Article
Biochemistry & Molecular Biology
Alena E. Kopytova, George N. Rychkov, Alexander A. Cheblokov, Elena V. Grigor'eva, Mikhail A. Nikolaev, Elena S. Yarkova, Diana A. Sorogina, Farid M. Ibatullin, Galina V. Baydakova, Artem D. Izyumchenko, Daria A. Bogdanova, Vitali M. Boitsov, Akim V. Rybakov, Irina V. Miliukhina, Vadim A. Bezrukikh, Galina N. Salogub, Ekaterina Y. Zakharova, Sofya N. Pchelina, Anton K. Emelyanov
Summary: Mutations in the GBA1 gene cause Gaucher disease and Parkinson's disease, and the pharmacological chaperone NCGC607 shows promise as a treatment. Molecular docking and simulations identified six allosteric binding sites on GCase, with two sites being preferential for NCGC607. Experimental results showed that NCGC607 increased GCase activity and protein levels, and decreased glycolipids concentration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Andres G. Santana, Kyle Robinson, Chelsea Vickers, Matthew C. Deen, Hong-Ming Chen, Stephen Zhou, Ben Dai, Maria Fuller, Alisdair B. Boraston, David J. Vocadlo, Lorne A. Clarke, Stephen G. Withers
Summary: In this study, we synthesized a novel pharmacological chaperone that improves the low enzyme activity in Gaucher disease patients. Cell and animal experiments demonstrated the effectiveness of this chaperone in enhancing enzymatic activity, suggesting its potential therapeutic value.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
My Lan Tran, Marc Borie-Guichot, Virginie Garcia, Abdelouahd Oukhrib, Yves Genisson, Thierry Levade, Stephanie Ballereau, Cedric-Olivier Turrin, Cecile Dehoux
Summary: The researchers synthesized phosphorus dendrimers with a cyclotriphosphazene core and decorated with monofluorocyclooctyne units. They grafted N-hexyl deoxynojirimycin inhibitors onto the surface of dendrimers. These synthesized iminosugars were tested as multivalent inhibitors of enzymes associated with Gaucher and Pompe lysosomal storage diseases, showing higher potency than the reference inhibitor. These dendrimers were also evaluated as pharmacological chaperones against Gaucher disease, exhibiting increased enzyme activity in Gaucher cells.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Fuying Li, Theresa A. Kopajtic, Jonathan L. Katz, Dan Luo, Thomas E. Prisinzano, Gregory H. Imler, Jeffrey R. Deschamps, Arthur E. Jacobson, Kenner C. Rice
Summary: This study focuses on the design and synthesis of enantiopure stereoisomers of N-2-phenylcyclopropylmethyl-substituted ortho-c oxide-bridged phenylmorphans as potential opioid receptor ligands. The compounds were synthesized and evaluated for their affinity and functional activity.
Article
Chemistry, Organic
Philippe N. Bolduc, Magnus Pfaffenbach, Vanna D. Blasczak, Steven R. Mathieu, Emily A. Peterson
Summary: This article presents an efficient synthesis method for a variety of N-substituted 2-pyridones, using ethyl nitroacetate and readily available primary amine building blocks, which can be widely used in large-scale and parallel medicinal chemistry.
Article
Biochemistry & Molecular Biology
Veronica Antipova, Lisa-Marie Steinhoff, Carsten Holzmann, Arndt Rolfs, Carlos Junior Hempel, Martin Witt, Andreas Wree
Summary: This study analyzed the alterations of organ weights in Npc1 mice under different treatment strategies. The results showed that Npc1(-/-) mice had smaller weights in the heart, liver, kidneys, testes, and glands, while female Npc1(-/-) mice had significantly smaller ovaries and uteri.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Jairo Villalona, Peyton M. Higgins, Andrew R. Buller
Summary: Non-canonical amino acids (ncAAs) serve as useful materials for developing new medicines, materials, and bioactive probes. In this study, the beta-subunit of tryptophan synthase, TrpB, was engineered through directed evolution to improve its activity with diverse amine nucleophiles. Mechanistic analysis revealed hindrance to high yields due to product re-entry and subsequent decomposition. Additional equivalents of l-serine were able to inhibit product re-entry through kinetic competition, facilitating preparative scale synthesis. Several beta-substituted amino acids were synthesized using a variety of aryl amine nucleophiles, including demonstration on a gram scale. These amino acids represent an underexplored class of building blocks for chemical biology and medicinal chemistry.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Jairo Villalona, Peyton M. Higgins, Andrew R. Buller
Summary: In this study, directed evolution was used to engineer the beta-subunit of tryptophan synthase for improved activity in the synthesis of beta-substituted amino acids. Mechanistic analysis revealed that product re-entry into the catalytic cycle and subsequent decomposition hindered high yields, but additional equivalents of l-serine could inhibit product re-entry and facilitate preparative scale synthesis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Chemistry, Multidisciplinary
Lemia Amarouche, Mohammed Amine Mehdid, Fawzia Taieb Brahimi, Fatima Belkhadem, Mohamed Karmaoui, Adil A. Othman
Summary: This study synthesized six N-benzyl-2-(5-substituted 1,3,4-oxadiazolyl) pyrrolidine derivatives and characterized their structures. The compounds with specific functional groups exhibited strong antioxidant and antibacterial activities.
JOURNAL OF SAUDI CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Gabriela Ramos-Duran, Aracely del Carmen Gonzalez-Zarate, Francisco Javier Enriquez-Medrano, Myrna Salinas-Hernandez, Marco A. De Jesus-Tellez, Ramon Diaz de Leon, Hector Ricardo Lopez-Gonzalez
Summary: A series of copolymers based on epsilon-caprolactone were synthesized to evaluate the effects of branching on crystallinity and thermal properties. The results showed that different copolymers with varying branching content exhibited different crystalline behaviors.
