Design, synthesis and evaluation of caffeic acid phenethyl ester-based inhibitors targeting a selectivity pocket in the active site of human aldo–keto reductase 1B10

Soda, Midori; Hu, Dawei; Endo, Shunsuke; Takemura, Mayuko; Li, Jie; Wada, Ryogo; Ifuku, Syohei; Zhao, Hai Tao; El‐Kabbani, Ossama; Ohta, Shozo; Yamamura, Ken‐ichi; Toyooka, Naoki; Hara, Akira; Matsunaga, Toshiyuki

doi:10.1016/j.ejmech.2011.12.034

Cited by 53 publications

(52 citation statements)

References 44 publications

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“…Caffeic acid silylation with TBSCl afforded silyl-protected caffeic acid 10 upon microwave irradiation [38]. This compound was esterified with ɷ-bromoalkylalcohols in the presence of EDC and DMAP to provide protected esters 11-17 in 41-60% yields [33]. Deprotection with TBAF and benzoic acid gave rise to esters 18-24 in 50-92% yields [34].…”

Section: Chemistrymentioning

confidence: 99%

Triclosan-caffeic acid hybrids: Synthesis, leishmanicidal, trypanocidal and cytotoxic activities

Otero

García

Palacios

et al. 2017

European Journal of Medicinal Chemistry

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The synthesis, cytotoxicity, anti-leishmanial and anti-trypanosomal activities of twelve triclosan-caffeic acid hybrids are described herein. The structure of the synthesized products was elucidated by a combination of spectrometric analyses. The synthesized compounds were evaluated against amastigotes forms of L. (V) panamensis, which is the most prevalent Leishmania species in Colombia, and against Trypanosoma cruzi, which is the pathogenic species to humans. Cytotoxicity was evaluated against human U-937 macrophages. Eight compounds were active against L. 26 and 28, the remaining compounds were toxic for mammalian cells, yet they have potential to be considered as candidates for anti-trypanosomal and anti-leishmanial drug development. The activity is dependent on the length of the alkyl linker with compound 19, bearing a four-carbon alkyl chain, the most performing hybrid. In general, hydroxyl groups increase both activity and cytotoxicity and the presence of the double bond in the side chain is not decisive for cytotoxicity and anti-protozoal activity.

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Section: Chemistrymentioning

confidence: 99%

Triclosan-caffeic acid hybrids: Synthesis, leishmanicidal, trypanocidal and cytotoxic activities

Otero

García

Palacios

et al. 2017

European Journal of Medicinal Chemistry

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“…A total of 64 AKR1B10 inhibitors with a range of different inhibitory activities were obtained from reported publica tions [1,[13][14][15] . The compounds were divided into the training set and the test set.…”

Section: Selection Of Compounds and Dataset Preparationmentioning

confidence: 99%

“…AKR1B10 inhibitors offer a promising choice for treatment of many types of human cancers. Several synthetic and natural compounds have been reported to inhibit AKR1B10 [1,[14][15][16] . AKR1B10 inhibitors may carry out the inhibition of the structurally similar human aldose reductase AKR1B1 in the AKR superfamily [1] .…”

Section: Introductionmentioning

confidence: 99%

Novel chemical scaffolds of the tumor marker AKR1B10 inhibitors discovered by 3D QSAR pharmacophore modeling

