Article
Multidisciplinary Sciences
Rachel-Ann A. Garibsingh, Elias Ndaru, Alisa A. Garaeva, Yueyue Shi, Laura Zielewicz, Paul Zakrepine, Massimiliano Bonomi, Dirk J. Slotboom, Cristina Paulino, Christof Grewer, Avner Schlessinger
Summary: ASCT2 is up-regulated in cancer and plays a crucial role in promoting cell proliferation by modulating intracellular glutamine levels; Inhibiting nutrient uptake via ASCT2 could be a potential strategy for cancer therapy; We designed a series of unique ASCT2 inhibitors using computational modeling and cryo-EM, providing a framework for the development of cancer therapeutics targeting ASCT2.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Spectroscopy
Xiangrong Li, Linyu Han, Zhizhi Song, Ruonan Xu, Lixia Wang
Summary: This study investigates the interaction between transferrin and flavonols under physiological conditions using experimental and computational approaches. The results show that there is a static quenching mechanism between transferrin and flavonols with moderate affinity and binding constants ranging from 103-104 L/mol. The interaction is driven by both enthalpy and entropy, and the main force types involved include hydrophobic interaction, electrostatic force, and hydrogen bonds. These findings are important for understanding the potential and mechanism of flavonols as targeted cancer drugs.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2023)
Article
Pharmacology & Pharmacy
Antigoni E. Koletti, Konstantinos N. Kontogiannopoulos, Konstantinos Gardikis, Sophia Letsiou, Vassilios P. Papageorgiou, Andreana N. Assimopoulou
Summary: The chiral pair alkannin and shikonin and their ester derivatives can be incorporated in lipid-based nanocarriers for dermal applications, showing satisfactory release profiles and enhancing cell viability and antioxidant response in human dermal fibroblasts.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Powsali Ghosh, Ravi Singh, Ankit Ganeshpurkar, Rayala Swetha, Devendra Kumar, Sushil Kumar Singh, Ashok Kumar
Summary: The study aimed to identify DAPK1 inhibitors using a drug design method. Through screening and docking study, three potential inhibitors were obtained, which exhibited good stability and low toxicity under simulated conditions.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Engineering, Chemical
Shiyang Chai, Lei Zhang, Jian Du, Anjan K. Tula, Rafiqul Gani, Mario R. Eden
Summary: The study introduces a versatile modeling framework for chemical products, consisting of multiple submodels and an associated database, allowing for the creation of new models through data regression and machine-learning-based modeling. By breaking down chemical product design problems into different subproblems and applying appropriate models and solution approaches, feasible products can be identified and developed.
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Muhammad Zeeshan, Hasan Can Gulbalkan, Ozce Durak, Zeynep Pinar Haslak, Ugur Unal, Seda Keskin, Alper Uzun
Summary: This study presents an integrated computational-experimental hierarchical approach for selecting the best IL-MOF combination for gas separation applications. By using multiple computational tools, a highly performant IL-MOF combination was identified, paving the way for rational design and development of gas separation applications.
ADVANCED FUNCTIONAL MATERIALS
(2022)
Article
Pharmacology & Pharmacy
Sheida Afkham, Jalal Hanaee, Mostafa Zakariazadeh, Farzaneh Fathi, Samira Shafiee, Somaieh Soltani
Summary: The research found that the binding mechanism between Rosuvastatin and human serum albumin is dynamic, exothermic, and enthalpy-driven, primarily through hydrogen bonds and van der Waals interactions. The formation of this complex alters the protein conformation and exhibits strong interaction. The results from surface plasmon resonance experiments showed that Rosuvastatin and human serum albumin have a stable binding.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Engineering, Electrical & Electronic
Martino De Carlo, Giansergio Menduni, Angelo Sampaolo, Francesco De Leonardis, Vincenzo Spagnolo, Vittorio M. N. Passaro
Summary: Quartz enhanced photoacoustic spectroscopy (QEPAS) has gained interest in gas sensing technology due to high sensitivity from resonant tuning forks (QTFs) and sensor modularity. However, current experimental setups rely on free space optics, leading to alignment issues and large space requirements. A proposed QEPAS sensor design integrates the laser source and optical components for compactness and aims at miniaturization for mobile and drone sensing applications.
