Medicinal Chemistry, Pharmacokinetics and Drug-Likeness Properties of Some Azetidinone Derivatives via Swiss-ADME Tool

Abstract: Azetidinone derivatives, known for their potent biological activities, have garnered significant attention in medicinal chemistry. Swiss ADME, a web-based computational tool, is used in the present study to assess the pharmacokinetics and drug-likeness profiles of certain azetidinone derivatives. A comprehensive in-silico analysis was conducted to predict key parameters such as absorption, distribution, metabolism, and excretion (ADME), alongside physicochemical properties, lipophilicity, water solubility, and bioavailability scores. The drug-likeness was assessed using Lipinski's Rule of Five and other medicinal chemistry filters. Results revealed that most of the azetidinone derivatives exhibit favourable pharmacokinetic profiles with high gastrointestinal absorption, moderate to high lipophilicity, and good oral bioavailability. Several compounds also complied with multiple drug-likeness filters, indicating promising lead-like characteristics. These results highlight the potential of Swiss ADME as a predictive tool in early-stage drug development and offer insightful information for the logical design and optimisation of azetidinone-based therapies.

Azetidinone, Lipinski's Rule, lipophilicity, bioavailability, Swiss ADME, in-silico

1. US5229381A - Substituted azetidinones as anti-inflammatory and antidegenerative agents - Google Patents [Internet]. Google.com. 1991 [cited 2024 Aug 14]. [Google Scholar] [Crossref]

2. Ulanowska, M., & Olas, B. (2021). Biological properties and prospects for the application of eugenol—a review. International journal of molecular sciences, 22(7), 3671. [Google Scholar] [Crossref]

3. Daina, A., Michielin, O., & Zoete, V. (2017). SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific reports, 7(1), 42717. [Google Scholar] [Crossref]

4. Radu, A. F., Negru, P. A., Radu, A., Tarce, A. G., Bungau, S. G., Bogdan, M. A., ... & Uivaraseanu, B. (2023). Simulation-based research on phytoconstituents of Embelia ribes targeting proteins with pathophysiological implications in rheumatoid arthritis. Life, 13(7), 1467. [Google Scholar] [Crossref]

5. Udugade, S. B., Doijad, R. C., & Udugade, B. V. (2019). In silico evaluation of pharmacokinetics, drug-likeness and medicinal chemistry friendliness of momordicin1: an active chemical constituent of momordica charantia. Journal of Advanced Scientific Research, 10(03 Suppl 1), 222-229. [Google Scholar] [Crossref]

6. O'Boyle, N. M., Banck, M., James, C. A., Morley, C., Vandermeersch, T., & Hutchison, G. R. (2011). Open Babel: An open chemical toolbox. Journal of cheminformatics, 3(1), 33. [Google Scholar] [Crossref]

7. Mahanthesh, M. T., Ranjith, D., Yaligar, R., Jyothi, R., Narappa, G., & Ravi, M. (2020). Swiss ADME prediction of phytochemicals present in Butea monosperma (Lam.) Taub. Journal of Pharmacognosy and Phytochemistry, 9(3), 1799-1809. [Google Scholar] [Crossref]

• Decision Tree and Automatic Linear Modeling Approaches to Predict Body Weight in Indigenous Sabi Sheep and Matebele Goat Females of Zimbabwe
• Microcontroller – Based Automatic Railway Crossing Control and Track Obstacle Monitoring System
• Modelling the Role of Absorptive Capacity in Foreign Direct Investment - Economic Growth Nexus: A Focus on South Africa’s Manufacturing Sector
• AI-Powered Wristband for Accurate BAC Monitoring Using Smart Data Fusion
• Climate Change Impacts on Different Regions