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
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
Chemistry, Medicinal
Rajdeep Ray, Gautham G. Shenoy, T. N. V. Ganesh Kumar
Summary: This study developed and compared two QSAR models based on triazole molecules with antitubercular activity, with the CoMSIA model showing significantly better results than the CoMFA model in terms of predicting the structural importance of these compounds. The CoMSIA contours provided insights into the role of various atoms and groups in the biological activity of the triazole molecules.
CURRENT COMPUTER-AIDED DRUG DESIGN
(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, Multidisciplinary
Yassine Koubi, Youness Moukhliss, Halima Hajji, Marwa Alaqarbeh, Mohammed Aziz Ajana, Hamid Maghat, Tahar Lakhlifi, Mohammed Bouachrine
Summary: In this study, 3D-QSAR, molecular docking, ADMET, and molecular dynamics were used to investigate the inhibitory activity of 1,2,3-triazole derivatives against Mycobacterium tuberculosis. The 3D-QSAR study revealed CoMFA and CoMSIA models with good predictability. Molecular docking confirmed the interaction between Gln164 and Lys160 residues at the H37Rv active site. Furthermore, the ADMET properties and drug similarity of the new inhibitors were analyzed. These findings can aid in the development of new therapeutic candidates against multidrug-resistant tuberculosis.
NEW JOURNAL OF CHEMISTRY
(2023)
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
Biochemical Research Methods
Chayanin Hanwarinroj, Paptawan Thongdee, Darunee Sukchit, Somjintana Taveepanich, Pharit Kamsri, Auradee Punkvang, Sombat Ketrat, Patchreenart Saparpakorn, Supa Hannongbua, Khomson Suttisintong, Prasat Kittakoop, James Spencer, Adrian J. Mulholland, Pornpan Pungpo
Summary: This study used quantitative structure-activity relationship methods to investigate the inhibitory effects of quinazoline derivatives on PknB. Molecular dynamics simulations and binding energy calculations revealed that the quinazoline core and overall hydrophobicity were major contributors to the affinity of PknB. Additional quinazoline derivatives were designed and evaluated, and predictive models identified sixteen compounds with superior PknB binding and other desirable properties.
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2022)
Article
Chemistry, Organic
Khushal Kapadiya, Yashwantsinh Jadeja, Ranjan Khunt
JOURNAL OF HETEROCYCLIC CHEMISTRY
(2018)
Article
Chemistry, Medicinal
Khushal M. Kapadiya, Ranjan C. Khunt
LETTERS IN DRUG DESIGN & DISCOVERY
(2019)
Article
Chemistry, Medicinal
Maheshkumar R. Borkar, Santosh Nandan, Harish K. M. Nagaraj, Jayashree Puttur, Jisha Manniyodath, Dipankar Chatterji, Evans C. Coutinho
MEDICINAL CHEMISTRY
(2019)
Article
Acoustics
Ritu Bala, Jagriti Behal, Nikesh A. Shah, K. N. Rathod, Vinit Prakash, Ranjan C. Khunt
ULTRASONICS SONOCHEMISTRY
(2018)
Article
Chemistry, Multidisciplinary
Jagriti Behal, Varinder Kaur, Jakub Mrzyglod, Marcin Hoffmann, Agnieszka Janiak, Karanjeet Kaur, Ranjan Khunt
Article
Biochemistry & Molecular Biology
Faiza Hanif Waghu, Ulka Gawde, Anish Gomatam, Evans Coutinho, Susan Idicula-Thomas
CHEMICAL BIOLOGY & DRUG DESIGN
(2020)
Article
Chemistry, Medicinal
Joginder Singh Paneysar, Stephen Barton, Premlata Ambre, Evans Coutinho
Summary: This paper reports the antibacterial activity and biocompatibility of a temperature responsive topical film containing silver nanoparticles. The film is fabricated from pullulan-g-pNIPAM and can release silver nanoparticles over a period of 48 hours. The film exhibits good swelling properties, antibacterial activity against gram-positive and gram-negative bacteria, and is biocompatible with HeK293 cells. It is a new therapeutic device for non-healing wounds.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Biochemical Research Methods
Maheshkumar R. Borkar, Evans C. Coutinho
Summary: Peptide therapeutics play a prominent role in medical practice, but optimizing a peptide library is time-consuming and expensive. This study demonstrates the successful prediction of peptide retention time using Comparative Protein Modeling-Quantitative Structure Retention Relationship (ComProM-QSRR) method.