et al. 2015

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Aim: Recent evidence suggests that aldo-keto reductase family 1 B10 (AKR1B10) may be a potential diagnostic or prognostic marker of human tumors, and that AKR1B10 inhibitors offer a promising choice for treatment of many types of human cancers. The aim of this study was to identify novel chemical scaffolds of AKR1B10 inhibitors using in silico approaches. Methods: The 3D QSAR pharmacophore models were generated using HypoGen. A validated pharmacophore model was selected for virtual screening of 4 chemical databases. The best mapped compounds were assessed for their drug-like properties. The binding orientations of the resulting compounds were predicted by molecular docking. Density functional theory calculations were carried out using B3LYP. The stability of the protein-ligand complexes and the final binding modes of the hit compounds were analyzed using 10 ns molecular dynamics (MD) simulations. Results: The best pharmacophore model (Hypo 1) showed the highest correlation coefficient (0.979), lowest total cost (102.89) and least RMSD value (0.59). Hypo 1 consisted of one hydrogen-bond acceptor, one hydrogen-bond donor, one ring aromatic and one hydrophobic feature. This model was validated by Fischer's randomization and 40 test set compounds. Virtual screening of chemical databases and the docking studies resulted in 30 representative compounds. Frontier orbital analysis confirmed that only 3 compounds had sufficiently low energy band gaps. MD simulations revealed the binding modes of the 3 hit compounds: all of them showed a large number of hydrogen bonds and hydrophobic interactions with the active site and specificity pocket residues of AKR1B10. Conclusion: Three compounds with new structural scaffolds have been identified, which have stronger binding affinities for AKR1B10 than known inhibitors.

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“…Soda et al [74] compared the inhibitory actions of cinnamic acid derivatives extracted from propolis on AKR1B1 and recombinant AKR1B10, and found that caffeic acid phenethyl ester (CAPE,22) and its derivative 3-(4-hydroxy-2-methoxyphenyl) acrylic acid 3-(3-hydroxyphenyl) propyl ester (23) were the most potent competitive inhibitors for AKR1B10. Compound 23 displayed an AKR1B10/AKR1B1 selectivity ratio of 790; its high inhibitory selectivity was determined by the interactions between the residues Val-301 and Gln-114 of AKR1B10 and the 2-methoxy and 3-hydroxyl groups of itself, respectively.…”

Section: Natural-based Derivativesmentioning

confidence: 99%

“…The development of highly selective AKR1B10 inhibitors will likely bring great benefits to cancer patients. Thus far, several selective AKR1B10 inhibitors have been developed, such as, BDMC (18) [24] Oleanolic acid (20) [29], 3-(4-hydroxy-2-methoxyphenyl)acrylic acid 3-(3-hydroxyphenyl) propyl ester (23) [74], isolithocholic acid (8) [38], and androst -4-ene-3,6-dione (9) [30]. They seem to be the most selective inhibitors for AKR1B10.…”

Section: Current and Future Developmentsmentioning

confidence: 99%

Aldo-Keto Reductase Family 1 Member B10 Inhibitors: Potential Drugs for Cancer Treatment

Li¹,

He²,

Luo³

et al. 2016

PRA

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Cytosolic NADPH-dependent reductase AKR1B10 is a member of the aldo-keto reductase (AKR) superfamily. This enzyme is normally expressed in the gastrointestinal tract. However, it is overexpressed in many solid tumors, such as hepatocarcinoma, lung cancer and breast cancer. AKR1B10 may play a role in the formation and development of carcinomas through multiple mechanisms including detoxification of cytotoxic carbonyls, modulation of retinoic acid level, and regulation of cellular fatty acid synthesis and lipid metabolism. Studies have suggested that AKR1B10 may be a useful biomarker for cancer diagnosis and a potential target for cancer treatment. Over the last decade, a number of AKR1B10 inhibitors including aldose reductase inhibitors (ARIs), endogenous substances, natural-based derivatives and synthetic compounds have been developed, which could be novel anticancer drugs. This review provides an overview on related articles and patents about AKR1B10 inhibitors, with a focus on their inhibition selectivity and mechanism of function.

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Design, synthesis and evaluation of caffeic acid phenethyl ester-based inhibitors targeting a selectivity pocket in the active site of human aldo–keto reductase 1B10

Cited by 53 publications

References 44 publications

Triclosan-caffeic acid hybrids: Synthesis, leishmanicidal, trypanocidal and cytotoxic activities

Triclosan-caffeic acid hybrids: Synthesis, leishmanicidal, trypanocidal and cytotoxic activities

Novel chemical scaffolds of the tumor marker AKR1B10 inhibitors discovered by 3D QSAR pharmacophore modeling

Aldo-Keto Reductase Family 1 Member B10 Inhibitors: Potential Drugs for Cancer Treatment

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