Article
Biochemistry & Molecular Biology
Cem Yamali, Halise Inci Gul, Mehtap Tugrak Sakarya, Begum Nurpelin Saglik, Abdulilah Ece, Goksun Demirel, Merve Nenni, Serkan Levent, Ahmet Cihat Oner
Summary: This study synthesized a series of 4-((2-(aryl)-4-oxoquinazolin-3(4H)-yl)amino) benzenesulfonamides and investigated their inhibition potentials against MAOs. The most potent compounds 7 and 8 showed high selectivity and reversibility towards MAO-A, suggesting their potential as therapeutic agents for neurodegenerative diseases.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Daniel Chavarria, Ophelie Da Silva, Sofia Benfeito, Sandra Barreiro, Jorge Garrido, Fernando Cagide, Pedro Soares, Fernando Remiao, Xavier Brazzolotto, Florian Nachon, Paulo J. Oliveira, Jose Dias, Fernanda Borges
Summary: The study investigates the effects of compounds 2-5 on neurodegeneration, showing their antioxidant properties and regulation of neurotransmitter-metabolizing enzymes. Compound 4 stands out for its superior bioactivity and safety in addressing both mitochondrial oxidative stress and neurotransmitter depletion.
Article
Chemistry, Medicinal
Maria J. Matos, Paula Novo, Lucia Mayan, Iria Torres, Eugenio Uriarte, Matilde Yanez, Jose Angel Fontenla, Francesco Ortuso, Stefano Alcaro, Francesca Procopio, Maria Isabel Rodriguez-Franco, Cristina Val, Maria I. Loza, Jose Brea, Fernanda Borges, Dolores Vina
Summary: Psychiatric and neurological disorders affect millions of people worldwide, and current treatments are limited in their effectiveness. New therapeutic solutions are urgently needed to improve the lives of patients.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Giovanna L. Delogu, Amit Kumar, Gianluca Gatto, Fernando Bustelo, Lucia M. Saavedra, Maria Isabel Rodriguez-Franco, Reyes Laguna, Dolores Vina
Summary: A new series of 2-phenylbenzofuran derivatives were designed and synthesized to investigate their MAO inhibitory activity and selectivity. The presence of methoxy substituents in the 2-phenyl ring and nitro groups at positions 5 or 7 on the benzofuran moiety affected the affinity for MAO-A or MAO-B. Experimental results showed 2-(3-methoxyphenyl)-5-nitrobenzofuran 9 as the most potent MAO-B inhibitor and 7-nitro-2-phenylbenzofuran 7 as the most potent MAO-A inhibitor in this series, with methoxy groups on the 2-phenyl ring playing a key role in inhibitory activity.
BIOORGANIC CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Vishal Payyalot Koyiparambath, Jong Min Oh, Ahmed Khames, Mohamed A. Abdelgawad, Aathira Sujathan Nair, Lekshmi R. Nath, Nicola Gambacorta, Fulvio Ciriaco, Orazio Nicolotti, Hoon Kim, Bijo Mathew
Summary: Six halogenated trimethoxy chalcone derivatives were synthesized and evaluated for their inhibitory potential against MAOs and BACE-1. Compounds CH4 and CH5 showed strong inhibition of MAO-B, exhibited protective effects on VERO cells, and had high blood brain barrier permeabilities.
Review
Chemistry, Medicinal
Ashwani Kumar, Meenakshi Bhatia, Archana Kapoor, Parvin Kumar, Sunil Kumar, Sunil Kumar
Summary: Monoamine oxidase enzyme plays an essential role in brain function regulation, with its inhibitors showing potential in the treatment of neurological disorders. Reversible MAO inhibitors, which have been recently studied, may serve as safer alternatives to old monoamine oxidase inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Stefania Olla, Chiara Siguri, Antonella Fais, Benedetta Era, Massimo Claudio Fantini, Amalia Di Petrillo
Summary: This study investigates the mechanisms underlying the antioxidant properties of quercetin and its ability to target endogenous oxidant enzymes. The results demonstrate that quercetin acts as a free radical scavenger by donating electrons and effectively inhibits the activity of various oxidative enzymes by binding to them with high affinity. Molecular docking and subsequent molecular dynamics confirm the binding of quercetin to these enzymes, with different stability phases observed depending on the enzyme bound. The findings suggest that quercetin has potential as a natural therapy for diseases related to oxidative stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Physical
Milad Nouraliei, Hamedreza Javadian, Khourshid Mehdizadeh, Nazanin Sheibanian, Abdollatif Shafaei Douk, Fatemeh Mohammadzadeh, Noushin Osouleddini
Summary: This study used molecular docking technique to investigate the interactions between phenelzine and its derivatives with monoamine oxidase, and explored the feasibility of carbon nanostructures as drug carriers. The results showed that nanostructures could serve as carriers for phenelzine derivatives and potentially be used as new drugs to inhibit monoamine oxidase.