JOURNAL OF LIGHTWAVE TECHNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Joana Santos, Miguel Cardoso, Irina S. Moreira, Joao Goncalves, Joao D. G. Correia, Sandra Cabo Verde, Rita Melo
Summary: Biological therapies, such as recombinant proteins, are a promising approach towards precision medicine. Innovatively, the combination of in silico studies and experimental methods can optimize the production of recombinant proteins for targeted therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Luciane B. Silva, Elenilze F. B. Ferreira, Maryam, Jose M. V. Espejo-Roman, Glauber V. Costa, Josiane M. Cruz, Njogu S. Kimani, Josivan Costa, Jose A. H. M. N. Bittencourt, Jorddy Cruz, Joaquin M. Campos, Cleydson B. R. Santos
Summary: Acetylcholinesterase (AChE) enzymes are crucial in the development of Alzheimer's disease (AD). This study identified two promising compounds (ZINC16951574-LMQC2 and ZINC08342556-LMQC5) with potential hAChE activity through virtual screening and molecular docking. These compounds exhibited favorable drug-likeness profile, excellent lipid solubility, high bioavailability, and adequate pharmacokinetics.
Review
Pharmacology & Pharmacy
Ratul Bhowmik, Ajay Manaithiya, Bharti Vyas, Ranajit Nath, Kamal A. Qureshi, Seppo Parkkila, Ashok Aspatwar
Summary: This article discusses various techniques used in tuberculosis drug discovery, including computational approaches. It introduces different databases, methods, approaches, and software used in conducting QSAR, pharmacophore modeling, and molecular docking. The important molecules discovered using these computational approaches and drugs in clinical trials for tuberculosis are also discussed. Finally, the challenges and future perspectives of these techniques in drug discovery are summarized.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Chemistry, Physical
Andrea Scarperi, Elisa Carignani, Francesca Martini, Jan P. Embs, Jan Wasicki, Giovanni Barcaro, Marco Geppi, Aleksandra Pajzderska
Summary: The dynamic properties of carbimazole, a drug used in hyperthyroidism treatment, were investigated using solid-state nuclear magnetic resonance spectroscopy and quasielastic neutron scattering combined with periodic density functional theory and molecular dynamics simulations. These methods provided a comprehensive description of the internal carbimazole motions. The study found that in crystalline carbimazole, only the reorientations of the two methyl groups were active on the explored timescale. The combination of different techniques allowed for the quantitative characterization of these reorientations, which vary by almost 2 orders of magnitude in timescale, consistent with previous findings in similar chemical environments. These results may be particularly relevant in understanding the biochemical and biological activities of active pharmaceutical ingredients.
JOURNAL OF PHYSICAL CHEMISTRY C
(2023)
Article
Chemistry, Medicinal
Rafaqat Hussain, Wajid Rehman, Shoaib Khan, Aneela Maalik, Mohamed Hefnawy, Ashwag S. Alanazi, Yousaf Khan, Liaqat Rasheed, Roberta Rocca
Summary: A new series of thiazole derivatives incorporating an imidazopyridine moiety were synthesized and evaluated for their potential alpha-glucosidase activity. Several compounds showed superior activity against the targeted enzyme, with compounds 4a and 4o being the most potent inhibitors. Docking analysis was used to explore the binding mode of these compounds with the active site of alpha-glucosidase. The structures of the synthesized compounds were determined using various spectroscopic methods.
Article
Spectroscopy
Xiangrong Li, Hongyi Liu, Xinzhe Wu, Ruonan Xu, Xiaoyi Ma, Congxiao Zhang, Zhizhi Song, Yanru Peng, Tianjun Ni, Yongtao Xu
Summary: The study investigated the bindings of naringenin and naringin to trypsin and pepsin using multi-spectroscopy analysis and computational modeling approaches. The results showed that both compounds can quench the intrinsic fluorescence of the enzymes through a static quenching mechanism, with naringin binding more firmly than naringenin. Thermodynamic analysis indicated that the interactions are synergistically driven by enthalpy and entropy, with major forces being hydrophobic, electrostatic interactions, and hydrogen bonding.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2021)
Article
Engineering, Chemical
Zheng-Ce Xu, Xiao-Jian Dong, Jia-Ni Shen, Yi-Jun He
Summary: This article proposes an integrated experimental and modeling approach for evaluating surface crystallization on polymer coatings. Two models are developed and a parameter identification method is adopted. The effectiveness of the approach is validated and it is found that the parameter identification method can estimate model parameters properly and the coupled model can accurately predict surface crystallization.
