Review
Multidisciplinary Sciences
David J. Newman
Summary: This review covers the recent history of important natural products and their derivatives in the areas of anti-infectives, cancer treatments, and diabetes drugs, highlighting the involvement of Mother Nature in the discovery of these approved drugs.
NATIONAL SCIENCE REVIEW
(2022)
Article
Food Science & Technology
Haopeng Dai, Min He, Guilin Hu, Zhongrong Li, Abdulbaset Al-Romaima, Zhouwei Wu, Xiaocui Liu, Minghua Qiu
Summary: The study aimed to investigate the ACE inhibitory effect of bioactive peptides from green coffee beans. Through in vitro and in silico methods, it was found that two peptides have the potential to be used as antihypertensive agents.
Article
Chemistry, Medicinal
Ryuichiro Ishitani, Toshiki Kataoka, Kentaro Rikimaru
Summary: The automatic design of molecules with specific chemical and biochemical properties is crucial in material informatics and computational drug discovery. This study introduces a novel representation of molecules, called Reversible Junction Tree (RJT), which can be converted back to the original molecule without external information. By utilizing deep reinforcement learning, the molecular design and optimization problem is formulated as a tree-structure construction, enabling efficient optimization in simple benchmark tasks. The applicability of the method is further demonstrated in multiobjective optimization and fine-tuning of reinforcement learning models in drug discovery.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Medicinal
Bin Sun, Yating Liu, Haiyan Fan, Yunfei An, Wenxia Liu, Qingpeng Wang, Jun Han
Summary: In this study, a CYP53 homology model was constructed and the active region was analyzed. Based on this model, novel CYP53 inhibitors were designed and synthesized. The results showed that two of the compounds exhibited excellent biological activity against pathogenic and drug-resistant fungi, potentially by inhibiting CYP53 activity and blocking the metabolism of toxic intermediates (benzoates).
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Santanu Sasidharan, Neellohit Sarkar, Prakash Saudagar
Summary: This review discusses the potential targets of SARS-CoV-2 at the genomic and proteomic levels, as well as the compounds that inhibit these targets. The role of the ACE-2 receptor and the current status of drugs in clinical trials and vaccines are also examined.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Cardiac & Cardiovascular Systems
Jonas Ghouse, Vinicius Tragante, Ayesha Muhammad, Gustav Ahlberg, Morten W. Skov, Dan M. Roden, Ingileif Jonsdottir, Laura Andreasen, Pia Rengtved Lundegaard, Linea C. Trudso, Karina Banasik, Soren Brunak, Sisse R. Ostrowski, Christian Torp-Pedersen, Ole Pedersen, Erik Sorensen, Lars Kober, Kasper Iversen, Unnur Thorsteinsdottir, Gudmundur Thorgeirsson, Henrik Ullum, Daniel F. Gudbjartsson, Jonathan D. Mosley, Hilma Holm, Kari Stefansson, Henning Bundgaard, Morten Salling Olesen
Summary: This study conducted a genome-wide association study to identify genetic variants associated with ACE-inhibitor (ACEi) drug discontinuation and adverse drug reactions (ADRs). It identified seven genetic loci associated with ACEi discontinuation, with a strong association between ACEi discontinuation and ACEi-associated cough. These findings provide insight into the pathophysiology of ACEi-associated ADRs.
EUROPEAN HEART JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Sunday N. Okafor, Pavimol Angsantikul, Hashim Ahmed
Summary: This research utilized computational tools to screen a large compound library and identified potential HIV-1 protease inhibitors. Two optimized molecules showed promising activity and should be further investigated in vitro and in clinical trials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Eman Z. Elrazaz, Rabah A. T. Serya, Nasser S. M. Ismail, Amgad Albohy, Dalal A. Abou El Ella, Khaled A. M. Abouzid
Summary: The study reports the design, synthesis, and evaluation of a series of 4-substituted thieno[2,3-d]pyrimidine derivatives as VEGFR-2 inhibitors, showing potent inhibitory activities against VEGFR-2. Molecular docking analysis and molecular dynamics simulation were conducted to further investigate the findings, indicating the potential of these compounds as therapeutic agents.
