Synthesis of gallic acid based naphthophenone fatty acid amides as cathepsin D inhibitors

Srivastava, Vandana; Saxena, Hari Om; Shanker, Karuna; Kumar, Jonnala Kotesh; Luqman, Suaib; Gupta, Madan M.; Khanuja, S. P. S.; Negi, Arvind S.

doi:10.1016/j.bmcl.2006.06.010

Cited by 23 publications

(8 citation statements)

References 32 publications

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“…Cathepsin D plays an important role during meat processing, which may finally influence meat tenderness and quality traits (Cafe et al, 2010;Godiksen et al, 2009). A number of myofibrillar proteins, such as titin and connectin, were found to be susceptible to hydrolysis by cathepsin D.It is essential for proteolysis of proteins to help in regulating cell growth and tissue homeostasis, which is expressed in most cells and over-expressed in breast cancer cells (Masson et al, 2011;Srivastava et al, 2006;Tandon et al, 1990), even involved in tumor metastasis (Ollinger, 2000;Lah et al, 1996;Rochefort et al, 1996). Nowadays, protease inhibitors have been traditionally developed from natural product screening for lead molecules with subsequent optimization (Chaturvedi et al, 2013), thus, chitosan-based cathepsin D inhibitor is a potential.…”

Section: Cathepsin D Inhibitionmentioning

confidence: 99%

Synthesis, antioxidant and cathepsin D inhibition activity of quaternary ammonium chitosan derivatives

Duan

Huang

et al. 2016

Carbohydrate Polymers

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Two (2-hydroxypropyl) trimethyl ammonium and/or imidazole-based quaternary ammonium chitosan derivatives (NHT-chitosan and Im-OHT-chitosan) were synthesized by using nucleophilic substitution reaction. These two synthesized chitosan derivatives were characterized by Fourier transform infrared spectroscopy, NMR spectra, and UV-visible spectra. The applications as antioxidant agents and cathepsin D inhibitors were further investigated. Both of quaternary ammonium chitosan derivatives exhibited good antioxidant activity upon scavenging against hydroxyl radical and hydrogen peroxide as well as the lipid peroxidation inhibition in the linoleic acid emulsion system. They also exhibited good inhibition activity of cathepsin D protease. NHT-chitosan and Im-OHT-chitosan are potential the natural, healthy and safe preservatives in food industry.

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Section: Cathepsin D Inhibitionmentioning

confidence: 99%

Synthesis, antioxidant and cathepsin D inhibition activity of quaternary ammonium chitosan derivatives

Duan

Huang

et al. 2016

Carbohydrate Polymers

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“…Compound 14 with β-naphthyl exhibited the lowest IC 50 of 0.6 nM. Inhibitors with a single aromatic ring (15,16,17, and 9) had slightly higher IC 50 values. The minimal difference between 9 with benzyl and 18 with cyclohexyl-methyl suggested that hydrophobic interaction prevails over aromatic stacking with the several aromatic residues in the S1 pocket.…”

Section: ■ Resultsmentioning

confidence: 97%

Biomimetic Macrocyclic Inhibitors of Human Cathepsin D: Structure–Activity Relationship and Binding Mode Analysis

et al. 2020

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Human cathepsin D (CatD), a pepsin-family aspartic protease, plays an important role in tumor progression and metastasis. Here, we report the development of biomimetic inhibitors of CatD as novel tools for regulation of this therapeutic target. We designed a macrocyclic scaffold to mimic the spatial conformation of the minimal pseudo-dipeptide binding motif of pepstatin A, a microbial oligopeptide inhibitor, in the CatD active site. A library of more than 30 macrocyclic peptidomimetic inhibitors was employed for scaffold optimization, mapping of subsite interactions, and profiling of inhibitor selectivity. Furthermore, we solved high-resolution crystal structures of three macrocyclic inhibitors with low nanomolar or subnanomolar potency in complex with CatD and determined their binding mode using quantum chemical calculations. The study provides a new structural template and functional profile that can be exploited for design of potential chemotherapeutics that specifically inhibit CatD and related aspartic proteases.

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“…Over the past 20 years, a large number of nonpeptidic and peptidic Cath D inhibitors have been reported . Some typical nonpeptidic Cath D inhibitors that discovered by computer‐aided drug design or random screening have been documented previously .…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, and bioactivities of tasiamide B derivatives as cathepsin D inhibitors

Bao

et al. 2019

Journal of Peptide Science

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Cathepsin D (Cath D) is overexpressed and hypersecreted by malignant tumors and involved in the progress of tumor invasion, proliferation, metastasis, and apoptosis.Cath D has been considered as a potential target to treat cancer. Our previous studies revealed that tasiamide B derivatives TB-9 and TB-11 exhibited high potent inhibition against Cath D and other aspartic proteases, but their molecular weights are still high, and the role of each residue is unknown yet. Based on this, two series of tasiamide B derivatives have been designed, synthesized, and evaluated for their inhibitory activity against Cath D/Cath E/BACE1. Enzymatic assays revealed that the target compound 1 with lower molecule weight showed good inhibitory activity against Cath D with IC 50 of 3.29 nM and satisfactory selectivity over Cath E (72-fold) and BACE1 (295-fold), which could be a valuable template for the design of highly potent and selective Cath D inhibitors.

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Synthesis of gallic acid based naphthophenone fatty acid amides as cathepsin D inhibitors

Cited by 23 publications

References 32 publications

Synthesis, antioxidant and cathepsin D inhibition activity of quaternary ammonium chitosan derivatives

Synthesis, antioxidant and cathepsin D inhibition activity of quaternary ammonium chitosan derivatives

Biomimetic Macrocyclic Inhibitors of Human Cathepsin D: Structure–Activity Relationship and Binding Mode Analysis

Design, synthesis, and bioactivities of tasiamide B derivatives as cathepsin D inhibitors

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