Article
Engineering, Environmental
Giovanna J. Lavado, Diego Baderna, Edoardo Carnesecchi, Alla P. Toropova, Andrey A. Toropov, Jean Lou C. M. Dorne, Emilio Benfenati
Summary: Soil pollution is a critical environmental challenge that can have adverse effects on both humans and the ecosystem. Various bioassays have been developed to investigate the soil ecotoxicity of chemicals, including a 28-day collembolan reproduction test with the springtail Folsomia candida. Despite limited toxicity data for Collembola, QSAR models have been developed for predicting reproductive toxicity induced by organic compounds in Folsomia candida, showing good predictive performance for ecological risk assessment of chemicals.
JOURNAL OF HAZARDOUS MATERIALS
(2022)
Article
Chemistry, Medicinal
Liqiang Meng, Yanhong Ou-Yang, Fuyin Lv, Jiarong Song, Jianxin Yao
Summary: This study employed CoMFA and CoMSIA methods to investigate APN small molecule inhibitors. The reliable and predictive models obtained provide useful structural insights for improving the activity of designed APN small molecule inhibitors.
LETTERS IN DRUG DESIGN & DISCOVERY
(2022)
Article
Chemistry, Physical
Laise P. A. Chiari, Aldineia P. da Silva, Aline A. de Oliveira, Celio F. Lipinski, Kathia M. Honorio, Alberico B. F. da Silva
Summary: Neuropathic pain is a difficult-to-treat syndrome that significantly impacts patients' quality of life, with current drugs showing limitations. Research suggests the sigma-1 receptor as a promising target for treatment. Using QSAR techniques, new sigma-1R antagonists with significant biological affinity values were successfully designed and validated.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Article
Engineering, Environmental
Mainak Chatterjee, Kunal Roy
Summary: This paper developed QSAR models for predicting aquatic toxicity, using Partial Least Squares regression as a statistical tool. The models were based on structural features of individual chemicals and mixture components, with quality assessed by strict validation parameters. The final models are robust, highly predictive, and mechanistically interpretable for predicting toxicity of untested chemical mixtures within the domain of applicability.
JOURNAL OF HAZARDOUS MATERIALS
(2021)
Article
Biochemistry & Molecular Biology
Sowmya Andole, Gouthami Thumma, Rajasekhar Reddy Alavala, Kiran Gangarapu
Summary: The present work aimed to develop a Field-based 3D-QSAR model using existing JAK-2 inhibitors. The JAK-STAT pathway is known to be involved in autoimmune diseases and myeloproliferative diseases. A Field-based 3D QSAR model was developed to determine the inhibitory potential of ligands. Virtual screening and molecular docking were performed to validate the results. The study showed the potential for discovering new JAK-2 inhibitors using the developed 3D QSAR model.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Multidisciplinary
Mouad Lahyaoui, Hafsa El-Idrissi, Taoufiq Saffaj, Bouchaib Ihssane, Nabil Saffaj, Rachid Mamouni, Youssef Kandri Rodi
Summary: In this study, 28 compounds derived from phosphorus-substituted quinoline were investigated for their anti-proliferative activity and binding affinity with proteins related to lung, ovarian, and kidney malignancies. The results suggest that these compounds could be valuable models for the development of more effective anticancer prospects.
ARABIAN JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Kabiruddin Khan, Kunal Roy
Summary: Organic chemicals (OCs) are a significant output of chemical and allied industries and their detection in aquatic compartments has raised ecological concerns. In this study, in silico techniques were employed to develop interspecies models for ecotoxicity prediction using data from the ECOTOX database. The results show that SSD-derived models offer more reliable predictions compared to other in silico techniques.
Article
Biochemistry & Molecular Biology
Laise P. A. Chiari, Aldineia P. da Silva, Kathia M. Honorio, Alberico B. F. da Silva
Summary: This study used quantum and chemometric methods to investigate the relationship between the structure and psychoactivity of 50 cannabinoid compounds. QSAR models were successfully built to predict the biological activities of these compounds, and compounds Ic14, Ic18, and Ic19 showed higher predicted biological activities than the main cannabinoid compounds Delta 9-THC and Delta 8-THC. Compound Ic21 stood out as having the highest predicted biological activity in interaction with the CB2 receptor.
JOURNAL OF MOLECULAR MODELING
(2023)
Article
Food Science & Technology
Sailing Chen, Shaowei Wang, Jingyi Zheng, Han Lu, Huiqian Chen, Yunbing Tang, Nan Wang, Yang Zhu, Yiyan Wang, Ping Duan, Ren-shan Ge
Summary: In this study, we found that bisphenols can inhibit the activity of 178-HSD1, with a stronger inhibition on human enzyme. Bisphenol H exhibited the most significant inhibitory effect compared to bisphenol A, and the inhibitory effect was correlated with the hydrophobicity of the compounds. Docking analysis and 3D-QSAR models revealed the key factors for the inhibition of steroid synthesis activity of 178-HSD1.
