Review
Biochemistry & Molecular Biology
Himangshu Sonowal, Kota V. Ramana
Summary: Aldose Reductase (AR) is an enzyme involved in the polyol pathway of glucose metabolism and has been associated with the development of secondary diabetic complications as well as inflammatory disorders and cancer. Research is currently focused on exploring the potential therapeutic use of AR inhibitors beyond diabetic complications.
CURRENT MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Francesc Xavier Ruiz, Xavier Pares, Jaume Farres
Summary: Human aldo-keto reductase 1B10 (AKR1B10) is overexpressed in many cancer types and has been identified as an interesting drug target. Differences in inhibitor binding between AKR1B10 and aldose reductase (AR) have been observed, highlighting specific features that a selective AKR1B10 inhibitor should possess.
Review
Endocrinology & Metabolism
Sravya Jannapureddy, Mira Sharma, Gautham Yepuri, Ann Marie Schmidt, Ravichandran Ramasamy
Summary: Diabetes is a major risk factor for cardiovascular disease, and specific disease-modifying therapies are needed for diabetic patients. Research focusing on inhibiting the aldose reductase (AR) pathway to protect the cardiovascular system and the genetic polymorphisms associated with diabetic complications is ongoing to better understand and treat the consequences of diabetic cardiovascular disease.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Review
Pharmacology & Pharmacy
Jaka Dernovsek, Tihomir Tomasic
Summary: The Hsp90 family, including TRAP-1, Grp94, Hsp90 alpha, and Hsp9013, has been extensively studied as a potential target for cancer, neurological disorders, and infectious diseases. Non-selective Hsp90 inhibitors have not been successful due to lack of efficacy and induction of heat shock response. Developing selective inhibitors for specific Hsp90 isoforms has become a new approach.
PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Chemistry, Multidisciplinary
Yanqi Lei, Xin Zhang, Xiaonan Zhang, Long Xu, Wenchao Liu, Huan Chen, Changjin Zhu, Bing Ma
Summary: In this study, benzothiazolone derivatives were designed as potent inhibitors against ALR2 for diabetic complications. Among them, compound 6 c showed the highest activity, while compounds 4 c and 6 b also exhibited strong ALR2 inhibition and good antioxidant properties. Compound 6 b, with a C6-hydroxymethoxystyryl sidechain, is suggested as a promising candidate for further structural optimization.
Article
Medicine, General & Internal
Nianting Tong, Liangyu Wang, Huimin Gong, Lin Pan, Fuxiang Yuan, Zhanyu Zhou
Summary: This study describes the clinical manifestations of supra-large range nonperfusion area (SLRNPA) in diabetic retinopathy (DR). The results show that SLRNPA patients are more likely to be male, younger, with earlier DR onset, a smoking history, other comorbidities, and a higher HbA1c level. SLRNPA in DR is associated with higher rates of neovascular glaucoma and diabetic keratopathy and is difficult to treat with poor prognosis.
INTERNATIONAL JOURNAL OF CLINICAL PRACTICE
(2022)
Article
Pharmacology & Pharmacy
Wen-long Zhao, Di Xu, Jun-song Wang
Summary: This study discovered that torachrysone-8-O-beta-D-glucoside (TG), a natural product from Polygonum multi �orum Thunb., can effectively inhibit aldose reductase (AR) and has potent effects in clearing toxic substances and reducing inflammation. TG up-regulated the expression levels of several antioxidant factors, thus detoxifying harmful substances. This study provides new insights into developing therapeutic strategies for AR-related pathologies.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Antonios Kousaxidis, Lucia Kovacikova, Ioannis Nicolaou, Milan Stefek, Athina Geronikaki
Summary: A series of benzothiazole-based thiazolidinones were evaluated as potential inhibitors of aldose reductase, with compound 5 showing the most promising inhibitory activity. Molecular docking simulations provided insight into the binding mode of these compounds at the active site of human aldose reductase, and good membrane permeation and drug-likeness properties were predicted for the novel inhibitors according to Lipinski's rule of five.
MEDICINAL CHEMISTRY RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Aqeel Imran, Muhammad Tariq Shehzad, Syed Jawad Ali Shah, Mark Laws, Taha al-Adhami, Khondaker Miraz Rahman, Imtiaz Ali Khan, Zahid Shafiq, Jamshed Iqbal
Summary: Diabetic complications are caused by overexpression of aldose reductase, leading to oxidative stress and formation of advanced glycation end products. Current aldose reductase inhibitors have failed due to toxicity and poor pharmacokinetic profiles. This study developed thiosemicarbazone derivatives as selective inhibitors of ALR2 with antioxidant and antiglycation potential. Among the synthesized compounds, 3c showed strong and selective inhibition of ALR2, as well as good antioxidant and antiglycative properties.
