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<p>Lung cancer, the deadliest malignancy worldwide, causes 2.2 million cases and 1.8 million deaths annually, accounting for 18% of cancer deaths. Limited early detection, unaffordable treatments, and drug resistance lead to low survival rates, highlighting the urgent need for developing effective, resistance-proof therapies. In this study, we docked the DrugBank library against Lung Cancer Oxidoreductase, Chaperone, Transferase, and Hydrolase Proteins to identify a multitargeted drug candidate, resulting in identifying a promising drug candidate named Indenopyrazole with docking and MM\GBSA scores ranging from −7.337 to −11.62 and −17.82 to −60.38 kcal/mol, respectively. We also evaluated the interaction pattern of the drug candidate with Molecular Interaction Fingerprints and found that the most interacting residues with its counts are 4TRP, 3ASP, 3GLN, 3GLU, 3LYS, 3PHE, and 3TYR. The pharmacokinetics and comparison with standard values supported the candidate, followed by the density functional theory computations. The study was also validated for the WaterMap for water thermodynamics, and its role in binding pockets has also supported the idea that Indenopyrazole has a multitargeted potency. Further, we extended our studies with 100ns MD Simulation in water to analyse the deviations, fluctuations, and intermolecular interactions, and all the 1000 trajectories were evaluated for total complex energy and binding free energy with MM\GBSA concluding wonderful promising results in support of Indenopyrazole as a multitargeted drug candidate—however, its efficacy needs to be experimentally validated.</p>

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Evaluating the polypharmacological potency of indenopyrazole against lung cancer oxidoreductase, chaperone, transferase, and hydrolase proteins

  • 期刊论文

  • 发表日期：

    2025年5月9日

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  • Youssef Saeed Alghamdi,
  • Mutaib M. Mashraqi,
  • Ohud Alsalmi,
  • Afaf Awwadh Alharthi,
  • Amal F. Gharib

摘要

Lung cancer, the deadliest malignancy worldwide, causes 2.2 million cases and 1.8 million deaths annually, accounting for 18% of cancer deaths. Limited early detection, unaffordable treatments, and drug resistance lead to low survival rates, highlighting the urgent need for developing effective, resistance-proof therapies. In this study, we docked the DrugBank library against Lung Cancer Oxidoreductase, Chaperone, Transferase, and Hydrolase Proteins to identify a multitargeted drug candidate, resulting in identifying a promising drug candidate named Indenopyrazole with docking and MM\GBSA scores ranging from −7.337 to −11.62 and −17.82 to −60.38 kcal/mol, respectively. We also evaluated the interaction pattern of the drug candidate with Molecular Interaction Fingerprints and found that the most interacting residues with its counts are 4TRP, 3ASP, 3GLN, 3GLU, 3LYS, 3PHE, and 3TYR. The pharmacokinetics and comparison with standard values supported the candidate, followed by the density functional theory computations. The study was also validated for the WaterMap for water thermodynamics, and its role in binding pockets has also supported the idea that Indenopyrazole has a multitargeted potency. Further, we extended our studies with 100ns MD Simulation in water to analyse the deviations, fluctuations, and intermolecular interactions, and all the 1000 trajectories were evaluated for total complex energy and binding free energy with MM\GBSA concluding wonderful promising results in support of Indenopyrazole as a multitargeted drug candidate—however, its efficacy needs to be experimentally validated.