Article
Chemistry, Medicinal
Junhui Park, Gaeun Sung, SeungHyun Lee, SeungHo Kang, ChunKyun Park
Summary: The paper explores the activity cliff phenomenon in drug-target interactions and introduces a graph convolutional network model for predicting activity cliffs, showing superiority in comparison to other methods for popular target datasets. Additionally, the use of gradient-weighted class activation mapping is demonstrated to visualize activation weights at nodes in molecular graphs, potentially aiding in the identification of important substructures for molecular docking.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Medicinal
Anna Sampietro, F. Javier Perez-Areales, Paula Martinez, Elsa M. Arce, Carles Galdeano, Diego Munoz-Torrero
Summary: Research on multitarget anti-Alzheimer agents has seen a rapid increase in publications, with China, Italy, and Spain being the leading countries in this field. The scopolamine-induced amnesia mouse model is commonly used in in vivo studies, and there are variations in research trends among different countries.
Article
Chemistry, Medicinal
Min-Jeong Kim, Sarita Pandit, Jun-Goo Jee
Summary: This study predicts dual inhibitors for kinase and carbonic anhydrase using machine learning techniques and validates their efficacy through biochemical and biophysical experiments. The results show potent inhibitory activities of certain kinase and carbonic anhydrase inhibitors, and provide evidence of their direct interaction with the respective proteins.
Article
Biochemistry & Molecular Biology
Kaiyang Liu, Xi Chen, Yue Ren, Chaoqun Liu, Tianyi Lv, Ya'nan Liu, Yanling Zhang
Summary: Polypharmacology has emerged as a new paradigm in drug discovery, playing a crucial role in addressing polygenic diseases. This paper introduces multi-target-based polypharmacology prediction (mTPP), an approach that employs virtual screening and machine learning to explore the relationship between the action of multiple targets and the overall efficacy of drugs. Through the mTPP model, potential hepatoprotective components and candidates with potential effects against drug-induced liver injury (DILI) are identified. The model demonstrates accuracy in predicting the viabilities of APAP-induced injury cells, indicating its potential for aiding the development of polypharmacology and the discovery of multi-target drugs.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Biochemistry & Molecular Biology
Sugandh Kumar, Bharati Singh, Pratima Kumari, Preethy Kumar, Geetanjali Agnihotri, Shaheerah Khan, Tushar Kant Beuria, Gulam Hussain Syed, Anshuman Dixit
Summary: This study utilized bioinformatics techniques to screen FDA approved drugs against SARS-CoV2 proteins and identified 74 molecules that can bind to various SARS-CoV2 and human host proteins, with some showing good activity against SARS-CoV2. Experimental validation using vero E6 cells infected with SARS-CoV2 virus showed promising results, suggesting that these studies may help in developing new therapeutic options for COVID-19 treatment.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Filipe G. A. Estrada, Silvia Miccoli, Natalia Aniceto, Alfonso T. Garcia-Sosa, Rita C. Guedes
Summary: Multiple myeloma is an incurable plasma cell neoplastic disease, and overcoming treatment resistance may require a polypharmacology approach such as combination therapy and multitargeting drugs.
Article
Chemistry, Medicinal
Wenqing Zhang, Kan Li, Tianqi Wang, Ming Wu, Linli Li
Summary: This study identified seven JMJD7 inhibitors using consensus docking/scoring strategy and bioactivity evaluation, with Cpd-3 being the most potent compound showing efficient binding to JMJD7 in vitro and displaying good inhibitory activity against cancer cell lines expressing high levels of JMJD7. Overall, this research provided a solid foundation for drug discovery targeting JMJD7.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Dong-Jun Fu, Ting Wang
Summary: In this study, a series of potential dual tubulin-NEDDylation inhibitors were synthesized and evaluated. Compound C11 exhibited the strongest antiproliferative activity and showed potent inhibition against tubulin and NEDDylation.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Food Science & Technology
Gabriela Cristina Soares Rodrigues, Mayara dos Santos Maia, Andreza Barbosa Silva Cavalcanti, Renata Priscila Costa Barros, Luciana Scotti, Carlos L. Cespedes-Acuna, Eugene N. Muratov, Marcus Tullius Scotti
Summary: Pesticides are commonly used to control insects and pests, but the overuse can have negative effects, leading to the search for natural alternatives. This study aimed to identify natural products with insecticidal potential against specific pests, utilizing QSAR models and molecular docking to prioritize promising compounds.