JOURNAL OF CHROMATOGRAPHY A
(2022)
Review
Pharmacology & Pharmacy
Chandan Gupta, Isha Naik, Mala Menon, Premlata Ambre, Evans Coutinho
Summary: Polymeric drug conjugates (PDCs) have been extensively researched as a drug delivery system for cancer therapy. Successful PDC conjugates have shown sustained drug release with reduced toxicity and improved tumor retention effect. The selection of over-expressed receptors and ligands plays a vital role in designing targeted PDCs that can distinguish between healthy and tumor cells. Despite controversies, continuous efforts are being made to develop active targeted PDC delivery systems for revolutionizing cancer treatment.
CURRENT DRUG DELIVERY
(2023)
Article
Chemistry, Organic
Navneet P. Mori, Priti K. Parmar, Vijay M. Khedkar, Ranjan C. Khunt
Summary: The novel series of phthalimide-1H-1,2,3-triazole derivatives synthesized in this study showed potent anticancer activity against leukemia, non-small cell lung cancer, renal cancer, and melanoma cancer cell lines. The compounds were comprehensively characterized and their antimicrobial activity was also tested. Molecular docking studies provided insights into the mechanism of action.
POLYCYCLIC AROMATIC COMPOUNDS
(2023)
Article
Biochemistry & Molecular Biology
Anish Gomatam, Blessy Joseph, Poonam Advani, Mushtaque Shaikh, Krishna Iyer, Evans Coutinho
Summary: Optimizing the pharmacokinetics of drug candidates is a challenge in drug development. The use of quantitative structure-pharmacokinetic relationship (QSPKR) as an in silico tool has emerged as an alternative to experimental testing. However, developing QSPKR models that can be used in real-world pre-screening situations remains challenging due to the complexity of drug disposition processes.
MOLECULAR DIVERSITY
(2023)
Review
Biochemistry & Molecular Biology
Savita Tauro, Bharat Dhokchawle, Popat Mohite, Deepali Nahar, Sahaya Nadar, Evans Coutinho
Summary: Cancer is a major health problem and current treatments often have severe toxic effects. Plant-based drugs have shown potential for cancer treatment, with natural compounds like curcumin and resveratrol being extensively researched. Several plants, including Athyrium hohenackerianum and Panax ginseng, have shown anticancer activity and could be potential clinical candidates.
CURRENT MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Chandan Gupta, Pinky Singh, Shashikant Vaidya, Premlata Ambre, Evans Coutinho
Summary: The major challenges in current cancer chemotherapy, including drug resistance, low efficacy, and non-selectivity, can lead to undesirable side effects. This study presents a solution to these challenges through a dual targeting approach for tumors that overexpress CD44 receptors. A nanoformulation called tHAC-MTX nano assembly, composed of hyaluronic acid (HA) conjugated with methotrexate (MTX) and complexed with a thermoresponsive polymer 6-O-carboxymethylchitosan (6-OCMC) graft poly(N-isopropylacrylamide) [6-OCMC-g-PNIPAAm], was developed. The nano assembly exhibited faster drug release at higher temperatures of tumor tissues and enhanced drug release in the presence of hyaluronidase enzyme. The nanoparticles also showed higher cellular uptake and cytotoxicity in cancer cells that overexpress CD44 receptors, suggesting a receptor binding and cellular uptake mechanism. Such multi-targeting nano-assemblies have the potential to improve the efficacy and reduce the side effects of cancer chemotherapy.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Multidisciplinary Sciences
Joginder Singh Paneysar, Sumeet Jain, Nida Ahmed, Stephen Barton, Premlata Ambre, Evans Coutinho
SN APPLIED SCIENCES
(2020)
Article
Water Resources
Joginder Singh Paneysar, Snehal Sawant, Meng Hei Ip, Sukhwinder Kaur Bhullar, Stephen Barton, Premlata Ambre, Evans Coutinho
WATER PRACTICE AND TECHNOLOGY
(2019)
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)