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Fisayo A. Olotu, Mahmoud E. S. Soliman
Summary: The selective inhibition of aberrant Fibroblast Growth Factor Receptors (FGFRs) is a viable strategy for cancer treatment. A recent study discovered a new compound C11 that showed selective activity against FGFR1. Computational methods were used to investigate the mechanism of this selective activity. This study provides rational insights for the structure-based design of highly specific FGFR1 inhibitors.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Brenda Udosen, Opeyemi Soremekun, Abram Kamiza, Tafadzwa Machipisa, Cisse Cheickna, Olaposi Omotuyi, Mahmoud Soliman, Mamadou Wele, Oyekanmi Nashiru, Tinashe Chikowore, Segun Fatumo
Summary: High blood pressure is a major risk factor for cardiovascular diseases in populations including individuals of African ancestry. However, limited genetic studies have been conducted to explore the genetic mechanism driving this phenomenon. This study performed genome-wide association analyses and identified independent genetic variants associated with blood pressure traits in individuals of African ancestry. The findings provide important insights into the molecular mechanisms underlying the genetics of blood pressure and have implications for further research and fine-mapping of high-risk loci/variants.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Miah Roney, A. K. M. Moyeenul Huq, Abdul Rashid Issahaku, Mahmoud E. S. Soliman, Md. Sanower Hossain, Abu Hasnat Mustafa, Md. Alimul Islam, Amit Dubey, Aisha Tufail, Mohd Fadhlizil Fasihi Mohd Aluwi, Saiful Nizam Tajuddin
Summary: Dengue fever is a significant global public health concern, causing hundreds of thousands of hospitalizations and deaths each year. This study aimed to discover a new anti-dengue therapy by using computer-based approaches. Natural products were screened using a pharmacophore model, and compounds with potential inhibitory effects were identified through molecular docking. The lead compound demonstrated promising characteristics for further development as a drug candidate.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Virology
Mahmoud A. A. Ibrahim, Alaa H. M. Abdelrahman, Dina E. M. Mohamed, Khlood A. A. Abdeljawaad, Mohamed Ahmed Naeem, Gamal A. Gabr, Ahmed M. Shawky, Mahmoud E. S. Soliman, Peter A. Sidhom, Paul W. Pare, Mohamed-Elamir F. Hegazy
Summary: The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in over 6 million deaths. Marine natural products have been explored as potential sources of antiviral drug candidates. Through screening and molecular docking, chetomin (UMHMNP1403367) was identified as a promising 3CL(pro) inhibitor for COVID-19 treatment. Further in vivo and in vitro studies are warranted to assess its efficacy.
Review
Chemistry, Multidisciplinary
Narges Hosseini Nasab, Fereshteh Azimian, Hendrik G. Kruger, Song Ja Kim
Summary: Coumarins, heterocyclic compounds with a benzo-a-pyrone structure, are widely used in pharmacology, cosmetics, chemical, and medicinal industries. Various methods and reactions have been employed to synthesize coumarin derivatives. This review covers the reactions of 3-acetylcoumarin with different reagents and provides an overview of various reactions of 3-acetylcoumarin, including multicomponent, cycloaddition, α-halogenation, aldol condensation, reduction, and 1,2-addition reactions. The synthesis of different compounds starting from 3-acetylcoumarins and their biological activities are presented. This review serves as a valuable resource for researchers in this field.
ARABIAN JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Adeniyi T. T. Adewumi, Wande M. M. Oluyemi, Yemi A. A. Adekunle, Nonhlanhla Adewumi, Mohamed Issa Alahmdi, Mahmoud E. S. Soliman, Nader E. E. Abo-Dya
Summary: This study identifies six novel inhibitors of the KasA enzyme, a critical target in TB drug design. The compounds JFX, M1, M2, and M5 show stronger interactions with KasA and have good predicted inhibitory constants, drug-likeness, ADME, and synthetic accessibility. The findings provide potential lead-like molecules for future TB drugs.
Article
Biochemistry & Molecular Biology
Abdul Rashid Issahaku, Mahmoud A. A. Ibrahim, Namutula Mukelabai, Mahmoud E. S. Soliman
Summary: Muscle weakness is a common problem in patients with neurogenic neuromuscular diseases and leads to disability and even death. This study focuses on the investigation of Reldesemtiv, a second-generation small molecule activator, and its impact on fast skeletal muscle troponin complex through computational techniques. The results reveal that Reldesemtiv binding potentially enhances the compactness of troponin C, reducing exposure to solvent molecules and favoring the slow release of calcium ions, resulting in the sensitization of the subunit to calcium. Several key residues in the inhibitory subunit, including Arg113, Met116, Val114, and Met121, contribute significantly to the binding energy of Reldesemtiv. These findings provide valuable insights for the development of specific and potent small molecule activators for fast skeletal muscle.
Article
Chemistry, Organic
Srinivas Ambala, Kimberleigh B. Govender, Kamal K. Rajbongshi, Thavendran Govender, Hendrik G. Kruger, Tricia Naicker, Per I. Arvidsson
Summary: Here, an effective and efficient transition metal-free method for the N-arylation of primary sulfonimidamides was reported. The benzyne intermediates generated from silyl aryl triflates successfully coupled with the primary sulfonimidamides, resulting in good to excellent yields. In addition, by adding 18-crown-6, the scope of this method was extended to tertiary sulfonimidamides with moderate to low yields.
