Total synthesis and biological evaluation of the natural product (−)-cyclonerodiol, a new inhibitor of IL-4 signaling

The lipoxazolidinone family of marine natural products, with an unusual 4-oxazolidinone heterocycle at their core, represents a new scaffold for antimicrobial discovery; however, questions regarding their mechanism of action and high lipophilicity have likely slowed follow-up studies. Herein, we report the first synthesis of lipoxazolidinone A, 15 structural analogs to explore its active pharmacophore, and initial resistance and mechanism of action studies. These results suggest that 4-oxazolidinones are valuable scaffolds for antimicrobial development and reveal simplified lead compounds for further optimization.

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Rational Design, Synthesis and Biological Evaluation of Novel Derivatives Based on in vivo Metabolism of Natural Product β-elemene

Letters in Drug Design & Discovery ◽

10.2174/1570180814666171108093021 ◽

2018 ◽

Vol 15 (8) ◽

pp. 905-912 ◽

Cited By ~ 1

Author(s):

Renren Bai ◽

Xiaokang Jie ◽

Eric Salgado ◽

Jian Sun ◽

Yao Zhu ◽

...

Keyword(s):

Natural Product ◽

Rational Design ◽

Biological Evaluation ◽

In Vivo Metabolism ◽

Design Synthesis ◽

Synthesis And Biological Evaluation

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Xylochemical Synthesis and Biological Evaluation of Shancigusin C and Bletistrin G

Molecules ◽

10.3390/molecules26113224 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3224

Author(s):

Leander Geske ◽

Ulrich Kauhl ◽

Mohamed E. M. Saeed ◽

Anja Schüffler ◽

Eckhard Thines ◽

...

Keyword(s):

Total Synthesis ◽

Biological Activities ◽

Biological Evaluation ◽

Aromatic Substitution ◽

Substitution Reactions ◽

Total Syntheses ◽

Wittig Olefination ◽

Starting Point ◽

Perkin Reaction ◽

Synthesis And Biological Evaluation

The biological activities of shancigusin C (1) and bletistrin G (2), natural products isolated from orchids, are reported along with their first total syntheses. The total synthesis of shancigusin C (1) was conducted by employing the Perkin reaction to forge the central stilbene core, whereas the synthesis of bletistrin G (2) was achieved by the Wittig olefination followed by several regioselective aromatic substitution reactions. Both syntheses were completed by applying only renewable starting materials according to the principles of xylochemistry. The cytotoxic properties of shancigusin C (1) and bletistrin G (2) against tumor cells suggest suitability as a starting point for further structural variation.

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Synthesis and Biological Evaluation of Hydroxylated Monocarbonyl Curcumin Derivatives as Potential Inducers of Neprilysin Activity

Biomedicines ◽

10.3390/biomedicines9080955 ◽

2021 ◽

Vol 9 (8) ◽

pp. 955

Author(s):

Dimitris Matiadis ◽

See-Ting Ng ◽

Eric H.-L. Chen ◽

Georgia Nigianni ◽

Veroniki P. Vidali ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Therapeutic Strategy ◽

Specific Inhibitor ◽

Biological Evaluation ◽

Lead Compound ◽

Cleavage Activity ◽

Curcumin Derivatives ◽

Aβ Clearance ◽

Activity Enhancement ◽

Synthesis And Biological Evaluation

Background: Alzheimer’s disease (AD) involves impairment of Aβ clearance. Neprilysin (NEP) is the most efficient Aβ peptidase. Enhancement of the activity or expression of NEP may provide a prominent therapeutic strategy against AD. Aims: Ten hydroxylated monocarbonyl curcumin derivatives were designed, synthesized and evaluated for their NEP upregulating potential using sensitive fluorescence-based Aβ digestion and inhibition assays. Results: Compound 4 was the most active one, resulting in a 50% increase in Aβ cleavage activity. Cyclohexanone-bearing derivatives exhibited higher activity enhancement compared to their acetone counterparts. Inhibition experiments with the NEP-specific inhibitor thiorphan resulted in dramatic cleavage reduction. Conclusion: The increased Aβ cleavage activity and the ease of synthesis of 4 renders it an extremely attractive lead compound.

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