Article
Biochemistry & Molecular Biology
Chengqian Wei, Junjie Huang, Yu Wang, Yifang Chen, Xin Luo, Shaobo Wang, Zengxue Wu, Jixiang Chen
Summary: A series of new oxadiazole sulfone derivatives containing an amide moiety were synthesized to screen high-efficiency antibacterial agents for rice bacterial diseases. Compound 10 showed excellent antibacterial activity against Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola, with EC50 values superior to commercial bactericides. Compound 10 demonstrated superior protective and curative activities against rice bacterial leaf blight and rice bacterial leaf streak compared to other tested compounds. Additionally, compound 10 exhibited potential mechanisms of action by affecting extracellular polysaccharides, cell membranes, and enzyme activity of dihydrolipoamide S-succinyltransferase to inhibit the growth of Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Meiling Shen, Lingfeng Li, Yue Li, Xi Gu, Longhui Bai, Chengfeng Xia, Wenyong Xiong, Zhili Zuo
Summary: This study conducted virtual screening of over 1.5 million molecules from the Chemdiv database to identify potential inhibitors of hTRPC5. The screening process evaluated the affinities of the candidates and assessed their inhibitory effects on Ca2+ influx. Two molecules, SML-1 and SML-13, showed significant inhibition of intracellular Ca2+ levels and could potentially be lead compounds for the development of therapeutics targeting hTRPC5 and its associated physiological activities and diseases.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Marion Sisquellas, Marco Cecchini
Summary: PrepFlow is a toolkit for chemical library preparation and management, which efficiently processes compound lists and outputs 3D molecular structures. The tool excels in execution speed, HPC resource utilization, and archiving strategy, significantly improving the efficiency of drug discovery projects.
MOLECULAR INFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Oluwakemi Ebenezer, Maryam A. Jordaan, Nkululeko Damoyi, Michael Shapi
Summary: Noroviruses are non-enveloped viruses causing acute gastroenteritis in humans. The RNA-dependent RNA polymerase is a critical target for developing anti-norovirus agents. Compounds CID-57930781 and CID-44396095 show promising potential as human norovirus inhibitors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Xue-ping Hu, Liu Yang, Xin Chai, Yi-xuan Lei, Md Shah Alam, Lu Liu, Chao Shen, De-jun Jiang, Zhe Wang, Zhi-yong Liu, Lei Xu, Kang-lin Wan, Tian-yu Zhang, Yue-lan Yin, Dan Li, Dong-sheng Cao, Ting-jun Hou
Summary: This study utilized an integrated molecular modeling strategy to identify two lead compounds that could inhibit DprE1 and showed inhibitory activity against Mycobacterium tuberculosis in vitro, with low cytotoxicity against mouse embryo fibroblast NIH-3T3 cells. This research provides an effective strategy for discovering novel anti-TB lead compounds.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Biochemistry & Molecular Biology
Elena M. Loi, Tihomir Tomasic, Cyril Balsollier, Kevin van Eekelen, Matjaz Weiss, Martina Gobec, Matthew G. Alteen, David J. Vocadlo, Roland J. Pieters, Marko Anderluh
Summary: In this study, a novel OGT inhibitor with a uridine mimetic scaffold was identified through virtual screening. The inhibitor showed promising activity in enzyme assays and provides a potential starting point for the development of OGT inhibitors with clinical applications.
Article
Biochemistry & Molecular Biology
Xu Lian, Zhonghua Xia, Xueyao Li, Pavel Karpov, Hongwei Jin, Igor Tetko, Jie Xia, Song Wu
Summary: This study compiled a dataset of 2,3-diaminoquinoxalines, identified a new antibacterial agent, and discovered two new GyrB inhibitors with potential for further development, through chemical synthesis, cheminformatics modeling, and virtual screening.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemical Research Methods
Yue Zhao, Xiang-Gui Wang, Zhong-Ye Ma, Guo-Li Xiong, Zhi-Jiang Yang, Yan Cheng, Ai-Ping Lu, Zhi-Jun Huang, Dong-Sheng Cao
Summary: PARP1 inhibitors are important for ovarian and breast cancer therapies, but current inhibitors have some disadvantages. By employing various virtual screening methods and discovering molecules with novel frameworks, the screening efficiency can be improved, laying the foundation for broader clinical applications.