Article
Biochemistry & Molecular Biology
Dixa Gautam, Michelle G. Pedler, Devatha P. Nair, Jonathan Mark Petrash
Summary: Research indicates that inserting a drug-eluting device capable of inhibiting PCO development into the lens capsule post-cataract surgery can significantly prevent cellular changes associated with posterior capsular opacification.
Article
Biochemistry & Molecular Biology
Yuanlin Liu, Hui Mo, Kun Zhang, Meili Yin, Sheng Yuan, Yanbing Li, Yifang Li, Wenda Zhu, Yiping Fan, Yancong Zeng, Hiroshi Kurihara, Rongrong He, Heru Chen
Summary: A series of new compounds based on 5f have been designed and synthesized, among which compound 6d shows excellent antioxidation and aldose reductase inhibitory activity. Animal model experiments demonstrate the therapeutic effect of 6d on diabetic complications.
BIOORGANIC CHEMISTRY
(2022)
Article
Clinical Neurology
Anna N. Ligezka, Silvia Radenkovic, Mayank Saraswat, Kishore Garapati, Wasantha Ranatunga, Wirginia Krzysciak, Hitoshi Yanaihara, Graeme Preston, William Brucker, Renee M. McGovern, Joel M. Reid, David Cassiman, Karthik Muthusamy, Christin Johnsen, Saadet Mercimek-Andrews, Austin Larson, Christina Lam, Andrew C. Edmondson, Bart Ghesquiere, Peter Witters, Kimiyo Raymond, Devin Oglesbee, Akhilesh Pandey, Ethan O. Perlstein, Tamas Kozicz, Eva Morava
Summary: Epalrestat, an aldose reductase inhibitor, increases PMM enzyme activity and improves N-glycosylation levels in PMM2-CDG patients. Urinary sorbitol levels may serve as a novel biomarker for disease severity and treatment response in future clinical trials for PMM2-CDG.
ANNALS OF NEUROLOGY
(2021)
Article
Clinical Neurology
Beibei Liang, Jin Wang, Guanxuanzi Zhang, Rui Wang, Yun Cai
Summary: This study aimed to assess the safety, tolerability, and pharmacokinetics of SYHA1402 in healthy Chinese subjects. The results showed that SYHA1402 was well tolerated and safe when administered as a single dose in the range of 25-800 mg, and over 50% of the unchanged drug was excreted in urine.
NEUROLOGY AND THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Belgin Sever, Mehlika Dilek Altintop, Yeliz Demir, Nalan Yilmaz, Gulsen Akalin Ciftci, Sukru Beydemir, Ahmet Ozdemir
Summary: Aldose reductase (AR) serves as a multi-disease target for therapeutic agents for diabetic complications and non-diabetic diseases. Through microwave-assisted synthesis, twenty new compounds were efficiently generated, with compound 20 identified as the most promising AR inhibitor with competitive inhibition, safety profile, and potential for oral bioavailability in the management of diabetic complications and nondiabetic diseases.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Article
Biochemistry & Molecular Biology
Anna Sandner, Khang Ngo, Christoph P. Sager, Frithjof Scheer, Michael Daude, Wibke E. Diederich, Andreas Heine, Gerhard Klebe
Summary: The study demonstrates that the transient specificity pocket of aldose reductase has unique opening characteristics for specific ligands, and confirms that an electron-deficient aromatic group is an important prerequisite for occupying the pocket. Additionally, the binding position of the ligand in the pocket is not affected by a pH shift between 5 and 8.
