Article
Biochemistry & Molecular Biology
Amina Goudzal, Abdellah El Aissouq, Hicham El Hamdani, El Ghalia Hadaji, Abdelkrim Ouammou, Mohammed Bouachrine
Summary: In this study, a 3D-QSAR analysis was performed on a series of 2, 4, 5-trisubstituted imidazole derivatives to design potent kinase II alpha subunit (CK2) inhibitors. The COMFA and COMSIA models showed excellent performance with high Q(2) and R-2 values. The validity of the models was confirmed through various validation tests. The study's findings provide useful theoretical references for future experimental studies.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Agata Zieba, Tuomo Laitinen, Jayendra Z. Patel, Antti Poso, Agnieszka A. Kaczor
Summary: The study successfully constructed 3D-QSAR CoMFA and CoMSIA models for a series of 31 FAAH inhibitors with 1,3,4-oxadiazol-2-one moiety, which showed good statistical parameters and were validated using various techniques. The field contributions in the CoMFA and CoMSIA models varied, influencing the ligand-enzyme interactions in different ways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Swapnil P. Bhujbal, Jung-Mi Hah
Summary: Radiotherapy and chemotherapy are standard cancer treatments used in combination with surgery for around 60% of cancer patients. Only a few patients respond to immune checkpoint blockage due to low tumor immunogenicity, with tumor cells often evading immune surveillance through CD73 signaling and extracellular adenosine production. In this study, non-nucleotide small molecule inhibitors targeting CD73 were designed using molecular docking and 3D-QSAR studies, showing promising activity compared to existing compounds. Further experimental validation of these new inhibitors is required.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Jin-Hee Kim, Jin-Hyun Jeong
Summary: In this study, a series of thieno-pyrimidine derivatives were analyzed using three-dimensional quantitative structure-activity relationship (3D-QSAR) to identify key structural features for inhibitory biological activities. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models were established, showing reliable and robust performance. The predictive capabilities of these models were confirmed through external validation and progressive scrambling stability test. This research provides valuable information for the further optimization and design of novel inhibitors against metastatic breast cancer.
Article
Biochemistry & Molecular Biology
Saida Khamouli, Salah Belaidi, Mebarka Ouassaf, Touhami Lanez, Said Belaaouad, Samir Chtita
Summary: The study performed a three-dimensional quantitative structure-activity relationships (3D-QSAR) analysis on 26 azaindazole derivatives as LRRK2 inhibitors, achieving high activity-descriptor relationship efficiency. The models were validated externally and through docking studies, confirming their reliability and providing valuable clues for designing new compounds against LRRK2. Furthermore, an analysis of the compounds' ADMET properties and drug likeness was conducted, aiding in the optimization of new anti-Parkinson drugs.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Physical
Xiao Ding, Dongwei Kang, Lin Sun, Peng Zhan, Xinyong Liu
Summary: With the increasing number of AIDS patients, the search for new potent anti-HIV drugs becomes urgent. Through the analysis of CoMFA, CoMSIA, and 2D-QSAR models, insights into the design of novel anti-HIV agents can be obtained.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Toxicology
Yajuan Bi, Xue Wang, Huixiang Li, Yiqing Tian, Lifeng Han, Chunshan Gui, Youcai Zhang
Summary: Flavonoids, widely found in vegetables, fruits, grains, and herbs, exhibit inhibitory effects on the organic cation transporter 2 (OCT2) which plays a crucial role in drug-drug interactions. This study investigated the inhibitory effect of 28 flavonoids on OCT2 and revealed the structural features that affect their interaction. The findings provide valuable insights into the interactions and prediction of flavonoids with OCT2.
TOXICOLOGY LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Yunmei Liu, Zejie Tian, Hui Li, Zhenhua Liu, Lei Shi, Lingyan Yang
Summary: In this study, 3D-QSAR models were constructed to investigate the structure-activity relationship of chrysin. The structures of 54 chrysin derivatives were constructed using SYBYL-X 2.0 software, and the models were built using CoMFA and CoMSIA methods. The results showed that certain groups attached to the 7-O-alkane chain of chrysin, such as amino acids, enhance its activity, while excessively long chains or bulky hydrophobic groups reduce the activity. On the other hand, the introduction of bulky hydrophobic groups on the side chains of amino acids increases the activity of the molecule.