TETRAHEDRON LETTERS
(2023)
Article
Chemistry, Medicinal
Byron K. Peters, Nakita Reddy, Mbongeni Shungube, Letisha Girdhari, Sooraj Baijnath, Sipho Mdanda, Lloyd Chetty, Thandokuhle Ntombela, Thilona Arumugam, Linda A. Bester, Sanil D. Singh, Anil Chuturgoon, Per I. Arvidsson, Glenn E. M. Maguire, Hendrik G. Kruger, Tricia Naicker, Thavendran Govender
Summary: Fi-lactams are the most commonly prescribed antibiotics due to their potent antimicrobial activities, but their efficacy is threatened by the alarming rates of antimicrobial resistance, particularly in carbapenem-resistant Enterobacterales expressing metallo-fi-lactamases (MBLs). In this study, a cyclic zinc chelator called BP1 was developed, which restored the efficacy of meropenem against MBL-expressing bacteria and showed no toxicity to human cells. The study also demonstrated the therapeutic potential of BP1 in reducing bacterial load in infected mice. These findings propose a promising strategy to combat antimicrobial resistance.
ACS INFECTIOUS DISEASES
(2023)
Article
Infectious Diseases
Nakita Reddy, Letisha Girdhari, Mbongeni Shungube, Arnoldus C. Gouws, Byron K. Peters, Kamal K. Rajbongshi, Sooraj Baijnath, Sipho Mdanda, Thandokuhle Ntombela, Thilona Arumugam, Linda A. Bester, Sanil D. Singh, Anil Chuturgoon, Per I. Arvidsson, Glenn E. M. Maguire, Hendrik G. Kruger, Thavendran Govender, Tricia Naicker
Summary: This study evaluated the use of a novel beta-lactamase inhibitor, BP2, in combination with meropenem to overcome resistance in hard-to-treat infectious diseases caused by virulent bacteria expressing beta-lactamases. The results showed that BP2 enhanced the activity of meropenem, exhibiting bactericidal effects with a MIC of <= 1 mg/L and was safe to use at the tested concentrations. BP2 also demonstrated strong inhibitory activity against NDM-1 and VIM-2, specifically targeting MBLs. In a murine infection model, the combination of BP2 and meropenem showed significant efficacy. These promising pre-clinical results make BP2 a suitable candidate for further research and development as a metallo-beta-lactamase inhibitor (MBLI).
Article
Chemistry, Medicinal
Samuel K. Kwofie, Joseph Adams, Emmanuel Broni, Kweku S. Enninful, Clement Agoni, Mahmoud E. S. Soliman, Michael D. Wilson
Summary: This review explores the role of machine learning (ML) techniques, including Bayesian, support vector machine, random forest, and deep learning models, in predicting small molecule inhibitors of Ebola virus (EBOV). The underutilization of deep learning models in EBOV drug discovery is discussed, along with the potential of deep neural network as an ML algorithm for predicting anti-EBOV compounds. The importance of comprehensive data sources and the potential of ML-driven decision making in reducing compound attrition rates in drug development pipeline are highlighted.
Article
Chemistry, Multidisciplinary
Narges Hosseini Nasab, Hussain Raza, Young Seok Eom, Mubashir Hassan, Andrzej Kloczkowski, Lloyd Christopher Chetty, Hendrik Gert Kruger, Song Ja Kim
Summary: A series of 1,3,4-thiadiazole-thiazolidinone derivatives (7a-j) were synthesized and evaluated as carbonic anhydrase inhibitors. Compound 7i showed higher inhibitory activity (IC50 = 0.402 +/- 0.017 mu M) compared to the standard reference acetazolamide (IC50 = 0.998 +/- 0.046 mu M). Kinetic analysis revealed that compound 7i binds competitively to the target enzyme. Compound 7i also exhibited good conformational state and hydrogen bond interactions in the receptor binding pocket, according to molecular docking studies.
NEW JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Mbongeni Shungube, Ayanda K. Hlophe, Letisha Girdhari, Victor T. Sabe, Byron B. Peters, Nakita Reddy, Kehinde F. Omolabi, Lloyd Chetty, Thilona Arumugam, Anil Chuturgoon, Hendrik G. Kruger, Per I. Arvidsson, Hua-Li Qin, Tricia Naicker, Thavendran Govender
Summary: Beta-lactamases deactivate beta-lactam antibiotics through hydrolysis mechanism. This study developed 11 potential MBL inhibitors that successfully restored the effectiveness of meropenem against NDM-producing Klebsiella pneumoniae infections.