BRIEFINGS IN BIOINFORMATICS
(2021)
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
Chemistry, Medicinal
Olivia Garland, Anh-Tien Ton, Shoeib Moradi, Jason R. Smith, Suzana Kovacic, Kurtis Ng, Mohit Pandey, Fuqiang Ban, Jaeyong Lee, Marija Vuckovic, Liam J. Worrall, Robert N. Young, Ralph Pantophlet, Natalie C. J. Strynadka, Artem Cherkasov
Summary: Due to the rapid global spread of SARS-CoV-2, there is a need for the development of novel direct-acting antiviral agents. The papain-like protease (PLpro) has been identified as a potential target for these agents. However, drug discovery for PLpro is challenging due to the flexibility and induced-fit effects of its active site.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
Yue Zhang, Jiankun Song, Yuanzhang Zhou, Huijun Jia, Tianyu Zhou, Yingbo Sun, Qiong Gao, Yue Zhao, Yujie Pan, Zhaolin Sun, Peng Chu
Summary: Ubiquitin-specific protease 22 (USP22) plays a prominent role in tumor development and immune reprogramming, and has been proposed as a potential therapeutic target for cancer. Rottlerin and Morusin were discovered as selective and potent USP22 inhibitors, which can increase histone ubiquitination levels and reduce the expression of Sirt1 and PD-L1 proteins. These findings suggest that Rottlerin and Morusin may have potential as drugs for anticancer therapy.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Dongyan Gu, Mengmeng Zhang, Lvtao Cai, Chang Wang, Yu -Bo Zhou, Jia Li, Rong Sheng
Summary: Compound 1 with pyrazolo[1,5-a]quinoxalin-4(5H)-one scaffold was identified as a hit for inhibiting PI3K alpha activity through virtual screening. Structural modifications based on similarity search and molecular docking yielded a novel series of pyrazolo[1,5-a]quinoxalin-4(5H)-one derivatives. The most potent compound 49b exhibited improved PI3K alpha inhibitory activity with good isoform selectivity and demonstrated promising pharmacokinetic properties. Further development of compound 49b as a potential PI3Ka inhibitor is warranted.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Dorota Stary, Jedrzej Kukulowicz, Izabella Goral, Hanna Baltrukevich, Marharyta Barbasevich, Justyna Gody, Marek Bajda
Summary: Thymidine phosphorylase (TP) inhibitors were discovered using multilevel virtual screening, with three compounds showing micromolar biological activity. The study contributes to the development of novel anticancer agents by identifying promising ligands through molecular modeling and in vitro testing.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Review
Biochemistry & Molecular Biology
Alejandro Gomez-Garcia, Jose L. Medina-Franco
Summary: This article reviews the progress in developing compound databases of natural origin, with a focus on chemoinformatic approaches. It also surveys the present state of developing Latin American NP databases and their practical applications in drug discovery.
Article
Biochemistry & Molecular Biology
Bipasa Kar, Chanakya Nath Kundu, Sanghamitra Pati, Debdutta Bhattacharya
Summary: Amid the rise of multi-drug resistance, finding new antibiotics is challenging. This study utilized molecular docking to screen and identify three phytocompounds with potential antimicrobial activity, outperforming the reference drug meropenem. The compounds showed competitive inhibition against the target proteins and demonstrated stability through molecular dynamics simulations. These findings suggest that the phytocompounds have potential as Metallo beta-lactamase inhibitors and warrant further in vitro and in vivo clinical trials.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
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
Timothy B. Dunn, Gustavo M. Seabra, Taewon David Kim, K. Euridice Juarez-Mercado, Chenglong Li, Jose L. Medina-Franco, Ramon Alain Miranda-Quintana
Summary: The quantification of chemical diversity has extensive applications across various fields. With the expansion of chemical libraries, it is crucial to develop efficient methods for quantifying and visualizing the diversity of large-scale chemical libraries. This article introduces a new extended similarity indices method to measure the fingerprint-based diversity of chemical libraries and proposes the Chemical Library Networks (CLNs) framework for visually representing the chemical space of large libraries.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Medicinal
E. Alexis Flores-Padilla, K. Euridice Juarez-Mercado, Jose J. Naveja, Taewon D. Kim, Ramon Alain Miranda-Quintana, Jose L. Medina-Franco
Summary: The importance of epigenetic drug and probe discovery is increasing, aiding in the development of therapeutic treatments and understanding underlying epigenetic mechanisms in biological processes. Through comprehensive analysis of eleven libraries focused on epigenetic targets, guidance is provided for experimental groups working with high-throughput and medium-throughput screening of epigenetic-focused libraries, and as a reference for designing novel focused epigenetic libraries.
MOLECULAR INFORMATICS
(2022)
Article
Chemistry, Multidisciplinary
F. I. Saldivar-Gonzalez, V. D. Aldas-Bulos, J. L. Medina-Franco, F. Plisson
Summary: Natural products are considered privileged structures to interact with protein drug targets, sparking interest in developing NP-inspired medicines. The advancement of artificial intelligence has democratized the field of natural product drug discovery, with the introduction of natural language processing and machine learning algorithms enhancing molecular design and target selectivity.
Article
Biochemistry & Molecular Biology
Diana Castro-Vazquez, Jessica Nayelli Sanchez-Carranza, Laura Alvarez, Karina Euridice Juarez-Mercado, Noberto Sanchez-Cruz, Jose L. Medina-Franco, Mayra Antunez-Mojica, Leticia Gonzalez-Maya
Summary: Phenolic acids play an important role in epigenetic regulation, particularly as inhibitors of DNA methylation. In this study, a series of methyl benzoate and cinnamate analogs were synthesized and evaluated for their cytotoxic activity and DNA methylation inhibition. The results showed that certain analogs exhibited strong cytotoxicity and DNA methylation inhibition.
CHEMICAL BIOLOGY & DRUG DESIGN
(2022)
Review
Pharmacology & Pharmacy
Jose L. Medina-Franco, Edgar Lopez-Lopez, Emma Andrade, Lena Ruiz-Azuara, Angelo Frei, Davy Guan, Johannes Zuegg, Mark A. T. Blaskovich
Summary: Metallodrug discovery has made significant progress, but there is currently no dedicated public compound database. Establishing a metallodrug compound database would greatly facilitate the discovery and development of metallodrugs.
DRUG DISCOVERY TODAY
(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
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.
