Does DMSO affect the conformational changes of drug molecules in supercritical CO2 Media?

Khodov, Ilya A.; Belov, Konstantin V.; Krest’yaninov, М. А.; Sobornova, V.V.; Dyshin, A. A.; Киселев, М. Г.

doi:10.1016/j.molliq.2023.122230

Cited by 9 publications

(4 citation statements)

References 79 publications

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“…Unfortunately, the extremely low solubility of cabotegravir in water prevents a comprehensive NMR characterization of this drug in aqueous solutions. Therefore, we have taken a two-step approach, which uses DMSO [ 25 , 26 ] as a “broker” solvent as described below, to extract the structural information.…”

Section: Resultsmentioning

confidence: 99%

Multitasking Pharmacophores Support Cabotegravir-Based Long-Acting HIV Pre-Exposure Prophylaxis (PrEP)

Wan,

Shi,

Gong

et al. 2024

Molecules

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Cabotegravir is an integrase strand transfer inhibitor (INSTI) for HIV treatment and prevention. Cabotegravir-based long-acting pre-exposure prophylaxis (PrEP) presents an emerging paradigm for infectious disease control. In this scheme, a combination of a high efficacy and low solubility of anti-infection drugs permits the establishment of a pharmaceutical firewall in HIV-vulnerable groups over a long period. Although the structure-activity-relationship (SAR) of cabotegravir as an INSTI is known, the structural determinants of its low solubility have not been identified. In this work, we have integrated multiple experimental and computational methods, namely X-ray diffraction, solid-state NMR (SSNMR) spectroscopy, solution NMR spectroscopy, automated fragmentation (AF)-QM/MM and density functional theory (DFT) calculations, to address this question. The molecular organization of cabotegravir in crystal lattice has been determined. The combination of very-fast magic-angle-sample-spinning (VF MAS) SSNMR and solution NMR, as supported by AF-QM/MM and DFT calculations, permits the identification of structural factors that contribute to the low aqueous solubility of cabotegravir. Our study reveals the multitasking nature of pharmacophores in cabotegravir, which controls the drug solubility and, meanwhile, the biological activity. By unraveling these function-defining molecular features, our work could inspire further development of long-acting HIV PrEP drugs.

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Section: Resultsmentioning

confidence: 99%

Multitasking Pharmacophores Support Cabotegravir-Based Long-Acting HIV Pre-Exposure Prophylaxis (PrEP)

Wan,

Shi,

Gong

et al. 2024

Molecules

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“…Notable examples include high-pressure nuclear magnetic resonance (NMR) spectroscopy and techniques such as nuclear Overhauser effect spectroscopy (NOESY). The increased knowledge of molecular structure is made possible by conformation management, and this knowledge can influence various aspects of pharmaceuticals, including their bioavailability [116,117].…”

Section: Challenges and Prospects In Drug Bioavailability Researchmentioning

confidence: 99%

The Bioavailability of Drugs—The Current State of Knowledge

Stielow,

Witczyńska,

Kubryń

et al. 2023

Molecules

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Drug bioavailability is a crucial aspect of pharmacology, affecting the effectiveness of drug therapy. Understanding how drugs are absorbed, distributed, metabolized, and eliminated in patients’ bodies is essential to ensure proper and safe treatment. This publication aims to highlight the relevance of drug bioavailability research and its importance in therapy. In addition to biochemical activity, bioavailability also plays a critical role in achieving the desired therapeutic effects. This may seem obvious, but it is worth noting that a drug can only produce the expected effect if the proper level of concentration can be achieved at the desired point in a patient’s body. Given the differences between patients, drug dosages, and administration forms, understanding and controlling bioavailability has become a priority in pharmacology. This publication discusses the basic concepts of bioavailability and the factors affecting it. We also looked at various methods of assessing bioavailability, both in the laboratory and in the clinic. Notably, the introduction of new technologies and tools in this field is vital to achieve advances in drug bioavailability research. This publication also discusses cases of drugs with poorly described bioavailability, providing a deeper understanding of the complex challenges they pose to medical researchers and practitioners. Simultaneously, the article focuses on the perspectives and trends that may shape the future of research regarding bioavailability, which is crucial to the development of modern pharmacology and drug therapy. In this context, the publication offers an essential, meaningful contribution toward understanding and highlighting bioavailability’s role in reliable patient treatment. The text also identifies areas that require further research and exploration.

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“…Supercritical carbon dioxide (scCO 2 ) has demonstrated significant efficacy in various fields including extraction of essential oil, − seed oil, − nanoparticle formation, − impregnation, − control of polymorphic forms, − polymer synthesis, etc.…”

Section: Introductionmentioning

confidence: 99%

Prediction of Drug-like Compounds Solubility in Supercritical Carbon Dioxide: A Comparative Study between Classical Density Functional Theory and Machine Learning Approaches

Makarov,

Kalikin,

Budkov

2024

Ind. Eng. Chem. Res.

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Supercritical carbon dioxide (scCO 2 ) plays an essential role in various technological procedures, making the solubility of drugs in scCO 2 a crucial aspect of the drug formulation process. This study focuses on utilizing theoretical approaches to predict the solubility of drug-like compounds in scCO2 in order to select the optimum parameters for subsequent experimental procedures. Several machine learning models were developed and compared with a previously established theoretical approach based on classical density functional theory (cDFT). The CatBoost model, utilizing alvaDesc descriptors, demonstrated reasonably accurate predictions for the solubility of 187 drugs (AARD = 1.8%). Meanwhile, the CatBoost model, incorporating CDK descriptors and melting points of drugs as input parameters, exhibited satisfactory accuracy (AARD = 14.3%) in extrapolating predictions for new compounds. Comparing the results between the machine learning approach and the cDFT-based one revealed, on average, a higher accuracy and faster prediction speed for the former. However, cDFT demonstrated a more physical behavior of solubility isotherms compared with the machine learning models. This was particularly evident when the ML models struggled to accurately extrapolate solubility values beyond the experimental range of parameters in the supercritical state. Model CatBoost/CDK is freely accessible at http://chem-predictor.isc-ras.ru/ individual/scco/.

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Does DMSO affect the conformational changes of drug molecules in supercritical CO2 Media?

Cited by 9 publications

References 79 publications

Multitasking Pharmacophores Support Cabotegravir-Based Long-Acting HIV Pre-Exposure Prophylaxis (PrEP)

Multitasking Pharmacophores Support Cabotegravir-Based Long-Acting HIV Pre-Exposure Prophylaxis (PrEP)

The Bioavailability of Drugs—The Current State of Knowledge

Prediction of Drug-like Compounds Solubility in Supercritical Carbon Dioxide: A Comparative Study between Classical Density Functional Theory and Machine Learning Approaches

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