Article
Biochemistry & Molecular Biology
Lorenzo Cianni, Fernanda Dos Reis Rocho, Vinicius Bonatto, Felipe Cardoso Prado Martins, Jeronimo Lameira, Andrei Leitao, Carlos A. Montanari, Anwar Shamim
Summary: In this study, a new set of peptide-like nitrile-based cathepsin inhibitors were synthesized using a knowledge-based design approach. Three compounds showed nanomolar inhibition of CatB with selectivity over other cysteine proteases. Through a structure-based design, selective CatB inhibition was achieved, and successful bioisosteric replacement of the amide bond for a sulfonamide one was demonstrated.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Yan-Mei Wei, Li Yang, Hao Wang, Cai-Hong Cai, Zhi-Bao Chen, Hui-Qin Chen, Wen-Li Mei, Hao-Fu Dai
Summary: Triterpenoids with dual inhibition against AChE and BuChE were discovered in Inonotus obliquus, showing potential as drug candidates for the treatment of Alzheimer's disease.
Article
Biochemistry & Molecular Biology
Ana Mitrovic, Janja Zavrsnik, Georgy Mikhaylov, Damijan Knez, Ursa Pecar Fonovic, Petra Matjan Stefin, Miha Butinar, Stanislav Gobec, Boris Turk, Janko Kos
Summary: The study highlights the potential of a triazole-based selective reversible inhibitor, Z9, in reducing tumor progression by targeting lysosomal cysteine cathepsin, particularly cathepsin X. The simultaneous inhibition of cathepsin X and cathepsin B shows a synergistic effect in impairing tumor cell migration and growth. This research reveals the innovative approach of using Z9 in combination with other peptidase inhibitors to overcome resistance to antipeptidase therapy.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jing Zhang, Qiu-Sha Pan, Xing-Kai Qian, Xiang-Lu Zhou, Ya-Jie Wang, Rong-Jing He, Le-Tian Wang, Yan-Ran Li, Hong Huo, Cheng-Gong Sun, Lei Sun, Li-Wei Zou, Ling Yang
Summary: In this study, two triterpenoid derivatives with strong inhibitory effects on both pancreatic lipase (PL) and human carboxylesterase 1A (hCES1A) were discovered, showing potential as promising lead compounds for drug development.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Plant Sciences
Chun-Yang Zhang, Zhao-Jun Chu, Jin-Chuan Zhou, Shu-Gong Liu, Jiao-Zhen Zhang, Lining Qian, Hong-Xiang Lou
Summary: Ten new triterpenoids were isolated and purified from the Chinese liverwort Lepidozia reptans, with compound 7 showing inhibitory effects on a panel of cancer cell lines and inducing PC-3 cell death through mitochondrial-related apoptosis.
JOURNAL OF NATURAL PRODUCTS
(2021)
Article
Chemistry, Organic
Wen-Chao Tu, Xing-Jie Zhang, Ying-Xin Zhao, Wei-Chi Chen, Xing-Yu Zhang, Chang-Lin Yang, Muhammad Aurang Zeb, Xiao-Li Li, Kaunda-Joseph Sakah, Rui-Han Zhang, Mei-Feng Liu, Wei-Lie Xiao
Summary: Compounds Wulfenioidins A-C (1-3), isolated from Orthosiphon wulfenioides, possess an unprecedented tricyclic skeleton with a 6/5-5 configuration and a unique spiro[4.4] nonane structure. Elucidation of their structures was achieved through X-ray diffraction, quantum chemical calculations, and extensive spectroscopic methods. Compound 3 exhibited potent inhibitory activity against the NLRP3 inflammasome and effectively blocked NLRP3 inflammasome-induced pyroptosis in J774A.1 cells by inhibiting caspase-1 activation, GSDMD-NT production, and IL-1 beta secretion.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Plant Sciences
Zhi Cheng, Wei Wu, Yu Liu, Shuo Chen, Hongji Li, Xingchi Yang, Xiaofan Zhu, Xuxiang Chen, Lan Yan, Zhiyong Chu, Peng Sun
Summary: Ibrexafungerp is a new class of antifungal drugs and the first one to be approved in the past 20 years. It is a semi-synthetic derivative of engulfungin, a natural triterpene glycoside that inhibits fungal biosynthesis. The study on Hormonema carpetanum led to the discovery of two new analogues of engulfungin, engulfungins B and C, which may have implications for the biosynthesis of engulfungin. The antifungal activity of engulfungins B and C is lower than that of engulfungin.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Plant Sciences
Zhi Cheng, Wei Wu, Yu Liu, Shuo Chen, Hongji Li, Xingchi Yang, Xiaofan Zhu, Xuxiang Chen, Lan Yan, Zhiyong Chu, Peng Sun
Summary: Ibrexafungerp, a new class of antifungal drugs, is an inhibitor of fungal beta-(1,3)-d-glucan synthase and has been approved in the last 20 years. It is a semisynthetic derivative of enfumafungin, a naturally occurring triterpene glycoside. Researchers discovered two new analogues, enfumafungins B and C, as well as enfumafungin, by investigating Hormonema carpetanum. The structures of enfumafungins were determined through NMR and MS spectroscopic data analysis. Enfumafungins B and C showed lower antifungal activity compared to enfumafungin, indicating the importance of the C-2 substituents and the C-19 carboxy acid for activity. Molecular docking simulations revealed significant hydrogen bond interactions between enfumafungins and beta-(1,3)-d-glucan synthase, which may aid in the development of new antifungal agents.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Chemistry, Medicinal