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
(2023)
Article
Biochemistry & Molecular Biology
Mehmet Abdullah Alagoz, Jong Min Oh, Yaren Nur Zenni, Zeynep Ozdemir, Mohamed A. Abdelgawad, Ibrahim A. Naguib, Mohammed M. Ghoneim, Nicola Gambacorta, Orazio Nicolotti, Hoon Kim, Bijo Mathew
Summary: The study synthesized and evaluated 16 compounds, finding that TR2 and TR16 showed potent and highly selective inhibition against MAO-B, making them promising for managing multiple neurodegenerative diseases.
Article
Chemistry, Medicinal
Zelin Yang, Xin Huang, Wenfang Lai, Yuheng Tang, Junjie Liu, Yingzheng Wang, Kedan Chu, John Brown, Guizhu Hong
Summary: Twenty-six novel derivatives of salidroside were synthesized, with pOBz identified as a more cytoprotective derivative compared to salidroside. pOBz competitively and selectively inhibited MAO-B enzyme activity, showing potent neuroprotective properties in a rat model of cerebral ischemia-reperfusion injury.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Rabia Basri, Shamool Fatima, Saquib Jalil, Aqeel Imran, Noor Fatima, Asad Syed, Ali H. Bahkali, Jamshed Iqbal, Zahid Shafiq
Summary: This study reports the design, synthesis, and evaluation of 2-oxoquinoline-based thiosemicarbazones as multipotent analogs for the treatment of Alzheimer's disease. The compounds demonstrated potent inhibition of both cholinesterase and monoamine oxidase enzymes. The kinetic and molecular docking studies provided insights into the mode of inhibition and interaction with the enzymes.
ARCHIV DER PHARMAZIE
(2023)
Article
Environmental Sciences
Qiao Xue, Xian Liu, Paul Russell, Jin Li, Wenxiao Pan, Jianjie Fu, Aiqian Zhang
Summary: Molecular docking is a widely used method to predict the binding modes of small-molecule ligands to the target binding site. In this study, the performance of three popular docking programs, Autodock, Autodock Vina, and Surflex-Dock, was systematically compared for a series of structurally similar flavonoids binding to the estrogen receptor alpha (ER alpha). The results showed that Surflex-Dock exhibited higher accuracy than Autodock and Autodock Vina. The hydrogen bond overweighting by Autodock and Autodock Vina led to incorrect binding results, while Surflex-Dock effectively balanced both hydrogen bond and hydrophobic interactions. The selection of initial receptor structure was also found to be critical for the docking conformation. Moreover, key residues in ER alpha-flavonoids complexes were identified.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2022)
Article
Chemistry, Physical
Yuejiang Yu, Chun Cai, Jiayue Wang, Zonghua Bo, Zhengdan Zhu, Hang Zheng
Summary: Uni-Dock is a GPU-accelerated molecular docking program that supports various scoring functions and excels in speed and efficiency compared to other GPU-accelerated programs. It achieves significant speedup by optimizing data flow and implementing parallel processing, outperforming previous docking programs like AutoDock Vina. Uni-Dock has demonstrated improved performance in docking experiments, and it has been proven to be the fastest GPU-accelerated docking program to date, especially in screening ultralarge molecular libraries.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Biochemistry & Molecular Biology
Shivananda Kandagalla, Maria Grishina, Jurica Novak, Hrvoje Rimac, B. S. Sharath, Vladimir Potemkin
Summary: Molecular docking is a popular and widely used method for identifying novel molecules against a target of interest. This study evaluates a quantum free-orbital AlteQ method for evaluating docking complexes. The AlteQ method calculates the electron density using Slater's type atomic contributions and assesses the interactions between the receptor and the ligand based on the overlap of electron clouds. Three different equations were used to determine the quality of interactions in experimental complexes and docked complexes obtained using AutoDock Vina and AutoDock 4.2.6.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Virology
Yujie Sun, Wen Liu, Bing Luo
Summary: This review summarizes current research on how viral infections participate in the occurrence and development of human diseases through MAO. The viruses discussed in this review include hepatitis C virus, dengue virus, severe acute respiratory syndrome coronavirus 2, human immunodeficiency virus, Japanese encephalitis virus, Epstein-Barr virus, and human papillomavirus. The effects of MAO inhibitors such as phenelzine, clorgyline, selegiline, M-30, and isatin on viral infectious diseases are also described in this review. This information will provide new insights into the treatment and diagnosis of these viral diseases.
