| Title: | "Deep eutectic solvent mediated synthesis of 3,4-dihydropyrimidin-2(1H)-ones and evaluation of biological activities targeting neurodegenerative disorders" |
| Author(s): | Saleem Khan M; Asif Nawaz M; Jalil S; Rashid F; Hameed A; Asari A; Mohamad H; Ur Rehman A; Iftikhar M; Iqbal J; Al-Rashida M; |
| Address: | "Department of Chemistry, Forman Christian College (A Chartered University), Ferozepur Road, 54600 Lahore, Pakistan. Department of Physics, University of Sahiwal, Sahiwal 57000, Pakistan. Electronic address: masif@uosahiwal.edu.pk. Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan. Department of Chemistry, University of Sahiwal, Sahiwal 57000, Pakistan. Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, 21030 Kuala Nerus, Terengganu, Malaysia. Institute of Marine Biotechnology, Universiti Malaysia Terengganu, 21030 Kuala Nerus, Terengganu, Malaysia. Department of Pharmacy, Forman Christian College (A Chartered University), Ferozepur Road, 54600 Lahore, Pakistan. School of Chemical Engineering, Nanjing University of Science and Technology, Xiaoling Wei, 210094 Nanjing, PR China. Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan. Electronic address: drjamshed@ciit.net.pk. Department of Chemistry, Forman Christian College (A Chartered University), Ferozepur Road, 54600 Lahore, Pakistan. Electronic address: mariyarashida@fccollege.edu.pk" |
| DOI: | 10.1016/j.bioorg.2021.105457 |
| ISSN/ISBN: | 1090-2120 (Electronic) 0045-2068 (Linking) |
| Abstract: | "Substitution of hazardous and often harmful organic solvents with 'green' and 'sustainable' alternative reaction media is always desirous. Ionic liquids (IL) have emerged as valuable and versatile liquids that can replace most organic solvents in a variety of syntheses. However, recently new types of low melting mixtures termed as Deep Eutectic Solvents (DES) have been utilized in organic syntheses. DES are non-volatile in nature, have sufficient thermal stability, and also have the ability to be recycled and reused. Hence DES have been used as alternative reaction media to perform different organic reactions. The availability of green, inexpensive and easy to handle alternative solvents for organic synthesis is still scarce, hence our interest in DES mediated syntheses. Herein we have investigated Biginelli reaction in different DES for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones. Monoamine oxidases and cholinesterases are important drug targets for the treatment of various neurological disorders such as Alzheimer's disease, Parkinson's disease, depression and anxiety. The compounds synthesized herein were evaluated for their inhibitory potential against these enzymes. Some of the compounds were found to be highly potent and selective inhibitors. Compounds 1 h and 1c were the most active monoamine oxidase A (MAO A) (IC(50) = 0.31 +/- 0.11 microM) and monoamine oxidase B (MAO B) (IC(50) = 0.34 +/- 0.04 microM) inhibitors respectively. All compounds were selective AChE inhibitors and did not inhibit BChE (<29% inhibition). Compound 1 k (IC(50) = 0.13 +/- 0.09 microM) was the most active AChE inhibitor" |
| Keywords: | "Acetylcholinesterase/*metabolism Cholinesterase Inhibitors/chemical synthesis/chemistry/*pharmacology Deep Eutectic Solvents/chemistry Dose-Response Relationship, Drug Humans Molecular Docking Simulation Molecular Structure Monoamine Oxidase/*metabolism M;" |
| Notes: | "MedlineSaleem Khan, Maria Asif Nawaz, Muhammad Jalil, Saquib Rashid, Faisal Hameed, Abdul Asari, Asnuzilawati Mohamad, Habsah Ur Rehman, Atta Iftikhar, Mehwish Iqbal, Jamshed Al-Rashida, Mariya eng Research Support, Non-U.S. Gov't 2021/11/20 Bioorg Chem. 2022 Jan; 118:105457. doi: 10.1016/j.bioorg.2021.105457. Epub 2021 Oct 29" |
