Ong, Kang Kit and Ramle, Abdul Qaiyum and Ng, Min Phin and Lim, Siew Huah and Sim, Kae Shin and Tan, Chun Hoe (2024) Computational and In vitro Elucidation of Indolenine-barbituric Acid Zwitterions as Potential Chemotherapeutical Agents. Letters in Drug Design & Discovery, 21 (15). pp. 3076-3084. ISSN 1570-1808, DOI https://doi.org/10.2174/0115701808279494231206060106.
Full text not available from this repository.Abstract
Introduction: The continuous pursuit of novel chemotherapeutical agents with improved efficacy and reduced adverse effects remains a critical area of research despite advancements in chemotherapy. We have previously synthesized indolenine and barbituric acid zwitterion scaffolds 1-10 sustainably; however, their precise chemotherapeutical properties are still lacking. Methods: In this present work, we conducted in silico ADMET analyses, molecular docking calculations, DNA binding studies, and cytotoxicity assays on these zwitterions. Results and Discussion: Among the 10 zwitterions, zwitterion 3 bearing a methoxy group demonstrated the highest drug-likeness score, low toxicity, as well as no violation of Lipinski's rule of five and Veber's rule. Both molecular docking calculations and DNA binding studies suggested that the minor groove of DNA is the most probable molecular target of 3 among the others (i.e., topoisomerase and tubulin). In addition, zwitterion 3 exhibited selective cytotoxicity against a wide array of human cancer cell lines without noticeable effect against the normal human colon fibroblast CCD- 18Co. Conclusion: Overall, these preliminary findings from our combined computational and experimental strategy suggested that 3 remains promising for further elaboration as a chemotherapeutic agent.
| Item Type: | Article |
|---|---|
| Funders: | Ministry of Education, Malaysia (FRGS/1/2019/STG01/UM/02/23); (FP100-2019A), Universiti Sains Malaysia (304/PKIMIA/6315738) |
| Uncontrolled Keywords: | Cytotoxicity; DNA binding; drug-likeness; molecular docking; minor groove; cancer |
| Subjects: | Q Science > Q Science (General) Q Science > QD Chemistry |
| Divisions: | Faculty of Science > Institute of Biological Sciences Faculty of Science > Department of Chemistry |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 06 Jan 2025 01:26 |
| Last Modified: | 06 Jan 2025 01:26 |
| URI: | http://eprints.um.edu.my/id/eprint/47059 |
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