REVIEWS IN MEDICAL VIROLOGY
(2023)
Article
Genetics & Heredity
Rameen Shakur, Juan Pablo Ochoa, Alan J. Robinson, Abhishek Niroula, Aneesh Chandran, Taufiq Rahman, Mauno Vihinen, Lorenzo Monserrat
Summary: This study investigated the impact of troponin T variations on the thin filament complex using an unbiased systems biology method, and integrated clinical data to identify specific regions associated with cardiovascular risks. The findings suggest that variations in certain regions are linked to different outcomes, such as sudden cardiac death or heart failure, highlighting the importance of genotype-clinical data integration for risk stratification in patients with familial cardiomyopathy.
NPJ GENOMIC MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Ghita Ghislat, Taufiq Rahman, Pedro J. Ballester
Summary: With the availability of more bioactivity and protein structure data, scoring functions using machine learning are becoming more accurate and widely applicable. Improvements in selecting suitable decoys and training and evaluating ML-based scoring functions have enhanced their performance for virtual screening. Recent applications have shown promising results, indicating potential for future advancements in structure-based virtual screening studies.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Christopher Heng Xuan Ha, Nung Kion Lee, Taufiq Rahman, Siaw San Hwang, Wai Keat Yam, Xavier Wezen Chee
Summary: This study demonstrates the use of regression QSAR modeling to predict the activity of INSTIs and applies the models to drug repositioning. The top-ranked compounds are further evaluated for their target engagement activity using molecular docking and accelerated Molecular Dynamics simulation, and their potential as INSTIs is assessed through literature search.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Multidisciplinary Sciences
Zhu-Hong Li, Thayer P. King, Lawrence Ayong, Beejan Asady, Xinjiang Cai, Taufiq Rahman, Stephen A. Vella, Isabelle Coppens, Sandip Patel, Silvia N. J. Moreno
Summary: This study characterizes a TPC from Toxoplasma gondii that localizes to the apicoplast, playing a critical role in maintaining its integrity and facilitating Ca2+ uptake from the ER through stabilizing inter-organelle contact.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Yasin Gokce, Orhan Erkan, Kamil Savas, Taufiq Rahman, Nazmi Yaras
Summary: This study investigated the role of store-operated calcium entry (SOCE) in calcium handling in diabetic rat cardiomyocytes and found that SOCE function was reduced while Orai1 and Orai3 protein expression was upregulated in diabetes. Losartan treatment did not affect the protein expression pattern. The imbalance between SOCE function and protein expression levels may be due to impaired interaction between Stim and Orai proteins.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Cell Biology
Sandip Patel, Yu Yuan, Gihan S. Gunaratne, Taufiq Rahman, Jonathan S. Marchant
Summary: Two-pore channels (TPCs) are ancient members of the voltage-gated ion channel superfamily that are primarily found on acidic organelles. TPCs can be activated by ligands and have calcium and sodium permeability, with the ability to switch their ion selectivity in response to specific agonists.
