In-silico design, pharmacophore-based screening, and molecular docking studies reveal that benzimidazole-1,2,3-triazole hybrids as novel EGFR inhibitors targeting lung cancer

References

• Abad-Zapatero, C. (2007). Ligand efficiency indices for effective drug discovery. Expert Opinion on Drug Discovery, 2(4), 469–488. https://doi.org/10.1517/17460441.2.4.469
   PubMed Web of Science ®Google Scholar
• Abbas, F., Ali, U., Muhammad Rizwan Ahmad, H., Tallat, A., Shehzad, A., Zeb, Z., Hussain, I., Saeed, A., & Tariq, M. (2022). Role of iodo-substituted subphthalocyanine (Subpcs) π-conjugated aromatic N-fused di-iminoisonidole units on the performance of non-fullerene small organic solar cells. Computational and Theoretical Chemistry, 1207, 113508. https://doi.org/10.1016/j.comptc.2021.113508
   Web of Science ®Google Scholar
• Abughanimeh, O., Kaur, A., el Osta, B., & Ganti, A. K. (2022). Novel targeted therapies for advanced non-small lung cancer. Seminars in Oncology, 49(3–4), 326–336. https://doi.org/10.1053/j.seminoncol.2022.03.003
   Web of Science ®Google Scholar
• Ahirwar, D. K., Peng, B., Charan, M., Misri, S., Mishra, S., Kaul, K., Sassi, S., Gadepalli, V. S., Siddiqui, J., Miles, W. O., Ganju, R. K., Ahirwar, D. K., & Ganju, R. K. (2022). Slit2/Robo1 signaling inhibits small-cell lung cancer by targeting β-catenin signaling in tumor cells and macrophages. Molecular Oncology, 17(5), 839–856. https://doi.org/10.1002/1878-0261.13289
   Web of Science ®Google Scholar
• Ahmed Saleh Alzahrani, S., Nazreen, S., Elhenawy, A. A., Neamatallah, T., & Mahboob, M. (2022). Synthesis, biological evaluation, and molecular docking of new benzimidazole-1,2,3-triazole hybrids as antibacterial and antitumor agents. Polycyclic Aromatic Compounds, 43(4), 3380–3391. https://doi.org/10.1080/10406638.2022.2069133
   Web of Science ®Google Scholar
• Akhtar, J., Khan, A. A., Ali, Z., Haider, R., & Shahar Yar, M. (2017). Structure-activity relationship (SAR) study and design strategies of nitrogen-containing heterocyclic moieties for their anticancer activities. European Journal of Medicinal Chemistry, 125, 143–189. https://doi.org/10.1016/j.ejmech.2016.09.023
   PubMed Web of Science ®Google Scholar
• Alam, M. M. (2022). 1,2,3-triazole hybrids as anticancer agents: A review. Archiv Der Pharmazie, 355(1), e2100158. https://doi.org/10.1002/ardp.202100158
   PubMed Web of Science ®Google Scholar
• Ali, A. M., Tawfik, S. S., Mostafa, A. S., & Massoud, M. A. M. (2022). Benzimidazole-based protein kinase inhibitors: Current perspectives in targeted cancer therapy. Chemical Biology & Drug Design, 100(5), 656–673. https://doi.org/10.1111/CBDD.14130
   PubMed Web of Science ®Google Scholar
• Ali, U., Tariq, A., Kiran, A., Abbas, F., & Khalil, M. T. (2021). Tuning the absorption and optoelectronic properties of naphthalene diimide based solar cells with non-fullerene acceptors. Chemical Papers, 75(8), 4327–4336. https://doi.org/10.1007/s11696-021-01671-2
   Web of Science ®Google Scholar
• Almehmadi, M. A., Aljuhani, A., Alraqa, S. Y., Ali, I., Rezki, N., Aouad, M. R., & Hagar, M. (2021). Design, synthesis, DNA binding, modeling, anticancer studies and DFT calculations of Schiff bases tethering benzothiazole-1,2,3-triazole conjugates. Journal of Molecular Structure, 1225, 129148. https://doi.org/10.1016/j.molstruc.2020.129148
   Web of Science ®Google Scholar
• Alzahrani, H. A., Alam, M. M., Elhenawy, A. A., Malebari, A. M., & Nazreen, S. (2022). Synthesis, antiproliferative, docking and DFT studies of benzimidazole derivatives as EGFR inhibitors. Journal of Molecular Structure, 1253, 132265. https://doi.org/10.1016/j.molstruc.2021.132265
   Web of Science ®Google Scholar
• Avci, E. (2012). A new expert system for diagnosis of lung cancer: Gda-ls-svm. Journal of Medical Systems, 36(3), 2005–2009. https://doi.org/10.1007/s10916-011-9660-y
   PubMed Web of Science ®Google Scholar
