6th Commonwealth Chemistry Posters

Ovarian cancer is the most lethal gynecologic malignancy, driven in part by CDK2 overexpression that disrupts cell cycle control. Targeting CDK2 through selective inhibitors offers a promising therapeutic strategy. In this study, indole- and oxadiazole-based compounds were synthesized, characterized, and evaluated as allosteric CDK2 inhibitors. Molecular docking revealed strong binding affinities, particularly for AO-ZS-02 (–9.8 kcal/mol). Biological testing on ovarian cancer cell lines confirmed dose-dependent growth inhibition, with AO-ZS-02 showing the greatest potency. These findings highlight the potential of heterocyclic scaffolds as lead structures for developing selective, less toxic therapies against ovarian cancer.

References

Yang, L., Fang, D., Chen, H., Lu, Y., Dong, Z., Ding, H.-F., Jing, Q., Su, S.-B., & Huang, S. (2015). Cyclin-dependent kinase 2 is an ideal target for ovary tumors with elevated cyclin E1 expression. Oncotarget, 6(25), 20801–20812. https://doi.org/10.18632/oncotarget.4600
Faber, E. B., Tian, D., Burban, D., Levinson, N. M., Hawkinson, J. E., & Georg, G. I. (2020). Cooperativity Between Orthosteric Inhibitors and Allosteric Inhibitor 8-Anilino-1-Naphthalene Sulfonic Acid (ANS) in Cyclin-Dependent Kinase 2. ACS Chemical Biology, 15(7), 1759–1764. https://doi.org/10.1021/acschembio.0c00169

Abstract

CDK2 Inhibitors in available in market

Introduction

Design and synthesis of oxadiazole and indole-based allosteric cyclin dependent kinase 2 inhibitor for non-toxic ovarian cancer chemotherapy

Tahreem Liaqat¹, Hira Khalid¹*, Zainab Shahzad¹, Rashid Hussain¹, Syed Adnan Ali², Farina Hanif², Lubna Khan² and Nazia Ahmed²

¹Department of Chemistry, Forman Christian College University, Lahore-54600, Pakistan.

²Department of Pharmacology & Pharmaceutical Chemistry, Faculty of Pharmacy, Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam, Selangor-42300, Malaysia

²Department of Biochemistry, Dow International Medical College, Dow University of Health Sciences, Ojha campus. Karachi Pakistan

E-mail: tehreemliaqat99@gmail.com, hirakhalid@fccollege.edu.pk

Objective

Synthesis of small heterocyclic molecules that may show higher growth inhibitory potential to cure the diseases i.e. cancer

There is a need of inhibitor with high selectivity that may have low clinical resistivity

Methodology

Scheme1: Synthesis of 2-((5-(4-sulfamoylphenyl)-1,3,4-oxadiazol-2-yl)thio)-N-(2,4,5-trichlorophenyl)acetamide

Scheme2: Synthesis of 3-((2-(1H-indol-3-yl)ethyl)thio) -4-carbamoylbenzoic acid

Methodology

In this study, molecular docking was performed to evaluate the binding affinities of compounds against CDK2 using PDB ID: 3PXF.

PHE80

LEU66

LEU55

ILE52

ILE35

VAL154

LEU76

TYR179

LYS178

CYS177

ASN272

PRO271

TRP227

MET233

MTT Assay of synthesized compounds

Results/Conclusion

References

TL081 (indole-based) showed moderate growth inhibition at a moderate concentration.

The compounds were successfully synthesized, characterized, and biologically evaluated for growth inhibition.
AO_ZS_02 (oxadiazole-based) exhibited the highest growth inhibition.

The results highlight their potential as therapeutic growth inhibitors, warranting further mechanistic studies.

Acknowledgement

6th Commonwealth Chemistry Posters

Design and synthesis of oxadiazole and indole-based allosteric cyclin dependent kinase 2 inhibitor for non-toxic ovarian cancer chemotherapy

Poster Presenter

Authors

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