Scaffold‐Hopping Cascade Yields Potent Inhibitors of 5‐Lipoxygenase

Franke, Lutz; Proschak, Ewgenij; Tanrıkulu, Yusuf; Schneider, Petra; Steinhilber, Dieter; Schneider, Gisbert

doi:10.1002/cmdc.200800153

Cited by 34 publications

(32 citation statements)

References 33 publications

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“…27). 140 Several of the high ranking hits are MCR reaction products, including G-3CR ( 173 ) and GBB-3CR ( 172 ). Clearly, such an approach is suited to economically screen large MCR libraries and to produce different hits based on different MCR scaffolds sic “scaffold-hopping”.…”

Section: Mcrs By Target Classmentioning

confidence: 99%

Chemistry and Biology Of Multicomponent Reactions

2012

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Section: Mcrs By Target Classmentioning

confidence: 99%

Chemistry and Biology Of Multicomponent Reactions

2012

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“…Here, the last step before biological testing of a compound is mostly done by visual inspection (includes ligand binding and conformation in the active site or the shape of the pharmacophore) and compound selection (Kumar and Zhang 2015). Another way is subjecting virtual hits to experimental validation, after which the information acquired from in vitro screening will be used to optimize the in silico model (Hofmann et al 2008;Zander et al 2010). Theoretically, this will produce more potent hits against the chosen target.…”

Section: Integration Of Drug Discovery Toolsmentioning

confidence: 99%

Role of computer-aided drug design in modern drug discovery

Macalino¹,

Gosu²,

Hong³

et al. 2015

Arch. Pharm. Res.

573

316

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Drug discovery utilizes chemical biology and computational drug design approaches for the efficient identification and optimization of lead compounds. Chemical biology is mostly involved in the elucidation of the biological function of a target and the mechanism of action of a chemical modulator. On the other hand, computer-aided drug design makes use of the structural knowledge of either the target (structure-based) or known ligands with bioactivity (ligand-based) to facilitate the determination of promising candidate drugs. Various virtual screening techniques are now being used by both pharmaceutical companies and academic research groups to reduce the cost and time required for the discovery of a potent drug. Despite the rapid advances in these methods, continuous improvements are critical for future drug discovery tools. Advantages presented by structure-based and ligand-based drug design suggest that their complementary use, as well as their integration with experimental routines, has a powerful impact on rational drug design. In this article, we give an overview of the current computational drug design and their application in integrated rational drug development to aid in the progress of drug discovery research.

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“…(2008) have applied Scaffold-Hopping to yield potent inhibitors of 5-LOX. Ligand-based virtual screening methods were used in an iterative fashion to identify new inhibitors [148]. The study consisted of four subsequent cycles of virtual screening, including 3D- and 2D-based methods and substructure searching.…”

Section: Application Of Lbdd In 5-lox Inhibitor Developmentmentioning

confidence: 99%

Structure and Ligand Based Drug Design Strategies in the Development of Novel 5- LOX Inhibitors

Aparoy¹,

Reddy²,

Reddanna

2012

CMC

142

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Lipoxygenases (LOXs) are non-heme iron containing dioxygenases involved in the oxygenation of polyunsaturated fatty acids (PUFAs) such as arachidonic acid (AA). Depending on the position of insertion of oxygen, LOXs are classified into 5-, 8-, 9-, 12- and 15-LOX. Among these, 5-LOX is the most predominant isoform associated with the formation of 5-hydroperoxyeicosatetraenoic acid (5-HpETE), the precursor of non-peptido (LTB4) and peptido (LTC4, LTD4, and LTE4) leukotrienes. LTs are involved in inflammatory and allergic diseases like asthma, ulcerative colitis, rhinitis and also in cancer. Consequently 5-LOX has become target for the development of therapeutic molecules for treatment of various inflammatory disorders. Zileuton is one such inhibitor of 5-LOX approved for the treatment of asthma.In the recent times, computer aided drug design (CADD) strategies have been applied successfully in drug development processes. A comprehensive review on structure based drug design strategies in the development of novel 5-LOX inhibitors is presented in this article. Since the crystal structure of 5-LOX has been recently solved, efforts to develop 5-LOX inhibitors have mostly relied on ligand based rational approaches. The present review provides a comprehensive survey on these strategies in the development of 5-LOX inhibitors.

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Scaffold‐Hopping Cascade Yields Potent Inhibitors of 5‐Lipoxygenase

Cited by 34 publications

References 33 publications

Chemistry and Biology Of Multicomponent Reactions

Chemistry and Biology Of Multicomponent Reactions

Role of computer-aided drug design in modern drug discovery

Structure and Ligand Based Drug Design Strategies in the Development of Novel 5- LOX Inhibitors

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