FOOD AND CHEMICAL TOXICOLOGY
(2023)
Article
Pharmacology & Pharmacy
Speranta Avram, Miruna Silvia Stan, Ana Maria Udrea, Catalin Buiu, Anca Andreea Boboc, Maria Mernea
Summary: Current treatment of depression involves using antidepressant synthetic drugs with side effects, while natural compounds may serve as an alternative solution. Through bioinformatics methods and 3D-ALMOND-QSAR models, the antidepressant effects of ten natural compounds were successfully predicted, with most compounds modulating SERT and fewer targeting 5-HT1A and D2 receptors.
Article
Biochemistry & Molecular Biology
Khandekar Mangala, Walhekar Vinayak, Choudhary Aasiya, Bagul Chandrakant, Muthal Amol, Dilip Kumar, Ravindra Kulkarni
Summary: This study used ligand-based and structure-based methods to develop new inhibitors of PIM-1 kinase as anticancer agents. 3D-QSAR analysis revealed the correlation between compound structures and biological activities. Molecular docking and dynamics simulations showed that compound 26 had the highest activity and interacted with the active site of PIM-1 kinase through hydrogen bonds. The results demonstrated the successful application of ligand and structure-based strategies in drug development.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Wenkun Zhuo, Zheng Lian, Wenzhe Bai, Yanrong Chen, Huanling Xia
Summary: In this study, 2D and 3D QSAR models were established to predict the anti-tumor activity of dipeptide-alkylated nitrogen-mustard compounds, and a series of new compounds were designed based on the models. The results showed satisfactory performance of both 2D and 3D QSAR models, and the 3D QSAR model successfully predicted compounds with high anti-tumor activity.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Sonu Benny, Prayaga Rajappan Krishnendu, Sunil Kumar, Vaishnav Bhaskar, Deepthi S. Manisha, Mohamed A. Abdelgawad, Mohammed M. Ghoneim, Ibrahim A. Naguib, Leena. K. Pappachen, Subin Mary Zachariah, Bijo Mathew, T. P. Aneesh
Summary: In this study, reliable models were generated and promising molecules were identified by combining QSAR modelling with the pharmacophore hypothesis-generating technique. The identified molecules were screened, and their chemical features for TS inhibitors were explored.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Agriculture, Multidisciplinary
Jinzhou Ren, Xia Ji, Wei Gao, Zhenwu Yu, Kun Li, Lixia Xiong, Na Yang, Yuxin Li, Zhengming Li, Zhijin Fan
Summary: Three-dimensional quantitative structure-activity relationship (3D-QSAR) is an important tool in new pesticide development. In this study, new insecticidal N-phenylpyrazoles were designed based on the 3D-QSAR of chlorantraniliprole analogues. Most of the synthesized compounds showed medium to excellent activity against different insect species. Compound III b exhibited similar activity against Mythimna separata as chlorantraniliprole, and showed higher potency against Plutella xylostella and Spodoptera frugiperda. Calcium imaging experiments and molecular docking confirmed the mode of action of these compounds.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Agriculture, Multidisciplinary
Pedro Alves Bezerra Morais, Karolinni B. Britto, Evandro Messias, Peterson de Andrade, Elias Werner, Adilson Vidal Costa, Valdemar Lacerda Jr, Christiano Jorge Gomes Pinheiro, Heberth de Paula, Warley de Souza Borges
Summary: To address the issues of weed infestation and herbicide resistance, the authors synthesized eight isatin derivatives using Click Chemistry. These derivatives were evaluated for their phytotoxic activity against two model plants, Lactuca sativa and Allium cepa. Six derivatives showed similar activity to the positive control trifluralin, with compound 8 being more active than trifluralin in L. sativa. ALS crystallographic structure analysis revealed the inhibitory activity of compounds 11 and 17 against A. cepa.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Vivek Makwana, Philip Ryan, Alpeshkumar K. Malde, Shailendra Anoopkumar-Dukie, Santosh Rudrawar
Summary: OGT is a key enzyme involved in the modification of various nuclear and cytosolic proteins with O-GlcNAc. Rational design of bisubstrate analogue inhibitors for OGT sheds light on the potential role of OGT in regulating cellular functions.
Article
Neurosciences
Matthew D. Figley, Weixi Gu, Jeffrey D. Nanson, Yun Shi, Yo Sasaki, Katie Cunnea, Alpeshkumar K. Malde, Xinying Jia, Zhenyao Luo, Forhad K. Saikot, Tamim Mosaiab, Veronika Masic, Stephanie Holt, Lauren Hartley-Tassell, Helen Y. McGuinness, Mohammad K. Manik, Todd Bosanac, Michael J. Landsberg, Philip S. Kerry, Mehdi Mobli, Robert O. Hughes, Jeffrey Milbrandt, Bostjan Kobe, Aaron DiAntonio, Thomas Ve
Summary: SARM1 is a nicotinamide adenine dinucleotide (NAD+)-cleaving enzyme that is activated by an increase in the ratio of NMN to NAD+, triggering axon destruction. The structural analysis showed that both NMN and NAD+ compete for binding to the auto inhibitory N-terminal armadillo repeat (ARM) domain of SARM1.