Sifan Lyu, Yunshuo Zhao, Xiao Zeng, Xiaotong Chen, Qingqing Meng, Zhe Ding, Wenshan Zhao, Yuanming Qi, Yanfeng Gao, Jiangfeng Du
Summary: This study identified novel compounds with CD73 inhibitory activity using computer-aided drug discovery and enzymatic-based assays. Compounds based on phelligridin showed the best inhibitory effects and may serve as lead compounds for developing CD73-targeting drugs. The molecular weight of the identified inhibitors is around 500 Daltons, and they are predicted to primarily form hydrogen bonds with CD73, in addition to hydrophobic stacking interactions.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Biochemistry & Molecular Biology
Yanchun Li, Xinyu Ai, Chunyang Zou, Yutong Liu, Lili Ma, Jinyu Men, Dongyue Liu, Lei Sheng, Xinhui Ruan, Haihan Liu, Weixia Li, Enlong Ma, Lei Yuan
Summary: Researchers have modified the structure of asperphenamate to enhance its inhibitory activity against cathepsin L, with some derivatives showing stronger potency and selectivity, such as B-2a. Additionally, B-2a exhibits significant antimetastatic ability, making it a promising candidate for further studies.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
E. A. Dvoryakova, K. S. Vinokurov, V. F. Tereshchenkova, Y. E. Dunaevsky, M. A. Belozersky, B. Oppert, I. Y. Filippova, E. N. Elpidina
Summary: This study identified two C1 family-specific cysteine cathepsin L enzymes from the larval midgut of the red flour beetle, showing their higher efficiency in hydrolyzing substrates compared to human cathepsin L. Insect digestive cathepsins exhibited higher hydrolysis efficiency towards analogs of immunogenic peptides, which may contribute to therapeutic treatments for autoimmune celiac disease. Bioinformatic and phylogenetic analyses suggest that insect digestive cathepsins are separated from lysosomal cathepsins in the L subfamily.
INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Lidia A. Baltina, Hsueh-Chou Lai, Ya-Chi Liu, Su-Hua Huang, Mann-Jen Hour, Lia A. Baltina, Tagir R. Nugumanov, Sophia S. Borisevich, Leonard M. Khalilov, Svetlana F. Petrova, Sergey L. Khursan, Cheng-Wen Lin
Summary: This study focused on synthesizing a series of nitrogen and sulfur-containing derivatives of Glycyrrhetinic acid as potential inhibitors of Zika virus. Among the compounds tested, four active compounds were identified as effective in inhibiting Zika virus replication, with one compound showing the highest activity. Time-of-addition assays indicated the importance of specific functional groups in inhibiting different stages of the viral life cycle, and molecular docking analysis revealed potential interactions with viral protease enzymes. These findings suggest promising leads for developing new antiviral agents against Zika virus infection.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Physical
Vandana Pandey, Kavita Sharma, Neera Raghav
Summary: This work presents the development, validation, and comparison of three different multi-target artificial neural network models (mt-QSAR) for exploring the quantitative structure-activity relationships of compounds containing carbonyl and thiocarbonyl groups as inhibitors against cysteine proteases. The models were validated using an external test set and showed promising predictive performance. Based on the results, new inhibitors were designed and their activities were predicted. Additionally, molecular docking studies and molecular modeling were conducted to determine the optimal binding conformations and interactions. The findings demonstrate the accuracy and reliability of the proposed models in theoretical predictions.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Plant Sciences
Ze-Yu Zhao, Ying-Peng Tong, Wei Jiang, Yi Zang, Juan Xiong, Jia Li, Jin-Feng Hu
Summary: A preliminaryphytochemical investigation on the 90%MeOH extractfrom the twigs and needles of the vulnerable conifer Keteleeriafortunei led to the isolation and characterization of 17structurally diverse triterpen-26-oic acids, including nine previouslyundescribed ones (fortunefuroic acids A-I, 1-9) featuring a rare furoic acid moiety in the lateral chain. These triterpenoids exhibited dual inhibitory effects against key enzymes for glycolipid metabolism, indicating their potential as new therapeutics for ACL-/ACC1-associated diseases.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Oncology
Narendra Sankpal, Taylor C. Brown, Timothy P. Fleming, John M. Herndon, Anusha A. Amaravati, Allison N. Loynd, William E. Gillanders
Summary: EpCAM is a key protein that inhibits the activity of CTSL in epithelial cancers, and mutations in EpCAM may affect tumor biology processes, leading to tumor cell invasion and metastasis.
