Article
Chemistry, Inorganic & Nuclear
Dameng Sun, Xin Huang, Ruojun Man, Xinjie Jia, Xinluan Song, Sihan Wang, Xingyong Xue, Hongming Liu, Zhen Ma
Summary: A series of Fe(ii) complexes were synthesized using modified terpyridine ligands, and they exhibited high antiproliferation activities against human cancer cell lines with low toxicity to normal cells. The carboxyl-modified complex showed significant selectivity in killing hepatoma cancer cells. These Fe(ii) complexes have potential as anticancer drugs against hepatoma cancer.
DALTON TRANSACTIONS
(2023)
Article
Biochemistry & Molecular Biology
Yanhong Liu, Linsheng Zhang, Maochao Guo, Liu Chen, Baixing Wu, Hongda Huang
Summary: The study reveals that phages have evolved Aca1 and Aca2 proteins to inhibit host CRISPR-Cas systems by binding to acr-aca promoters. The structural basis for the repression roles of Aca proteins is elucidated, shedding light on the repression roles of other Aca family proteins and the autoregulation roles of acr-aca operons.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Chemistry, Applied
Marwa Zekrallah, Mahmoud M. Mashaly, Mona Saif, Rania Fouad
Summary: This study fabricates and analyzes the newly synthesized Cu(AHC)(2) complex to investigate its biological functionalities including cytotoxicity, DNA binding, and DNA cleavage. The results show that the Cu(AHC)(2) complex exhibits excellent cytotoxicity against HepG-2 cell line and strongly binds to DNA through intercalative mode, with the ability to destroy DNA.
APPLIED ORGANOMETALLIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Terri D. Bryson, Pablo De Ioannes, Marco Igor Valencia-Sanchez, Jorja G. Henikoff, Paul B. Talbert, Rachel Lee, Bernard La Scola, Karim-Jean Armache, Steven Henikoff
Summary: The chromatin organization of Marseillevirus differs fundamentally from that of eukaryotes, with distinct modes of DNA packaging by histones. The doublet histones in Marseillevirus play a crucial role in viral genome protection and may represent an early stage of histone differentiation.
Article
Biochemistry & Molecular Biology
Bilge Bicak, Serda Kecel Gunduz, Yasemin Budama Kilinc, Petra Imhof, Bahar Gok, Gizem Akman, Aysen E. Ozel
Summary: The study investigated the molecular structure and DNA binding interaction of the YKT tripeptide using various in silico, spectroscopic, and in vitro methods. The study's findings may pave the way for the development of various cancer drugs.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Inorganic & Nuclear
Bai-Hua Chen, Zheng-Yin Pan, Wen-Wen Feng, Qi-Yan Liu, Yingju Liu, Liang He
Summary: In this study, two novel copper(II) complexes containing a beta-carboline derivative and amino acids were designed and synthesized. Both complexes bind to DNA and exhibit good affinity for human serum albumin. Moreover, the antitumor activity of these complexes against various cancer cells is significantly superior to that of cisplatin. The study also provides insights into the anticancer mechanism of the complexes, which involve apoptosis induction through mitochondrial damage, oxidative stress, and activation of the caspase protein family. This research highlights the potential of copper-based therapeutics by incorporating aromatic heterocyclic alkaloid ligands and water-soluble amino acid ligands into copper complexes.
DALTON TRANSACTIONS
(2023)
Article
Chemistry, Inorganic & Nuclear
P. Jyothi, V. Sumalatha, D. Rajitha
Summary: Three Co(II) complexes were synthesized and characterized, showing good DNA binding, antimicrobial, and anticancer activities.
