Chemical diversity rather than cultivar diversity predicts natural enemy control of herbivore pests

The development of low-affinity fragment hits into higher affinity leads is a major hurdle in fragment-based drug design. Here we demonstrate an approach for the Rapid Elaboration of Fragments into Leads (REFiL) applying an integrated workflow that provides a systematic approach to generate higher-affinity binders without the need for structural information. The workflow involves the selection of commercial analogues of fragment hits to generate preliminary structure-activity relationships. This is followed by parallel microscale chemistry using chemoinformatically designed reagent libraries to rapidly explore chemical diversity. Upon completion of a fragment screen against Bromodomain-3 extra terminal (BRD3-ET) domain we applied the REFiL workflow, which allowed us to develop a series of tetrahydrocarbazole ligands that bind to the peptide binding site of BRD3-ET. With REFiL we were able to rapidly improve binding affinity >30-fold. The REFiL workflow can be applied readily to a broad range of protein targets without the need of a structure, allowing the efficient evolution of low-affinity fragments into higher affinity leads and chemical probes.<br>

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Effect of Brassica chinensis intercropping with Glycine max or Colocasia esculenta on Spodoptera litura and natural enemy predatory diversity in protected vegetable fields

CHINESE JOURNAL OF ECO-AGRICULTURE ◽

10.3724/sp.j.1011.2012.00236 ◽

2012 ◽

Vol 20 (2) ◽

pp. 236-241

Author(s):

Nian-Feng WAN ◽

Jie-Xian JIANG ◽

Xiang-Yun JI

Keyword(s):

Glycine Max ◽

Natural Enemy ◽

Spodoptera Litura ◽

Colocasia Esculenta ◽

Brassica Chinensis

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Oxazole-Based Compounds As Anticancer Agents

Current Medicinal Chemistry ◽

10.2174/0929867326666181203130402 ◽

2020 ◽

Vol 26 (41) ◽

pp. 7337-7371 ◽

Cited By ~ 3

Author(s):

Maria A. Chiacchio ◽

Giuseppe Lanza ◽

Ugo Chiacchio ◽

Salvatore V. Giofrè ◽

Roberto Romeo ◽

...

Keyword(s):

Cancer Research ◽

Drug Discovery ◽

Anticancer Agents ◽

Heterocyclic Compounds ◽

Chemical Diversity ◽

Biologically Active ◽

New Drugs ◽

The Core ◽

Anti Cancer ◽

Biologically Active Derivatives

: Heterocyclic compounds represent a significant target for anti-cancer research and drug discovery, due to their structural and chemical diversity. Oxazoles, with oxygen and nitrogen atoms present in the core structure, enable various types of interactions with different enzymes and receptors, favoring the discovery of new drugs. Aim of this review is to describe the most recent reports on the use of oxazole-based compounds in anticancer research, with reference to the newly discovered iso/oxazole-based drugs, to their synthesis and to the evaluation of the most biologically active derivatives. The corresponding dehydrogenated derivatives, i.e. iso/oxazolines and iso/oxazolidines, are also reported.

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