Article
Chemistry, Applied
Andre Lucio Franceschini Sarria, Andreia Pereira Matos, Ana Carolina Volante, Antonio Rogerio Bernardo, Gracielle Oliveira Sabbag Cunha, Joao Batista Fernandes, Moacir Rossi Forim, Paulo Cezar Vieira, Maria Fatima das Gracas Fernandes da Silva
Summary: This study demonstrates the insecticidal activity of copper (II) complexes of flavanone derivatives (naringin, naringenin and hesperidin) against Spodoptera frugiperda. Among the tested compounds, complex 9 showed the highest toxicity with a larval mortality rate of 96.66%.
NATURAL PRODUCT RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Roberta Marques Dias de Avila, Leonardo Toffano, Joao Batista Fernandes, Maria Fatima dos Gracas Fernandes da Silva, Lorena Ramos Freitas de Sousa, Paulo Cezar Vieira
Summary: This research investigated the biotransformation of ginger constituents by the pathogenic fungus Colletotrichum gloeosporioides, revealing that oxidation reactions and biphenol dimers formation are key pathways in this process.
BIOCATALYSIS AND BIOTRANSFORMATION
(2022)
Review
Plant Sciences
Maria Fatima das Gracas Fernandes da Silva, Luciano da Silva Pinto, Jessica Cristina Amaral, Danielle Fernandes da Silva, Moacir Rossi Forim, Joao Batista Fernandes
Summary: Through analyzing the metabolic pathways of limonoids and quassinoids, we found discrepancies between the Simaroubaceae and the Rutaceae, and Meliaceae. Meliaceae utilize different biosynthetic pathways leading to more diverse limonoids compared to Rutaceae. Chemical evidence supports the placement of Picramnia species near Cneoroideae genera, showing Picramniaceae is sister to Rutaceae, Simaroubaceae, and Meliaceae.
BRAZILIAN JOURNAL OF BOTANY
(2022)
Article
Chemistry, Multidisciplinary
Maria Clara S. Aguiar, Barbara E. Denadae, Maria Fatima G. F. Silva, Joao B. Fernandes, Paulo R. S. Bittencourt, Fernando R. Scremin, Moacir R. Forim
Summary: Sustainable natural product-based microstructured systems and biopolymers show great potential in crop protection. In this study, lignin and gelatin microcapsules loaded with orange essential oil were developed using spray-drying method to enhance its functionality. The controlled release mechanisms, biological effects, structural and thermal properties were evaluated. Results showed that the type of biopolymer played a crucial role in the quality analysis. The microcapsules loaded with orange essential oil exhibited increased toxicity against Spodoptera frugiperda compared to non-encapsulated oil.
JOURNAL OF THE BRAZILIAN CHEMICAL SOCIETY
(2022)
Review
Entomology
Sean Araujo, Janaina Seibert, Ana Ruani, Ricardo de la Cruz, Artur Cruz, Alana Pereira, Dorai Zandonai, Moacir Forim, Maria Fatima Silva, Odair Bueno, Joao Fernandes
Summary: The most commonly used approach to control leaf-cutting ants is the application of synthetic chemical compounds, but natural substances that attack the symbiotic fungus responsible for the ants' survival may also be effective. This study discusses the potential use of natural substances with fungicidal activity and emphasizes the importance of the symbiosis between the ants and the fungus. Plant species are considered important sources of antifungal compounds, and certain antagonist fungi have been shown to reduce the development of the symbiotic fungus. The use of nanostructured delivery systems is suggested as a new approach for future studies on ant control.
