Quantitative Structure Activity Relationship (QSAR) modelling and Molecular Docking of Benzimidazole Analogues as Anticancer agents

Arunasalam, Raadhika (2022) Quantitative Structure Activity Relationship (QSAR) modelling and Molecular Docking of Benzimidazole Analogues as Anticancer agents. [Project Paper] (Submitted)

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Abstract

Cancer contributed to 18.1 million cases and almost 10 million deaths in 2020 and will keep increasing to 16.4 million by 2040. Cancer treatment till today is chemotherapy which may cause adverse effects to healthy somatic cells. Hence, there is a need for a new chemotherapeutic compound which can act as a new anti-cancer agent. Caspase-8 plays an important role in apoptosis mechanism and one of the cancer hallmarks. Benzimidazole is widely known due to its varying medicinal properties, however, it is a relatively new candidate as a potential anti-cancer agent. Objective: The aim of this study is to develop a validated QSAR model, predict the characteristics for higher biological activity and analyse possible interactions of synthesized compounds against caspase-8. Methodology: A validated QSAR model is created using hundred thirty-nine (139) benzimidazole compounds using genetic approximation function (GFA) method. Then, 10 QSAR models were computed, and external validation of chosen parameters was established. Finally, 3 QSAR models were chosen as the best models. Finally, five (5) synthesized benzimidazole analogues were tested for its binding affinity against caspase-8 using two software which are AutoDock and Achilles Blind Docking Server. Results: The statistical equation of QSAR model revealed that benzimidazole compounds containing subpopulation of amine groups, high number of hydrogen donors and exhibit superconductivity inclines towards higher biological activity in MCF7 cancer cell line. The molecular docking data also showed that all 5 synthesized benzimidazole analogues can bind against caspase-8 with 2 out of 5 compounds exhibiting highest binding affinity of 9.2 kcal/mol energy. Discussion: Based on QSAR model, amine subpopulation contributes highest towards benzimidazole analogues’ biological activity. Amine are weak bases which act as hydrogen donors and has electronegative elements allowing hydrogen bonding. Hydrogen bonds contribute to bioavailability of the drug as it affects diffusion, stability, recognition, and interaction. In addition, higher binding energy is also highly contributed by the amount of hydrogen bonds created during docking. Conclusion: Findings of QSAR analysis and molecular docking demonstrates the potential of benzimidazole analogues as anticancer agents.

Item Type:	Project Paper
Faculty:	Faculty of Medicine and Health Science
Depositing User:	Ms. Nor Safa'aton Saidin
Date Deposited:	22 Aug 2023 04:38
Last Modified:	22 Aug 2023 04:38
URI:	http://psaspb.upm.edu.my/id/eprint/1352

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