FOOD AND CHEMICAL TOXICOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Luca Pinzi, Francesca Foschi, Michael S. Christodoulou, Daniele Passarella, Giulio Rastelli
Summary: The design of multi-target ligands is a promising approach for cancer treatment, showing synergistic effects by simultaneously inhibiting Hsp90 and B-Raf, while also moderately inhibiting PDHK1 kinase activity. Experimental validation indicates that the designed compounds have potential therapeutic value by potently inhibiting Hsp90. Molecular dynamics simulations provide further insights into the multi-target activity of these compounds.
Article
Chemistry, Medicinal
Viviane Correa Santos, Paulo Gaio Leite, Lucianna Helene Santos, Pedro Geraldo Pascutti, Peter Kolb, Fabiana Simao Machado, Rafaela Salgado Ferreira
Summary: Existing treatments for Chagas disease have limited efficacy and side effects, leading to the search for novel treatments. Compound 8 and compound 22, which target the cysteine protease cruzain, show potential for treating Chagas disease and could serve as drug candidates.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Zihni Onur Caliskaner
Summary: Genome methylation plays a crucial role in various biological events, and its crosstalk with gene expression is mediated by MBD2. However, there is a limited number of small molecules that can be used as inhibitors for MBD2. In this study, we screened a compound library and identified two promising candidates, CID3100583 and 8,8-ethylenebistheophylline, which have the potential to disrupt MBD2-DNA interaction.
JOURNAL OF MOLECULAR MODELING
(2022)
Review
Biochemistry & Molecular Biology
Ann Wang, Jacob D. Durrant
Summary: This article outlines the importance of open-source, accessible tools for computer-aided drug discovery (CADD) and proposes a browser-based approach to CADD tool deployment. The advantages and need for browser apps are highlighted.
Article
Biochemistry & Molecular Biology
Renata Priscila Barros de Menezes, Jessika de Oliveira Viana, Eugene Muratov, Luciana Scotti, Marcus Tullius Scotti
Summary: This study combined ligand-based and structure-based virtual screening techniques to select five potentially active alkaloids against S. mansoni. Two of these alkaloids showed plausible toxicity, metabolomics, and toxicity profiles, making them promising candidates for the development of new schistosomicidal compounds based on natural products.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jose L. Medina-Franco, Edgar Lopez-Lopez, Liliam P. Martinez-Fernandez
Summary: This study reports two quinazoline-based derivatives with strong inhibitory activity against DNMT1, low affinity for DNMT3A, and no inhibition of DNMT3B. These compounds have low cell toxicity and effectively inhibit G9a.
Article
Biochemistry & Molecular Biology
Jose L. Medina-Franco, Norberto Sanchez-Cruz, Edgar Lopez-Lopez, Barbara Diaz-Eufracio
Summary: The concept of chemical space is crucial in chemoinformatics, particularly in drug design and discovery. Molecular representation plays a key role in defining chemical space and exploring structure-property relationships. Freely available tools are important for advancing research and education in this field.
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
(2022)
Article
Chemistry, Medicinal
Edgar Lopez-Lopez, Carlos M. Cerda-Garcia-Rojas, Jose L. Medina-Franco
Summary: Modification of the tubulin-microtubule system has led to effective strategies for cancer treatment. However, many inhibitors of this system are based on limited structural innovation. This study aims to develop a screening protocol for natural products to identify new potential inhibitors of the tubulin-microtubule system.
MOLECULAR INFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Edgar Lopez-Lopez, Jose L. Medina-Franco
Summary: Drug-induced liver injury (DILI) is a major obstacle in drug development and approval, with animal models, liver function tests, and chemical properties being crucial for understanding and preventing DILI events. This study implements data fusion to analyze DILI events by considering different criteria simultaneously, highlighting the importance of in vitro and chemical data analysis for improving our understanding of DILI.
Article
Chemistry, Medicinal
Timothy B. Dunn, Edgar Lopez-Lopez, Taewon David Kim, Jose L. Medina-Franco, Ramon Alain Miranda-Quintana
Summary: "Understanding structure-activity landscapes" emphasizes the importance of the relationship between molecular structure and activity in drug discovery, and highlights the impact of activity cliffs on design and prediction. This study aims to use n-ary indices and the medoid algorithm to rapidly and efficiently quantify the structure-activity landscapes of large compound data sets, and explore the optimal correlations between similarity measures and structure-activity rankings. The applicability of these methods is demonstrated by analyzing 10 compound data sets with pharmaceutical relevance using different fingerprints, similarity indices, and coincidence thresholds.