INORGANIC CHEMISTRY COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Karthik Murugan, Shravanti K. Suresh, Arun S. Seetharam, Andrew J. Severin, Dipali G. Sashital
Summary: Cas9 variants differ in their cleavage rates and ability to create double-strand breaks at targets with multiple mismatches, which may contribute to the variations in specificities observed in genome editing studies.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Chemistry, Physical
Sabeel M. Basheer, Puthiyavalappil Rasin, Saravana Loganathan Ashok Kumar, Moorthy Saravana Kumar, Anandaram Sreekanth
Summary: 2-acetylpyrzine N-(4)-cyclohexylthiosemicarbazide (H2L) and its Ni(II) and Fe(III) metal complexes were synthesized and studied for their interactions with Bovine Serum Albumin and CT-DNA. The complexes exhibited high affinity for DNA and showed non-covalent intercalation.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Biochemistry & Molecular Biology
A. Sakthivel, B. Thangagiri, N. Raman, J. Joseph, Ramu Guda, Mamatha Kasula, L. Mitu
Summary: Novel macrocyclic Schiff base complexes with different metal ions have been synthesized and characterized, showing promising antioxidant, antimicrobial, and anticancer activities. The interaction of the complexes with DNA through the macrocyclic ligand and the inhibitory effects on target proteins such as EGFR and HER2 have been investigated and demonstrated.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Biochemistry & Molecular Biology
Yu-Mei Chen, Yu -Can Liu, Jin-Quan Wang, Guang-Chuan Ou, Xiao-Feng Wang, Shu-Qin Gao, Ke-Jie Du, Ying-Wu Lin
Summary: Four copper(II) complexes strongly interact with DNA through partial intercalation and cleave DNA through the generation of singlet oxygen (1O2). In vitro experiments show that these complexes exhibit significant anticancer activity and induce apoptosis in HeLa cells as demonstrated by AO/EB staining.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
A. Vijayaraj, R. Prabu, R. Suresh, R. Sangeetha Kumari, V. Kaviyarasan, V. Narayanan, P. Tamizhdurai, V. L. Mangesh, Fatmah Ali Alasmary, Umamaheswari Rajaji, Mani Govindasamy
Summary: This study reports the characterization of several d-f heterobinuclear [GdCuL1-5(bpy)2(NO3)2] complexes based on 2,2'-bipyridyl ligands using spectroscopy and elemental analysis. The complexes were investigated for their luminescence, genetic code properties, catalytic activity, magnetism, and breaking attributes. The [GdCuL1-5(bpy)2(NO3)2] complexes exhibited two one-electron irreversible reduction events and showed ferromagnetic coupling. The inceptive rate of progress for oxidizing 1,2-benzenediol to cyclohexa-3,5-diene-1,2-dione was higher for longer chain complexes. The [GdCuL5(bpy)2(NO3)2] and [GdCuL4(bpy)2(NO3)2] complexes showed strong DNA genetic code properties, and the complexes exhibited singlet oxygen-mediated oxidative rift of circular recombinant plasmid pBR322 cloning vector in the presence of 2-sulfanylethanol.
ARABIAN JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Analytical
Shiyi Xie, Benfeng Xu, Rui Tang, Siyu Chen, Chunyang Lei, Zhou Nie
Summary: In this study, the CRISPR/Cas12a system was utilized as a direct sensing system for Mn2+ detection in living cells. It was found that Mn2+ can accelerate the cleavage kinetics of Cas12a, allowing for robust detection of Mn2+ in complex biological samples and in the cytoplasm of living cells. The system was also applied to study the cytotoxicity of Mn2+ in nerve cells.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Shazia Parveen, Farukh Arjmand, Qianfan Zhang, Musheer Ahmad, Arif Khan, Loic Toupet
Summary: In this study, the synthesis and single crystal X-ray structure of Cu(II)-picolinic acid complex, 1 as a potent topoisomerase I inhibitor was reported. Biochemical studies revealed the complex's higher binding propensity towards tRNA, significant inhibitory effect on enzyme catalytic activity, and strong antimicrobial potential. Additionally, DFT and molecular docking studies provided insights into electronic transitions and specific binding preferences at the target site.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Chemistry, Physical
Aveli Rambabu, Sreenu Daravath, Dasari Shiva Shankar, Shivaraj
Summary: The two mononuclear metal complexes bind to DNA through an intercalation mode and exhibit good cleavage ability under oxidative and photolytic conditions. Both complexes show marked biocidal potential in vitro.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Article
Cell Biology
Emmanuel Heilmann, Francesco Costacurta, Seyed Arad Moghadasi, Chengjin Ye, Matteo Pavan, Davide Bassani, Andre Volland, Claudia Ascher, Alexander Kurt Hermann Weiss, David Bante, Reuben S. Harris, Stefano Moro, Bernhard Rupp, Luis Martinez-Sobrido, Dorothee von Laer
Summary: Protease inhibitors are effective antiviral drugs, and Nirmatrelvir is the first protease inhibitor developed specifically against the SARS-CoV-2 protease 3CLpro. By using a chimeric vesicular stomatitis virus (VSV), researchers identified mutations that confer resistance to nirmatrelvir.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Chemistry, Medicinal
