Design, Synthesis, and Biological Evaluation of Novel Monoamine Oxidase-A Inhibitors Targeting Lung Cancer Followed by Investigation of the Molecular Mechanisms using Mass Spectrometry-based Metabolomics and IR-Microspectroscopy
- مجال مشروع البحث–الرئيسي
- العلوم الطبية والصحية
- مجال مشروع البحث–الثانوي
- العلوم الصيدلانية
- المؤسسة العلمية
- الجامعة الأردنية
- المحافظة
- عمان
- قيمة الدعم
- JD20000
- سنة الدعم
- 2020
- حالة المشروع
- ما زال البحث قائما
- البحث منشور
- (1)Aljanabi, R., Alsous, L., Sabbah, D. A., Gul, H. I., Gul, M., & Bardaweel, S. K. (2021). Monoamine Oxidase (MAO) as a Potential Target for Anticancer Drug Design and Development. Molecules, 26(19), 6019.
(2) Bardaweel, S., Aljanabi, R., Sabbah, D., & Sweidan, K. (2022). Design, Synthesis, and Biological Evaluation of Novel MAO-A Inhibitors Targeting Lung Cancer. Molecules, 27(9), 2887.
- ملخص عن مشروع البحث
- (1) Monoamine oxidases (MAOs) are oxidative enzymes that catalyze the conversion of biogenic amines into their corresponding aldehydes and ketones through oxidative deamination. Owing to the crucial role of MAOs in maintaining functional levels of neurotransmitters, the implications of its distorted activity have been associated with numerous neurological diseases. Recently, an unanticipated role of MAOs in tumor progression and metastasis has been reported. The chemical inhibition of MAOs might be a valuable therapeutic approach for cancer treatment. In this review, we reported computational approaches exploited in the design and development of selective MAO inhibitors accompanied by their biological activities. Additionally, we generated a pharmacophore model for MAO-A active inhibitors to identify the structural motifs to invoke an activity.
https://www.mdpi.com/1420-3049/26/19/6019
(2) Lung cancer is one of the most common causes of cancer-related deaths worldwide. Monoamine Oxidase-A (MAO-A) enzyme mediates the production of reactive oxygen species (ROS) that trigger DNA damage and oxidative injury of cells resulting in tumor initiation and progression. Available MAO-A inhibitors are used as antidepressants, however, their role as anticancer agents is still under investigation. Ligand- and structure-based drug design approaches guided the discovery and development of novel MAO-A inhibitors. A series of 1H indole-2-carboxamide derivatives was prepared and characterized using 1H-NMR, 13C-NMR, and IR. The antiproliferative effects of MAO-A inhibitors were evaluated using the cell viability assay (MTT), and MAO-A activity was evaluated using MAO-A activity assay. The presumed inhibitors significantly inhibited the growth of lung cell lines in a dose- and time dependent manner. The half maximal inhibitory concentration (IC50) values of MAO-A inhibitors (S1, S2, S4, S7, and S10) were 33.37, 146.1, 208.99, 307.7, and 147.2 µM, respectively, in A549. Glide docking against MAO-A showed that the derivatives accommodate MAO-A binding cleft and engage with key binding residues. MAO-A inhibitors provide significant and consistent evidence on MAO-A activity in lung cancer and present a potential target for the development of new chemotherapeutic agents.
https://www.mdpi.com/1420-3049/27/9/2887
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الاسم الكامل للباحث الرئيسي
د.سناء بردويل
الجنس
انثى
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الباحث المشارك الأول
د. لينا ذهبية
الجنس
انثى
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الباحث المشارك الثاني
د. ديما عزام
الجنس
انثى
المشاريع ذات صلة