Zero Hunger (SDG 2), Good Health & Well-being (SDG 3)
Design and synthesis of oxadiazole and indole-based allosteric Cyclin Dependent Kinase 2 inhibitor for non-toxic ovarian cancer chemotherapy Tahreem Liaqat 1 , Zainab Shahzad 1 , Hira Khalid 1* , Rashid Hussain 1 , Syed Adnan Ali 2 , Farina Hanif 2 , Lubna Khan 2 and Nazia Ahmed 2 1 Department of Chemistry, Forman Christian College University, Lahore-54600, Pakistan. 2 Department of Pharmacology & Pharmaceutical Chemistry, Faculty of Pharmacy, Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam, Selangor-42300, Malaysia. 3 Department of Biochemistry, Dow International Medical College Dow University of Health Sciences, Ojha campus. Karachi Pakistan. E-mail: hirakhalid@fccollege.edu.pk Ovarian cancer is the deadliest gynecologic malignancy and the seventh leading cause of cancer-related deaths among women worldwide. It arises due to mutations in tumor suppressor genes, leading to CDK2 overexpression and disruption of cell cycle regulation. Since CDK2 dysregulation is implicated in various cancers, it presents a promising target for cancer therapy. This study focused on synthesizing indole-based and oxadiazole-based compounds as potential allosteric CDK2 inhibitors using two reaction schemes. Molecular docking was performed against the CDK2 crystal structure (PDB: 3PXF) to evaluate binding affinities. The synthesized compounds—AO-ZS-01, AO-ZS-02, ZS-03, AO-ZS-05, and TL081—were then tested on ovarian cancer cell lines to assess their anticancer potential. Results demonstrated dose-dependent inhibition, indicating their effectiveness in targeting CDK2. These findings highlight the potential of the synthesized compounds as CDK2 inhibitors, laying the groundwork for further preclinical studies aimed at developing targeted therapies for ovarian cancer. Key words: Cyclin dependent Kinase2, CDK2, allosteric inhibitors, Ovarian Cancer, Drug Discovery
Fig 1: Molecular docking and anticancer profile of TL081
References 1. Nature Communications, 14, 3213, 1-13 2023 https://doi.org/10.1038/s41467-023-38732-x.
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