MOLECULAR INFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Kenneth Lopez-Perez, Edgar Lopez-Lopez, Jose L. Medina-Franco, Ramon Alain Miranda-Quintana
Summary: Visualization of chemical space is crucial in various aspects of chemistry, such as compound library design and exploring structure-property relationships. ChemMaps is a visualization methodology that approximates compound distribution in large datasets based on satellite compounds with a similar mapping. Extended similarity indices are proposed to identify relevant regions and reduce high-dimensional data in describing a library's chemical space.
Review
Biochemistry & Molecular Biology
Cesar A. Zaa, alvaro J. Marcelo, Zhiqiang An, Jose L. Medina-Franco, Marco A. Velasco-Velazquez
Summary: Anthocyanins, a type of flavonoid, possess potent antioxidant properties and can penetrate the blood-brain barrier, exhibiting neuroprotective effects. Including anthocyanin-rich foods in the diet has been shown to lower the risk of neurodegenerative diseases, as their antioxidant, anti-inflammatory, and anti-apoptotic properties contribute to neuroprotection, particularly in Alzheimer's and Parkinson's diseases.
Article
Chemistry, Multidisciplinary
Raziel Cedillo-Gonzalez, Jose L. Medina-Franco
Summary: This study explores, characterizes, and analyzes the chemical space of 409 G9a inhibitors reported in a large public database. It quantifies the structural diversity of G9a inhibitors and compares them with commercial libraries focused on epigenetic targets. The findings will contribute to the development of predictive models for identifying G9a inhibitors and highlight the importance of screening commercial libraries to expand the relevant chemical space.
Article
Chemistry, Medicinal
Alejandro Gomez-Garcia, Daniel A. Acuna Jimenez, William J. Zamora, Haruna L. Barazorda-Ccahuana, Miguel A. Chavez-Fumagalli, Marilia Valli, Adriano D. Andricopulo, Vanderlan da S. Bolzani, Dionisio A. Olmedo, Pablo N. Solis, Marvin J. Nunez, Johny R. Rodriguez Perez, Hoover A. Valencia Sanchez, Hector F. Cortes Hernandez, Jose L. Medina-Franco
Summary: The Latin American Natural Products Database (LANaPDB) is a public compound collection that gathers chemical information of natural products from various databases in Latin America. The current version includes chemical structures from six countries, with terpenoids, phenylpropanoids, and alkaloids being the most abundant compounds. LANaPDB covers a wide chemical space and many compounds exhibit drug-like properties.
Article
Biochemistry & Molecular Biology
Francisco J. Barrera-Tellez, Fernando D. Prieto-Martinez, Alicia Hernandez-Campos, Karina Martinez-Mayorga, Rafael Castillo-Bocanegra
Summary: A computational study was conducted to assess the druggability of TryR from L. mexicana using structure-based approaches. Three relevant pockets were identified, with the sigma-site showing the most promise as a drug target.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Edgar Lopez-Lopez, Oscar Robles, Fabien Plisson, Jose L. Medina-Franco
Summary: Peptide structure-activity/property relationship (P-SA/PR) studies aim to understand how the structural variations of peptides influence their biological activities and other functional properties, accelerating the rational design and optimization of peptide-based drugs, biomaterials, or diagnostic agents. This study used the MAP4 fingerprint to analyze the structure-activity relationship of 223 antimicrobial peptides against methicillin-resistant Staphylococcus aureus (MRSA), identifying critical residues and structural motifs that play a crucial role in the anti-MRSA activity of the peptides.
Review
Chemistry, Multidisciplinary
Conrad V. Simoben, Smith B. Babiaka, Aurelien F. A. Moumbock, Cyril T. Namba-Nzanguim, Donatus Bekindaka Eni, Jose L. Medina-Franco, Stefan Guenther, Fidele Ntie-Kang, Wolfgang Sippl
Summary: The use of traditional medicine has a long history and is still relied upon by many, especially in developing or underprivileged communities. In silico-based methods have played a crucial role in drug discovery, particularly in identifying natural product-based candidates. However, there are challenges in identifying and proposing novel natural product-based hits.