Article
Crystallography
Ignez Caracelli, Wystan K. O. Teixeira, Danilo Yano de Albuquerque, Ricardo S. Schwab, Edward R. T. Tiekink
Summary: The crystal structure data of a compound C14H10IN3 is reported in this study. The crystal belongs to the orthorhombic system with space group P2(1)2(1)2(1). The cell parameters of the compound are a = 8.0778(6) Å, b = 11.1909(10) Å, c = 14.3114(12) Å, and the volume is 1293.72(19) ų.
ZEITSCHRIFT FUR KRISTALLOGRAPHIE-NEW CRYSTAL STRUCTURES
(2022)
Editorial Material
Chemistry, Multidisciplinary
Paulo Cezar Vieira
JOURNAL OF THE BRAZILIAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Edenilson dos Santos Niculau, Douglas Ferreira, Edson Rodrigues-Filho, Franklin Behlau, Rodrigo Facchini Magnani, Leonardo Toffano, Evandro Luis Prieto, Joao Batista Fernandes, Maria Fatima das Gracas Fernandes da Silva
Summary: Citrus canker, a disease that causes serious problems to the citrus industry, can be rapidly diagnosed using MALDI-TOF mass spectrometry combined with chemometric analysis.
Article
Chemistry, Physical
Thales Souza Freire, Ignez Caracelli, Julio Zukerman-Schpector, Ran Friedman
Summary: Gilteritinib is effective in treatment of acute myeloid leukaemia (AML) by inhibiting the FLT3/ITD mutated protein. However, tumour cells develop resistance to gilteritinib due to mutations in the drug target. We used a computer-aided approach to understand the resistance mechanism and found that the mutations F691L and D698N lead to higher activation energy barrier, making mutant enzymes more active. This suggests that tyrosine kinases contribute to resistance against type 1 and type 2 kinase inhibitors.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Ana Calheiros de Carvalho, Caue Santos Lima, Heron Fernandes Vieira Torquato, Andre Tarsis Domiciano, Sebastiao da Cruz Silva, Lucas Magalhaes de Abreu, Miriam Uemi, Edgar Julian Paredes-Gamero, Paulo Cezar Vieira, Thiago Andre Moura Veiga, Livia Soman de Medeiros
Summary: Penicillium setosum is a species with limited information about its metabolic and biological potential. Chemical and biological studies of P. setosum CMLD18 revealed six compounds, one of which displayed promising cytotoxic activity against a human leukemia cell line.
Article
Agricultural Engineering
Gabriel da Silva Amaral, Ricardo Alcantara-de la Cruz, Rodrigo Martinelli, Luiz Renato Rufino Junior, Leonardo Bianco de Carvalho, Fernando Alves de Azevedo, Maria Fatima das Gracas Fernandes da Silva
Summary: Glyphosate resistance was found in multiple weed species in citrus orchards in São Paulo, Brazil, and multiple resistant species were present within the same orchard.
Article
Biochemistry & Molecular Biology
Jose Diogo E. Reis, Paulo Wender P. Gomes, Paulo R. da C. Sa, Sonia das G. S. R. Pamplona, Consuelo Yumiko Y. e Silva, Maria Fatima das G. F. da Silva, Anupam Bishayee, Milton Nascimento da Silva
Summary: This study identified new potential mass spectrometry signatures for phragmalin-type limonoids in Swietenia macrophylla leaves, providing valuable information for future drug development efforts.
Article
Chemistry, Multidisciplinary
Karen Susana M. Madera, Luis Guillermo C. Durango, Orfa Ines C. Martinez, Maria Fatima G. F. da Silva, Joao B. Fernandes, Moacir R. Forim
Summary: This study aimed to determine the relationship between the intestinal microbiota of the cucurbit beetle and its ability to degrade antibiotics. The results revealed that bacterial strains isolated from the gastrointestinal tract of the beetles showed a high degradation rate of doxycycline in media supplemented with the antibiotic.
JOURNAL OF THE BRAZILIAN CHEMICAL SOCIETY
(2023)