Predicting ADME Properties of Chemicals

Background: Coumarin is a fused ring system and possesses enormous capability of targeting various receptors participating in cancer pathway. Coumarin and its derivatives were found to exhibit very rare toxicity and other side effects. It has been found its immense anticancer potential depends on the nature of group present and its pattern of substitution on the basic nucleus. Objectives: Synthesis of C-4 substituted coumarin derivatives and to study their molecular interactions with ERα for anticancer activity for Breast Cancer. Method: C-4 substituted coumarins analogues (1-10) have been synthesized using conventional heating and microwave irradiation. Using Schrodinger software molecular modeling studies were carried out and ADME properties of the compounds were predicted. Results: All the synthesized compounds have shown better G-Score (-6.87 to -8.43 kcal/mol) as compared to the standard drug tamoxifen (-5.28kcal/mol) and auraptene (-3.89kcal/mol). Molecular docking suggests that all compounds fit in the active site of protein as they have the same hydrophobic pocket as standard drug tamoxifen, and have an acceptable range of ADME properties. Conclusion: Microwave-assisted synthesis showed better results as compared to conventional heating. In-silico studies revealed that all the compounds befit in the active site of protein. ADME properties showed that all compounds are in allowable limits for human oral absorption. In future, there is a possibility of in-vitro and in-vivo studies of the synthesized compounds.

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Comparative in silico modeling of environmental and therapeutic classes of perfluorinated chemicals (PFCS): ADME properties, virtual receptor profiling and generalized PBPK models

Reproductive Toxicology ◽

10.1016/j.reprotox.2008.11.065 ◽

2009 ◽

Vol 27 (3-4) ◽

pp. 419-420 ◽

Cited By ~ 1

Author(s):

Michael-Rock Goldsmith ◽

Rogelio Tornero-Velez ◽

Thomas R. Transue ◽

Stephen B. Little ◽

James R. Rabinowitz ◽

...

Keyword(s):

In Silico ◽

Pbpk Models ◽

In Silico Modeling ◽

Perfluorinated Chemicals ◽

Adme Properties

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The Position of ADME Predictions in Multi-Objective QSAR

International Journal of Quantitative Structure-Property Relationships ◽

10.4018/ijqspr.2021010101 ◽

2021 ◽

Vol 6 (1) ◽

pp. 1-8

Author(s):

Anna Tsantili-Kakoulidou

Keyword(s):

Drug Efficacy ◽

Clinical Development ◽

Efficacy And Safety ◽

Huge Amount ◽

Multi Objective ◽

Drug Candidates ◽

Drug Molecules ◽

Qsar Models ◽

Adme Properties ◽

Single Objective

ADME properties and toxicity predictions play an essential role in prioritization and optimization of drug molecules. According to recent statistics, drug efficacy and safety are principal reasons for drug failure. In this perspective, the position of ADME predictions in the evolution of traditional QSAR from the single objective of biological activity to a multi-task concept is discussed. The essential features of ADME and toxicity QSAR models are highlighted. Since such models are applied to prioritize existing or virtual project compounds with already established or predicted target affinity, a mechanistic interpretation, although desirable, is not a primary goal. However, a broad applicability domain is crucial. A future challenge with multi-objective QSAR is to adapt to the realm of big data by integrating techniques for the exploitation of the continuously increasing number of ADME data and the huge amount of clinical development endpoints for the sake of efficacy and safety of new drug candidates.

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Natural products as inhibitors of COVID-19 main protease – A virtual screening by molecular docking

10.21203/rs.3.rs-57351/v1 ◽

2020 ◽

Author(s):

Marzieh omrani ◽

Mohammad Bayati ◽

Parvaneh Mehrbod ◽

Samad Nejad-Ebrahimi

Keyword(s):

Natural Products ◽

Virtual Screening ◽

High Throughput ◽

Herbal Medicines ◽

Respiratory Illness ◽

Fast Method ◽

Main Protease ◽

Glide Docking ◽

Adme Properties ◽

High Throughput Virtual Screening

Abstract Background: The novel coronavirus (2019-nCoV) causes a severe respiratory illness that was unknown in the human before. Its alarmingly quick transmission to many countries across the world resulted in a worldwide health emergency. It has caused a notable percentage of morbidity and mortality. Therefore, an imminent need for drugs to combat this disease has been increased. Global collaborative efforts from scientists are underway to find a therapy to treat infections and reduce death cases. Herbal medicines and purified natural products have been reported to have antiviral activity against Coronaviruses (CoVs).Methods: In this study, a High Throughput Virtual Screening (HTVS) protocol was used as a fast method on the discovery of novel drug candidates as the COVID-19 main protease inhibitors. Over 180,000 natural product-based compounds were obtained from the ZINC database and virtually screened against the COVID-19 main protease. In this study, the Glide docking program was applied for high throughput virtual screening. Extra precision (XP) and in a combination of Prime module, induced-fit docking (IFD) approach was also used. Additionally, the ADME properties of all compounds were analyzed, and the final selection was carried out based on the Lipinski rule of five. Results: The nineteen compounds were selected and introduced as new potential inhibitors. The compound ZINC08765174 (1-[3-(1H-indol-3-yl) propanoyl]-N-(4-phenylbutan-2-yl)piperidine-3-carboxamide) showed a strong binding affinity (-11.5 kcal/mol) to the crucial residues of COVID-19 main protease comparing to peramivir (-9.8 kcal/mol) as a positive control.Conclusions: The excellent ADME properties proposed the opportunity of this compound to be a promising candidate for the treatment of COVID-19.

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Characterization of in Vitro ADME Properties of Diosgenin and Dioscin from Dioscorea villosa

Planta Medica ◽

10.1055/s-0033-1350699 ◽

2013 ◽

Vol 79 (15) ◽

pp. 1421-1428 ◽

Cited By ~ 9

Author(s):

Vamshi Manda ◽

Bharathi Avula ◽

Zulfiqar Ali ◽

Yan-Hong Wong ◽

Troy Smillie ◽

...

Keyword(s):

Adme Properties

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