Denise Sighel, Giulia Battistini, Emanuele Filiberto Rosatti, Jacopo Vigna, Matteo Pavan, Romina Belli, Daniele Peroni, Federica Alessandrini, Sara Longhi, Michael Pancher, Joanna Rorbach, Stefano Moro, Alessandro Quattrone, Ines Mancini
Summary: New therapeutic strategies are needed for glioblastoma treatment, with a focus on glioblastoma stem cells (GSCs). Inhibition of mitochondrial translation has been identified as a potential target for GSCs, and the combination of streptogramins B and A antibiotics has shown promise in vitro. This study used docking calculations to develop new streptogramin A derivatives and evaluated their ability to suppress GSC growth and inhibit mitochondrial translation. The fluorine derivatives of dalfopristin and virginiamycin M1 were found to be more potent and penetrate cells to a greater extent, suggesting their potential as antineoplastic agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Annagiulia Favaro, Giovanni Bolcato, Marcelo A. A. Comini, Stefano Moro, Massimo Bellanda, Mattia Sturlese
Summary: Researchers conducted two different screenings for the peculiar redox system of Trypanosoma brucei parasite and discovered a small molecule that binds at the glutathione binding site. This finding represents an important step in developing a new strategy to interfere with the Trypanosoma Brucei redox system, potentially shedding light on the perturbation of this biochemical machinery and offering novel therapeutic possibilities.
Article
Microbiology
Marta Celegato, Mattia Sturlese, Vivian Vasconcelos Costa, Marta Trevisan, Angelica SamerLallo Dias, Ingredy Beatriz Souza Passos, Celso Martins Queiroz-Junior, Lorenzo Messa, Annagiulia Favaro, Stefano Moro, Mauro Martins Teixeira, Arianna Loregian, Beatrice Mercorelli
Summary: This study identifies two small molecules with pan-flavivirus antiviral potential through virtual screening of over 1 million compounds. The molecules inhibit the replication of dengue virus, Zika virus, and West Nile virus, and show efficacy in a mouse model of dengue.
Article
Chemistry, Medicinal
Teresa Gianferrara, Matteo Pavan, Davide Bassani, Fabrizio Vincenzi, Silvia Pasquini, Giovanni Bolcato, Katia Varani, Giampiero Spalluto, Stephanie Federico, Stefano Moro
Summary: Traditionally, molecular recognition between adenosine receptors and their ligands has been thought to occur with a 1:1 stoichiometry. However, recent simulations suggest an alternative 2:1 binding stoichiometry. In this study, a bis-ribosyl adenosine derivative, BRA1, was synthesized and tested for its binding and activation abilities on adenosine receptors, with molecular modeling used to rationalize its activity.
Article
Biochemistry & Molecular Biology
Andrea Dodaro, Matteo Pavan, Stefano Moro
Summary: The latest outbreak of monkeypox virus in 2022 highlights the potential threat it poses to public health. Due to the lack of specific treatments, the monkeypox virus I7L protease has been identified as a potential target for the development of new drugs. Through computational modeling and virtual screening, 14 potential inhibitors of the monkeypox I7L protease have been identified.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Daniela Carbone, Michele De Franco, Camilla Pecoraro, Davide Bassani, Matteo Pavan, Stella Cascioferro, Barbara Parrino, Girolamo Cirrincione, Stefano Dall'Acqua, Stefano Moro, Valentina Gandin, Patrizia Diana
Summary: A library of 3-amino-1,2,4-triazine derivatives was designed and synthesized, which showed potent and selective inhibition of PDK. These compounds proved to be effective in inducing cancer cell death, especially in human pancreatic KRAS mutated cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Matteo Pavan, Stefano Moro
Summary: Since its outbreak in December 2019, the COVID-19 pandemic has caused a global crisis, with millions of deaths. The urgency of finding suitable drugs has highlighted the importance of computer simulations in drug design. This study provides an overview of the pandemic, discusses drug management efforts, and explores the role of computer-aided drug discovery techniques in facing present and future pandemics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Daniela Carbone, Michele De Franco, Camilla Pecoraro, Davide Bassani, Matteo Pavan, Stella Cascioferro, Barbara Parrino, Girolamo Cirrincione, Stefano Dall'Acqua, Stefania Sut, Stefano Moro, Valentina Gandin, Patrizia Diana
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer type with poor prognosis and drug resistance. Cell metabolism alteration plays a key role in PDAC progression, leading to cell proliferation, invasion, and chemotherapy resistance. In this study, a new series of indolyl-7-azaindolyl triazine compounds were synthesized, inspired by marine bis-indolyl alkaloids. These compounds were found to inhibit the enzymatic activity of pyruvate dehydrogenase kinases (PDKs), with a high selectivity against KRAS-mutant PDAC. Molecular docking analysis and cell growth inhibition assays demonstrated the potential of these derivatives as therapeutic options for PDAC.