BIOORGANIC CHEMISTRY
(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
Agriculture, Multidisciplinary
Zihan Wang, Hongbing Fan, Xiaoyu Bao, Jianping Wu
Summary: This study aims to investigate if ACE-inhibitory (ACEi) peptides can also activate ACE2. Among the 200 peptides screened, peptides IKW and RIY showed significant antihypertensive activity and activated ACE2, while IQY only increased Ang(1-7) level without affecting ACE and ACE2. Peptides MAW and MRW did not have any effect on blood pressure, ACE, and ACE2. The activation of ACE2 is not a common feature of ACEi peptides.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Guo-Li Xiong, Yue Zhao, Lu Liu, Zhong-Ye Ma, Ai-Ping Lu, Yan Cheng, Ting-Jun Hou, Dong-Sheng Cao
Summary: Scaffold hopping is a central task in modern medicinal chemistry, and the computational bioactivity fingerprint (CBFP) facilitates easier scaffold hopping to discover novel biologically active compounds. CBFP shows outstanding performance in retrospective benchmarks and prospective validation, making it a promising tool for exploring uncharted chemical space and discovering potential new compounds.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Rex Devasahayam Arokia Balaya, Jaikanth Chandrasekaran, Saptami Kanekar, Prashant Kumar Modi, Shobha Dagamajalu, Kirthika Gopinathan, Rajesh Raju, T. S. Keshava Prasad
Summary: The CAMKK2 is crucial in regulating intracellular calcium levels and signaling pathways, and dysregulation of its activity is associated with various diseases. The study utilized 'DrugspaceX' for lead identification and repositioned FDA-approved drugs for CAMKK2 inhibition. Through virtual screening, DE273038_5 was identified as a novel candidate with potential inhibitory activity at the CAMKK2 active site.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Nicola Gambacorta, Leonardo Caputo, Laura Quintieri, Linda Monaci, Fulvio Ciriaco, Orazio Nicolotti
Summary: Three whey protein-derived peptides showed reliable binding poses within 3CL(pro), with IPAVF exhibiting the highest inhibitory activity. These peptides are introduced as promising molecules for the development of antiviral agents against SARS-CoV-2.
Article
Chemistry, Medicinal
Jingyi Yang, Xiaoyuan Lin, Na Xing, Zhao Zhang, Haiwei Zhang, Haibo Wu, Weiwei Xue
Summary: The study introduced a multiple conformation-based virtual screening strategy to discover inhibitors targeting SARS-CoV-2 M-pro, identifying potential drug candidates through ensemble docking with a protein mimetics library. Evaluation of the compounds in surface plasmon resonance and fluorescence resonance energy transfer experiments revealed their binding effectiveness and inhibitory properties against M-pro, showing promise as antiviral drug candidates for treating COVID-19.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Chemistry, Medicinal
David E. Graff, Matteo Aldeghi, Joseph A. Morrone, Kirk E. Jordan, Edward O. Pyzer-Knapp, Connor W. Coley
Summary: In this study, a technique called design space pruning (DSP) is proposed to reduce inference costs in model-guided optimization. By permanently removing poor-performing candidates from consideration, DSP achieves significant reductions in overhead costs while maintaining similar performance to baseline optimization.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Physical
Shilpa Gupta, Parbati Biswas
JOURNAL OF PHYSICAL CHEMISTRY B
(2020)
Article
Chemistry, Medicinal
Leena Aggarwal, Parbati Biswas
Summary: The hydration thermodynamics of Aβ and its FAD mutants were investigated using MD simulations and 3D-RISM theory, revealing that mutations affect hydration free energy through electrostatic and nonelectrostatic contributions, resulting in different aggregation propensities and early onset Alzheimer's disease risk.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Chemistry, Medicinal
Leena Aggarwal, Parbati Biswas
Summary: This study investigates the hydration thermodynamics of different mutants of alpha-synuclein related to familial Parkinson's disease using a computational approach. The results show that the hydration free energy and interaction volume play a crucial role in determining the aggregation kinetics of alpha-synuclein upon mutation.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Chemistry, Physical
Shivangi Sharma, Vishal Singh, Parbati Biswas
Summary: The effect of ligand binding on the conformational transitions of the add A-riboswitch in cellular environments is theoretically investigated. It was found that the transition path time for the riboswitch aptamer is longer when the ligand is bound compared to when it is unbound. Additionally, the transition path time decreases with an increase in the barrier height, which may seem counterintuitive.