Article
Chemistry, Medicinal
Xavier Chee Wezen, Aneesh Chandran, Rohan Sakariah Eapen, Elaine Waters, Laura Bricio-Moreno, Tommaso Tosi, Stephen Dolan, Charlotte Millership, Aras Kadioglu, Angelika Grundling, Laura S. Itzhaki, Martin Welch, Taufiq Rahman
Summary: This study used molecular docking and molecular dynamics simulations to model the binding mode of compound 1771 to LtaS. The model was validated and lead optimization resulted in an improved compound 4 with enhanced affinity for LtaS. Compound 4 reduced LTA production, induced aberrant morphology, and decreased bacteria titers in mice infected with S. aureus. Analysis of simulation trajectories revealed a possible transient cryptic pocket, and virtual screening led to the discovery of new inhibitors that potentiate beta-lactams against methicillin-resistant S. aureus.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Cell Biology
Luc R. A. Francis, Sarah L. Millington-Burgess, Taufiq Rahman, Matthew T. Harper
Summary: Thrombin activates platelets through PAR1 and PAR4, with PAR1 being the more rapidly activated receptor. Q94, an allosteric modulator of PAR1, has been reported to inhibit PAR1-G alpha q coupling in various cell lines, but its effects on human platelet activation have not been studied. Our data suggest that Q94 may have off-target effects in platelets independent of PAR1, precluding its use as a selective PAR1 allosteric modulator.
Editorial Material
Cell Biology
Taufiq Rahman, Sandip Patel
Summary: TRPML1 is an endolysosomally-expressed cation channel, activated by PI(3,5)P-2 and synthetic agonists like rapamycin. New high resolution cryo-EM structures of TRPML1 bound to both PI(3,5)P-2 and temsirolimus reveal molecular insights into how the channel integrates two agonists at distal sites but cooperatively.
Article
Biochemistry & Molecular Biology
Juliyan Gunasinghe, Siaw San Hwang, Wai Keat Yam, Taufiq Rahman, Xavier Chee Wezen
Summary: In this study, a QSAR model was developed to predict potential inhibitors for the high-risk human papillomavirus E1 protein, and the Drugbank database was screened using the model. Three compounds were identified as candidate scaffolds for the future design of E1 inhibitors based on molecular docking and dynamics simulations.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Cell Biology
Alaa Droubi, Connor Wallis, Karen E. Anderson, Saifur Rahman, Aloka de Sa, Taufiq Rahman, Len R. Stephens, Philip T. Hawkins, Martin Lowe
Summary: This study identifies the inositol 5-phosphatase INPP5B as a key regulator of actin remodeling, BCR clustering, and downstream signaling in antigen-stimulated B cells. INPP5B acts by dephosphorylating PI(4,5)P-2, which is necessary for actin disassembly, BCR mobilization, and cell spreading. INPP5B may represent a potential target for the treatment of B cell malignancies caused by aberrant BCR signaling.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Yu Yuan, Dawid Jaslan, Taufiq Rahman, Stephen R. Bolsover, Vikas Arige, Larry E. Wagner, Carla Abrahamian, Rachel Tang, Marco Keller, Jonas Hartmann, Anna S. Rosato, Eva-Maria Weiden, Franz Bracher, David Yule, Christian Grimm, Sandip Patel
Summary: This study reveals that TPC2 can selectively increase its permeability to calcium ions when co-activated by the endogenous ligands NAADP and PI(3,5)P-2. This finding indicates that the flux of different ions through the same channel can be independently controlled and identifies TPC2 as a potential coincidence detector that optimizes lysosomal calcium signaling.
NATURE COMMUNICATIONS
(2022)
Review
Cell Biology
Sandip Patel, Yu Yuan, Cheng-Chang Chen, Dawid Jaslan, Gihan Gunaratne, Christian Grimm, Taufiq Rahman, Jonathan S. Marchant
Summary: This review discusses the electrophysiology of two-pore channels TPC1 and TPC2, including their gating by Ca2+-mobilizing messenger NAADP and/or the lipid PI(3,5)P-2, regulation by H+, Ca2+, and Mg2+, and impact of single-nucleotide polymorphisms. The article also explores the effect of various substances on channel activity, as well as the rerouting of channels to the cell surface for easier recording.
Meeting Abstract
Pharmacology & Pharmacy
Roxanna Hajbabaie, Matthew Harper, Taufiq Rahman
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Meeting Abstract
Pharmacology & Pharmacy
Anna Suchankova, Kathleen Bowman, Matthew Harris, Taufiq Rahman, Graham Ladds
BRITISH JOURNAL OF PHARMACOLOGY
(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)