Article
Multidisciplinary Sciences
Max T. B. Clabbers, Susannah Holmes, Timothy W. Muusse, Parimala R. Vajjhala, Sara J. Thygesen, Alpeshkumar K. Malde, Dominic J. B. Hunter, Tristan Croll, Leonie Flueckiger, Jeffrey D. Nanson, Md Habibur Rahaman, Andrew Aquila, Mark S. Hunter, Mengning Liang, Chun Hong Yoon, Jingjing Zhao, Nadia A. Zatsepin, Brian Abbey, Emma Sierecki, Yann Gambin, Katryn J. Stacey, Connie Darmanin, Bostjan Kobe, Hongyi Xu, Thomas Ve
Summary: MyD88 and MAL are TLR adaptors that induce pro-inflammatory cytokine production, with the TIR domain of MAL forming filaments in vitro that nucleate the assembly of crystalline arrays of the MyD88 TIR domain. The structures of these assemblies were determined using MicroED and SFX techniques, showing the importance of the MyD88 interface residues for TLR4 signaling in vivo. The study provides insight into TLR signal transduction and compares the MicroED and SFX techniques.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Shaobo Zhang, Cheng Li, Robert G. Gilbert, Alpeshkumar K. Malde
Summary: This study used molecular dynamics simulations to build a model of the binding between rice GBSS and amylose, finding that starch/amylose fragments with 5 or 6 glucose units were suitable for modeling starch binding. Removing an interdomain disulfide on GBSS was found to affect the binding stability, and key residues that could affect the binding ability were identified.
Review
Pathology
Gargi Dixit, Arati Prabhu
Summary: PPARs play a crucial role in regulating metabolic events in our body, with their agonists and antagonists holding therapeutic significance. Understanding the molecular mechanisms of different PPAR isotypes in health and disease is essential for maximizing their therapeutic potential. Insights into the multifaceted therapeutic effects and underlying mechanisms of PPAR agonists and antagonists will guide future efforts in identifying novel molecules for metabolic, inflammatory, and immunotherapeutic diseases.
EXPERIMENTAL AND MOLECULAR PATHOLOGY
(2022)
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
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)
Article
Chemistry, Applied
Xiaoyan Tan, Shaobo Zhang, Alpeshkumar K. Malde, Xinle Tan, Robert G. Gilbert
Summary: This study investigates the effects of endogenous proteins on starch digestion kinetics in chickpeas. It identifies potential proteinaceous alpha-amylase inhibitors belonging to albumin, globulin, and glutelin and explores their binding mechanisms with porcine pancreatic alpha-amylase (PPA) using docking simulation. The results show that small peptides (<3 kDa) from the hydrolysis of endogenous proteins exhibit strong inhibitory activity on PPA. It is found that the different types of alpha-AIs inhibit PPA activity by interacting with specific regions of the enzyme, hindering the formation of enzyme-starch complexes and reducing starch digestibility.
FOOD HYDROCOLLOIDS
(2022)
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
Chemistry, Inorganic & Nuclear
Anil K. Gorle, Alpeshkumar K. Malde, Chih-Wei Chang, Premraj Rajaratnam, Mark von Itzstein, Susan J. Berners-Price, Nicholas P. Farrell
Summary: [H-1, N-15] HSQC 2D NMR spectroscopy was used to study the aquation and subsequent coordinate covalent binding of the trinuclear clinical agent triplatin with two disaccharides, GlcNS(6S)-GlcA and GlcNS(6S)-IdoA(2S). The rate constant for sulfate displacement of the aqua ligand is higher than that for carboxylate displacement. Molecular dynamics calculations suggest that extra hydrogen-bonding interactions with the more sulfated disaccharide may prevent or diminish sulfate binding of the triplatin moiety.
INORGANIC 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
Biochemistry & Molecular Biology
Shaobo Zhang, Xiaolei Fan, Alpeshkumar K. Malde, Robert G. Gilbert
Summary: This study used molecular dynamics simulations and free energy calculations to predict the binding of different GBSSI mutants to amylose fragments and to predict the effects of mutations on enzyme activity. It was found that mutants with negative binding energy are more likely to have higher enzyme activity and amylose content. This research is helpful in the development of grains with improved functional properties.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Multidisciplinary
Benjamin Bailly, Anil K. Gorle, Larissa Dirr, Alpeshkumar K. Malde, Nicholas P. Farrell, Susan J. Berners-Price, Mark von Itzstein
Summary: TriplatinNC is an antiviral agent that protects cells from viral entry by forming adducts with cell-surface glycosaminoglycans, opening new directions for metalloshielding antiviral drug development.
CHEMICAL COMMUNICATIONS
(2021)