JOURNAL OF CHEMICAL PHYSICS
(2021)
Article
Mechanics
Manisha Handa, Parbati Biswas
Summary: This study theoretically investigates the intramolecular relaxation dynamics of unconcatenated ring polymers in dilute solutions, finding that excluded volume interactions can decrease relaxation rates and expand the width of the relaxation spectrum.
JOURNAL OF RHEOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Vishal Singh, Parbati Biswas
Summary: The dynamics of conformational transitions of the disordered protein, amyloid-beta, were studied through simulations, revealing a two-state transition in the energy landscape. The variation of the transmission coefficient also indicated the breakdown of Kramers and Grote-Hynes theories and the emergence of dynamic disorder. These findings provide insight into the unfold-misfold transition dynamics of amyloid-beta.
Article
Mechanics
Manisha Handa, Parbati Biswas
Summary: The study investigated the influence of distance dependent excluded volume interactions (EVIs) on the conformational properties of ring polymers, showing that EVIs lead to a transition in conformation, with smaller rings being more compact and larger rings expanding. The mean square radius of gyration and fractal dimension of the rings are affected by EVI, with this effect being more pronounced for larger rings.
JOURNAL OF RHEOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Prakash Jha, Prithvi Singh, Shweta Arora, Armiya Sultan, Arnab Nayek, Kalaiarasan Ponnusamy, Mansoor Ali Syed, Ravins Dohare, Madhu Chopra
Summary: This study investigates the gene expression profile of SARS-CoV-2 patients and identifies potential therapeutic targets for COVID-19 using chemogenomics strategy and molecular docking. The ARHGEF1 gene is identified as a probable target for therapy, but further validation is needed.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Prakash Jha, Daman Saluja, Madhu Chopra
Summary: A structure-based pharmacophore model was developed for the Nsp15 endonuclease, and virtual screening of databases was performed using this model. After validation through molecular docking, molecular dynamics simulations, and binding free energy calculations, repurposed drugs were discovered as potential inhibitors for the Nsp15 enzyme of SARS-CoV-2, providing a basis for immediate drug development.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Polymer Science
Manisha Handa, Parbati Biswas
Summary: This study investigates the relaxation dynamics of ring polymers in dilute solutions with both repulsive excluded volume interactions and attractive interactions using Rouse-Zimm theory. The results show that the overall motion dominates the relaxation of ring polymers with repulsive interactions, while the opposite is true for ring polymers with attractive interactions. The spin-lattice relaxation rate exhibits a characteristic maximum at different frequencies.
Article
Chemistry, Multidisciplinary
Priya Dey, Parbati Biswas
Summary: The hydration thermodynamics of various protein structures, including globular protein, intrinsically disordered protein regions, and fully disordered protein, was studied using molecular dynamics simulations and 3D-RISM theory. The hydration free energy was found to decrease with an increase in percentage disorder, indicating favorable interactions between disordered proteins and solvent. The contribution of electrostatic interactions and percentage disorder to the aggregation propensity of proteins was confirmed. Residue-wise decomposition analysis showed that disordered regions play a bigger role in hydration free energy. The dominant contribution of electrostatic interactions was observed, with negatively charged residues contributing more to proteins with negative net charge and positively charged residues contributing more to proteins with positive net charge.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Sumit Kumar, Parbati Biswas
Summary: Ring polymers differ significantly from linear polymers in terms of their properties such as intrinsic viscosity, complex viscosity, and dielectric relaxation. Excluded volume interactions and hydrodynamic interactions play important roles in ring polymers. In addition, the size of the ring and the interactions between rings also have an impact on the properties of ring polymers.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Chemistry, Physical
Shivangi Sharma, Vishal Singh, Parbati Biswas
Summary: In this study, the conformational transitions of the adenosine deaminase Ariboswitch aptamer were investigated using steered molecular dynamics (SMD) simulations and the generalized Langevin equation. The results showed that the unfold-fold transitions are faster and more probable than the fold-unfold transitions, and the transition path time is insensitive to the exact mechanism of the transition events. The complexity of the cellular environment increases the mean first passage time.
ACS PHYSICAL CHEMISTRY AU
(2022)
Meeting Abstract
Infectious Diseases
Prakash Jha, Madhu Chopra
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2021)
Meeting Abstract
Infectious Diseases
Ravi Kant, Prakash Jha, Madhu Chopra, Daman Saluja
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2021)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)