Review
Biochemistry & Molecular Biology
Davide Bassani, Stefano Moro
Summary: The use of computational approaches in drug discovery, known as computer-aided drug design (CADD), has become a crucial component in pharmaceutical discovery pipelines. CADD techniques have significantly improved the efficiency of early discovery steps, facilitating the selection of appropriate compounds from a vast chemical space. Furthermore, CADD methods rationalize the biochemical and interactive processes at the molecular level, allowing for rational 3D design and optimization of chemical entities. This review provides an overview of CADD methods, highlighting their potential applications, benefits, limitations, and weaknesses in various scenarios of pharmaceutical and biological interest.
Article
Microbiology
Valerio Taverniti, Hanna Krynska, Assunta Venuti, Marie-Laure Straub, Cecilia Sirand, Eugenie Lohmann, Maria Carmen Romero-Medina, Stefano Moro, Alexis Robitaille, Luc Negroni, Denise Martinez-Zapien, Murielle Masson, Massimo Tommasino, Katia Zanier
Summary: The study reveals a direct interaction between delta Np73 alpha and the E2F4/p130 complex, which is involved in cell cycle control. This interaction may result in the rewiring of the E2F4/p130 transcriptional program, leading to oncogenesis.
Article
Oncology
Chiara Bertagnin, Lorenzo Messa, Matteo Pavan, Marta Celegato, Mattia Sturlese, Beatrice Mercorelli, Stefano Moro, Arianna Loregian
Summary: HPV-induced cancers are a major global health issue and lack specific therapeutic regimens. In this study, researchers identified a compound that could inhibit the interaction between the E7 protein and PTPN14, leading to a reduction in viability, proliferation, migration, and cancer-stem cell potential of HPV-positive cervical cancer cells. This compound also showed activity against cervical cancer cells transformed by different high-risk HPV genotypes, suggesting a potential broad-spectrum activity.
Article
Chemistry, Medicinal
Deborah Palazzotti, Tommaso Felicetti, Stefano Sabatini, Stefano Moro, Maria Letizia Barreca, Mattia Sturlese, Andrea Astolfi
Summary: The superbug Staphylococcus aureus (S.aureus) exhibits various resistance mechanisms, such as efflux pumps, which greatly contribute to antimicrobial resistance. The NorA efflux pump activity is particularly associated with S. aureus resistance to fluoroquinolone antibiotics (e.g., ciprofloxacin) by actively extruding them from cells. Efflux pump inhibitors (EPIs) can increase antibiotic concentrations in bacteria and restore their susceptibility, offering a promising strategy against bacterial resistance. The recent release of NorA efflux pump cryo-electron microscopy (cryo-EM) structures in complex with synthetic antigen-binding fragments (Fabs) represents a significant breakthrough in studying S. aureus antibiotic resistance. Combined molecular dynamics and docking experiments were used to investigate the molecular mechanisms behind the interaction between NorA and EPIs, aiming to elucidate how the NorA efflux pump recognizes its inhibitors. The findings provide insights into the dynamic NorA-EPI interactions and lay the foundation for future drug discovery efforts to combat antimicrobial resistance.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Correction
Biochemistry & Molecular Biology
Davide Bassani, Stefano Moro
Article
Biochemistry & Molecular Biology
Veronica Salmaso, Margherita Persico, Tatiana Da Ros, Giampiero Spalluto, Sonja Kachler, Karl-Norbert Klotz, Stefano Moro, Stephanie Federico
Summary: This study investigates the structural features of ligands leading to affinity and/or selectivity at adenosine receptors. The findings suggest that bulky acyl moieties at position N5 and small alkyl groups at position N8 are associated with affinity and selectivity at the A(3) receptor. Meanwhile, a free amino function at the 5 position induces high affinity at the A(2A) and A(1) receptors.