JOURNAL OF MATHEMATICAL CHEMISTRY
(2023)
Article
Food Science & Technology
Yijie Yang, Qi Tian, Shiming Li, Bo Li
Summary: In this study, 3D-QSAR analysis was performed to investigate the structure-activity relationship of collagen hydrolysate peptides. The results showed that Hyp, rather than Pro, had a greater impact on improving antiplatelet activity. The predicted peptide EOGE exhibited antiplatelet activity and inhibited thrombus formation.
Article
Biochemistry & Molecular Biology
Bhumi M. Shah, Sneha R. Sagar, Priti Trivedi
Summary: Researchers have identified DPP IV as a target for diabetes treatment, and 3D QSAR studies have helped to determine important structural features of triazole derivatives, leading to the design of novel compounds that may serve as promising DPP IV inhibitors for the treatment of diabetes.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Medicinal
Merugumala Kusuma, Sahil Arora, Sourav Kalra, Anuhar Chaturvedi, Michael Heuser, Raj Kumar
Summary: In this study, novel anti-tumour agents were designed using computational methods focusing on the shikonin scaffold for better activity. Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) were used to rationalize the correlation between structural features and PKM2 inhibitory activity. These predictive computational models will aid in the design and synthesis of potent PKM2 inhibitors at a low cost.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
V. K. Vyas, S. Bhati, M. Sharma, P. Gehlot, N. Patel, S. Dalai
Summary: 2,4-Disubstituted quinoline derivatives were designed, synthesized, and evaluated for antimalarial activity based on a 3D-QSAR study. CoMFA and CoMSIA models were used on a dataset of 178 quinoline derivatives, and PLS analysis validated the results. 10 derivatives were synthesized and screened, with compounds #5 and #19 showing maximum reductions of 64% and 57% in parasitaemia level, respectively.
SAR AND QSAR IN ENVIRONMENTAL RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Yuwei Wang, Yifan Guo, Shaojia Qiang, Ruyi Jin, Zhi Li, Yuping Tang, Elaine Lai Han Leung, Hui Guo, Xiaojun Yao
Summary: In this study, the structure-activity relationships and binding modes of a series of anthraquinone derivatives targeting PGAM1 were investigated using 3D-QSAR, molecular docking, and molecular dynamics simulations, which showed satisfactory predictive ability. Molecular dynamics simulations revealed key residues and dominant interactions, as well as stable hydrogen bond formations during the ligand binding process. Overall, the study provided theoretical guidance for the design of new anthraquinone derivatives as PGAM1 inhibitors.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Etibaria Belghalia, Mohamed Ouabane, Salma El Bahi, Hafiz Muzzammel Rehman, Abdelouahid Sbai, Tahar Lakhlifi, Mohammed Bouachrine
Summary: Acute myeloid leukemia, a serious condition affecting stem cells, can be treated using BRD4 inhibitors that suppress cell proliferation. Through molecular modeling techniques and simulation, this study revealed the structural elements and interaction mode of effective BRD4 inhibitors. The incorporation of bulky substituents on the pyridinone ring and hydrophobic/electrostatic substituents on the methoxy-substituted phenyl ring enhanced interactions with the BRD4 target, leading to improved oral bioavailability and non-toxic properties.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Medicinal
Yuan Zhang, Juan Liu, Xin Wu, Suming Yang, Yao Li, Songbin Liu, Saifei Zhu, Xuan Cao, Zhizhong Xie, Xiaoyong Lei, Honglin Huang, Junmei Peng
Summary: The anti-chronic myeloid leukemia activity of thiazole aminobenzamide derivatives was tested in vitro using a viability assay method and was found to exhibit good inhibitory activities. Analysis using CoMFA and CoMSIA showed a relationship between the structure of these derivatives and their inhibition of leukemia cell activity, with specific substitutions improving the anti-CML activity.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