Article
Biochemistry & Molecular Biology
Francesca Clemente, Macarena Martinez-Bailen, Camilla Matassini, Amelia Morrone, Silvia Falliano, Anna Caciotti, Paolo Paoli, Andrea Goti, Francesca Cardona
Summary: This study reports the synthesis of five new trihydroxypiperidine iminosugars and identifies compound 12 as a potential therapeutic agent with chaperoning properties for GM1 gangliosidosis patients.
Article
Chemistry, Medicinal
Jan Pokorny, Denisa Olejnikova, Ivo Frydrych, Barbora Liskova, Sona Gurska, Sandra Benicka, Jan Sarek, Jana Kotulova, Marian Hajduch, Petr Dzubak, Milan Urban
Summary: New substituted dienes synthesized from betulinic acid showed higher cytotoxicity than betulinic acid itself, with compounds 4.22 and 4.39 demonstrating the most promising anti-cancer properties. These compounds induced apoptosis in cancer cells and disrupted the cell cycle, ultimately leading to cell death. Compound 4.22 was identified as the most effective candidate for the development of an anticancer drug based on its superior pharmacological parameters.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biology
Domenica N. Garzon, Yair Castillo, M. Gabriela Navas-Zuloaga, Leah Darwin, Abigail Hardin, Nora Culik, Anji Yang, Carlos Castillo-Garsow, Karen Rios-Soto, Leon Arriola, Aditi Ghosh
Summary: This article explores the effects of using pharmacological chaperones and interferons in combination to treat prions, and analyzes their impact on the growth rate of prions through a mathematical model.
JOURNAL OF THEORETICAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Penchala Narasimharao Meka, Eva Amatya, Sukhmanjit Kaur, Monimoy Banerjee, Ang Zuo, Rick T. Dobrowsky, Brian S. J. Blagg
Summary: This study investigated the efficacy of 3'- and 4'-substituted cyclohexyl scaffolds as noviomimetics in increasing mitochondrial bioenergetics, as a marker for cytoprotective potential, based on structure-activity relationship studies.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Xiaojing Chen, Guangbao Wang, Ali Mohammed Mohammed Alsayed, Zongxuan Du, Lu Liu, Yue Ma, Peng Liu, Qianwen Zhang, Xianxin Chen, Wenbin Chen, Faqing Ye, Xiaohui Zheng, Zhiguo Liu
Summary: A novel series of novel N-substituted (indole or indazole) benzamides were synthesized and evaluated for their antitumor properties. Compound 5d was found to inhibit the adhesion, migration, and invasion of osteosarcoma cells in vitro by regulating the expression of genes related to these processes, suggesting its potential as a chemotherapeutic drug for aggressive and/or metastatic cancers.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Organic
Faiza Diaba, Gisela Trenchs
Summary: The first violet light-mediated synthesis of gamma- and delta-lactams from N-alkenyl trichloroacetamides is reported in this paper. The reactions are conducted in tetrahydrofuran or 2-methyltetrahydrofuran as the sole solvent without catalysts or additives, under non-anhydrous conditions in an air atmosphere where the solvent serves as the radical initiator.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Feroze Hussain, Sajjad Ahmed, Ashiq Hussain Padder, Qazi Naveed Ahmed
Summary: This study reports a novel and efficient one-pot synthesis method for mixed phosphorotrithioates, which does not require supplementary additives and shows broad applicability.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Hyunjin Oh, Ikyon Kim
Summary: A new 1,2,4-triazole-pyrrolo[1,2-a]pyrazine hybrid system, 6-acylpyrrolo[1,2-a][1,2,4]triazolo[5,1-c]pyrazine, was synthesized using a catalyst-free method. This method involved sequential exposure of pyrrole-2-carbonitrile-derived substrates to DMF-DMA and acyl hydrazide, resulting in the formation of acylated pyrazine and 1,2,4-triazole rings, enabling the installation of various substituents at specific positions on the core skeleton.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Ming Yan, Si-fan Wang, Yong-po Zhang, Jin-zhong Zhao, Zhuo Tang, Guang-xun Li
Summary: Here we developed an efficient photocatalytic approach for the convenient preparation of sulfinamides. The reaction allows for the gram-scale preparation of sulfinamides and the one-pot synthesis of various sulfonyl amides.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Farzaneh Bandehali-Naeini, Zahra Tanbakouchian, Noushin Farajinia-Lehi, Nicolas Mayer, Morteza Shiri, Martin Breugst
Summary: Two tandem catalytic systems were developed for the synthesis of novel 3,4-disubstituted maleimides using the same Ugi adducts. Different maleimide structures can be synthesized using either Pd or Cu catalysis.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Tanya Raghava, Anjan Chattopadhyay, Subhadeep Banerjee, Nivedita Sarkar
Summary: Amine substitution of two ortho fluorine atoms of tetrafluoroterephthalonitrile through SNAr chemistry is easily achievable. But further fluorine substitution is only possible under forcing conditions, yielding valuable fluorophores for bioimaging.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Review
Chemistry, Organic
Anju Chadha, Santosh Kumar Padhi, Selvaraj Stella, Sowmyalakshmi Venkataraman, Thangavelu Saravanan
Summary: Alcohol dehydrogenases are enzymes that use cofactors for oxidation or reduction reactions of alcohols or carbonyl compounds. They are utilized in green chemistry and have applications in the production of pharmaceuticals. Recombinant enzymes have solved the challenge of producing purified enzymes in large quantities. Engineered alcohol dehydrogenases have been used in asymmetric synthesis in industry. Various methods have been established for regenerating expensive cofactors to make the enzymatic process more efficient and economically viable.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)