Article
Biochemistry & Molecular Biology
Jindrich Fanfrlik, Francesc X. Ruiz, Aneta Kadlcikova, Jan Rezac, Alexandra Cousido-Siah, Andre Mitschler, Susanta Haldar, Martin Lepsik, Michal H. Kolar, Pavel Majer, Alberto D. Podjarny, Pavel Hobza
ACS CHEMICAL BIOLOGY
(2015)
Article
Biochemistry & Molecular Biology
Alexandra Cousido-Siah, Francesc X. Ruiz, Isidro Crespo, Sergio Porte, Andre Mitschler, Xavier Pares, Alberto Podjarny, Jaume Farres
CHEMICO-BIOLOGICAL INTERACTIONS
(2015)
Article
Chemistry, Medicinal
Francesc X. Ruiz, Alexandra Cousido-Siah, Sergio Porte, Marta Dominguez, Isidro Crespo, Chris Rechlin, Andre Mitschler, Angel R. de Lera, Maria Jesus Martin, Jesus Angel de la Fuente, Gerhard Klebe, Xavier Pares, Jaume Farres, Alberto Podjarny
Article
Biochemistry & Molecular Biology
Martin E. Noguera, Ernesto A. Roman, Juan B. Rigal, Alexandra Cousido-Siah, Andre Mitschler, Alberto Podjarny, Javier Santos
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
(2015)
Article
Multidisciplinary Sciences
Joan Gimenez-Dejoz, Michal H. Kolar, Francesc X. Ruiz, Isidro Crespo, Alexandra Cousido-Siah, Alberto Podjarny, Oleg A. Barski, Jindrich Fanfrlik, Xavier Pares, Jaume Farres, Sergio Porte
Article
Biochemistry & Molecular Biology
Emel Timucin, Alexandra Cousido-Siah, Andre Mitschler, Alberto Podjarny, Osman Ugur Sezerman
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2016)
Article
Biochemical Research Methods
Firas Fadel, Yuguang Zhao, Raul Cachau, Alexandra Cousido-Siah, Francesc X. Ruiz, Karl Harlos, Eduardo Howard, Andre Mitschler, Alberto Podjarny
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2015)
Article
Biochemistry & Molecular Biology
Wanda M. Valsecchi, Alexandra Cousido-Siah, Lucas A. Defelipe, Andre Mitschler, Alberto Podjarny, Javier Santos, Jose M. Delfino
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2016)
Article
Chemistry, Multidisciplinary
Mathieu L. Lepage, Jeremy P. Schneider, Anne Bodlenner, Alessandra Meli, Francesco De Riccardis, Marjorie Schmitt, Celine Tarnus, Nha-Thi Nguyen-Huynh, Yannis-Nicolas Francois, Emmanuelle Leize-Wagner, Catherine Birck, Alexandra Cousido-Siah, Alberto Podjarny, Irene Izzo, Philippe Compain
CHEMISTRY-A EUROPEAN JOURNAL
(2016)
Article
Multidisciplinary Sciences
Denise Martinez-Zapien, Francesc Xavier Ruiz, Juline Poirson, Andre Mitschler, Juan Ramirez, Anne Forster, Alexandra Cousido-Siah, Murielle Masson, Scott Vande Pol, Alberto Podjarny, Gilles Trave, Katia Zanier
Article
Chemistry, Multidisciplinary
E. I. Howard, B. Guillot, M. P. Blakeley, M. Haertlein, M. Moulin, A. Mitschler, A. Cousido-Siah, F. Fadel, W. M. Valsecchi, Takashi Tomizaki, T. Petrova, J. Claudot, A. Podjarny
Article
Biochemistry & Molecular Biology
Fabrice A. C. Klein, Gabrielle Zeder-Lutz, Alexandra Cousido-Siah, Andre Mitschler, Aline Katz, Pascal Eberling, Jean-Louis Mandel, Alberto Podjarny, Yvon Trottier
HUMAN MOLECULAR GENETICS
(2013)
Article
Multidisciplinary Sciences
Firas Fadel, Yuguang Zhao, Alexandra Cousido-Siah, Francesc X. Ruiz, Andre Mitschler, Alberto Podjarny
Article
Biochemical Research Methods
S. J. Fisher, M. P. Blakeley, E. I. Howard, I. Petit-Haertlein, M. Haertlein, A. Mitschler, A. Cousido-Siah, A. G. Salvay, A. Popov, C. Muller-Dieckmann, T. Petrova, A. Podjarny
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2014)
Article
Biochemical Research Methods
Alexandra Cousido-Siah, Francesc X. Ruiz, Andre Mitschler, Sergio Porte, Angel R. de Lera, Maria J. Martin, Sonia Manzanaro, Jesus A. de la Fuente, Felix Terwesten, Michael Betz, Gerhard Klebe, Jaume Farres, Xavier Pares, Alberto Podjarny
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2014)
Article
Biochemistry & Molecular Biology
Ankita Chadda, Alexander G. Kozlov, Binh Nguyen, Timothy M. Lohman, Eric A. Galburt
Summary: In this study, it was found that the DNA damage response in Mycobacterium tuberculosis differs from well-studied model bacteria. The DNA repair helicase UvrD1 in Mtb is activated through a redox-dependent process and is closely associated with the homo-dimeric Ku protein. Additionally, Ku protein is shown to stimulate the helicase activity of UvrD1.
JOURNAL OF MOLECULAR BIOLOGY
(2024)