this method, particularly in the choice of the natural product scaffold and the derivatising reagents used. Avoidance of known nuisance compounds or structural alert motifs (e.g. PAINS) that interfere with bioactivity screens, and impact downstream drug development will play a significant role in the future success of this methodology. Incorporation of rational design strategies that take into account the physicochemical parameters (e.g. log P, MW, HBA, HBD) of the final semi-synthetic library analogues will also facilitate the discovery and development of leads and drugs. A multi-pronged approach to drug discovery that incorporates the use of isolated natural product scaffolds for library generation will surely be beneficial.

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“…The most active compound was 4′-(methylamino)avarone 27, with an IC 50 value of 2.4 µM against melanoma Fem-X cells, and no cytotoxicity against normal lymphocytes. An in vitro cytotoxicity assay against U937 human histiocytic lymphoma cells determined the order of cytotoxic potency ((−)-neoavarone > (+)-avarone > (+)-aureol > (+)-avarol > (−)-neoavarol) and some aspects of their structure-activity relationships [20][21][22].…”

Section: Terpene-quinonesmentioning

confidence: 99%