• Beau-Faller, M., Prim, N., Ruppert, A.-M., Nanni-Metéllus, I., Lacave, R., Lacroix, L., Escande, F., Lizard, S., Pretet, J.-L., Rouquette, I., de Crémoux, P., Solassol, J., de Fraipont, F., Bièche, I., Cayre, A., Favre-Guillevin, E., Tomasini, P., Wislez, M., Besse, B., … Cadranel, J. (2014). Rare EGFR exon 18 and exon 20 mutations in non-small-cell lung cancer on 10 117 patients: A multicentre observational study by the French ERMETIC-IFCT network. Annals of Oncology : official Journal of the European Society for Medical Oncology, 25(1), 126–131. https://doi.org/10.1093/annonc/mdt418
   PubMed Web of Science ®Google Scholar
• Bembenek, S. D., Tounge, B. A., & Reynolds, C. H. (2009). Ligand efficiency and fragment-based drug discovery. Drug Discovery Today, 14(5–6), 278–283. https://doi.org/10.1016/j.drudis.2008.11.007
   PubMed Web of Science ®Google Scholar
• Bistrović, A., Krstulović, L., Harej, A., Grbčić, P., Sedić, M., Koštrun, S., Pavelić, S. K., Bajić, M., & Raić-Malić, S. (2018). Design, synthesis and biological evaluation of novel benzimidazole amidines as potent multi-target inhibitors for the treatment of non-small cell lung cancer. European Journal of Medicinal Chemistry, 143, 1616–1634. https://doi.org/10.1016/j.ejmech.2017.10.061
   PubMed Web of Science ®Google Scholar
• Bronte, G., Rizzo, S., la Paglia, L., Adamo, V., Siragusa, S., Ficorella, C., Santini, D., Bazan, V., Colucci, G., Gebbia, N., & Russo, A. (2010). Driver mutations and differential sensitivity to targeted therapies: A new approach to the treatment of lung adenocarcinoma. Cancer Treatment Reviews, 36, S21–S29. https://doi.org/10.1016/S0305-7372(10)70016-5
   PubMed Web of Science ®Google Scholar
• Buchwald, P. (2010). Small-molecule protein–protein interaction inhibitors: Therapeutic potential in light of molecular size, chemical space, and ligand binding efficiency considerations. IUBMB Life, 62(10), 724–731. https://doi.org/10.1002/iub.383
   PubMed Web of Science ®Google Scholar
• Chai, J. Y., Jung, B. K., & Hong, S. J. (2021). Albendazole and mebendazole as anti-parasitic and anti-cancer agents: An update. Korean Journal of Parasitology, 59(3), 189–225. https://doi.org/10.3347/KJP.2021.59.3.189
   PubMed Web of Science ®Google Scholar
• Chang, J. W. C., Huang, C. Y., Fang, Y. F., Chang, C. F., Yang, C. T., Kuo, C. H. S., Hsu, P., C., & Wu, C. E. (2022). Risk stratification using a novel nomogram for 2190 EGFR-mutant NSCLC patients receiving the first or second generation EGFR-TKI. Cancers, 14(4), 977. https://doi.org/10.3390/cancers14040977
   PubMed Web of Science ®Google Scholar
• Chaudhari, R., & Li, Z. (2015). PyMine: A PyMOL plugin to integrate and visualize data for drug discovery bioinformatics. BMC Research Notes, 8(1), 517. https://doi.org/10.1186/S13104-015-1483-3
   PubMedGoogle Scholar
• Cooper, Z. D. (2016). Adverse effects of synthetic cannabinoids: Management of acute toxicity and withdrawal. Current Psychiatry Reports, 18(5), 52. https://doi.org/10.1007/s11920-016-0694-1
   PubMed Web of Science ®Google Scholar
• Cortes-Ciriano, I. (2016). Benchmarking the predictive power of ligand efficiency indices in QSAR. Journal of Chemical Information and Modeling, 56(8), 1576–1587. https://doi.org/10.1021/acs.jcim.6b00136
   PubMed Web of Science ®Google Scholar
• Cosconati, S., Forli, S., Perryman, A. L., Harris, R., Goodsell, D. S., & Olson, A. J. (2010). Virtual screening with AutoDock: Theory and practice. Expert Opinion on Drug Discovery, 5(6), 597–607. https://doi.org/10.1517/17460441.2010.484460
   PubMed Web of Science ®Google Scholar
• Daina, A., Michielin, O., & Zoete, V. (2017). SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7(1), 42717. https://doi.org/10.1038/srep42717
   PubMed Web of Science ®Google Scholar
• Dallakyan, S., & Olson, A. J. (2015). Small-molecule library screening by docking with PyRx. Methods in Molecular Biology (Clifton, N.J.), 1263, 243–250. https://doi.org/10.1007/978-1-4939-2269-7_19
   PubMedGoogle Scholar
• Danielson, M. L., Hu, B., Shen, J., & Desai, P. V. (2017). In silico ADME techniques used in early-phase drug discovery. AAPS Advances in the Pharmaceutical Sciences Series, 25, 81–117. https://doi.org/10.1007/978-3-319-50042-3_4
   Google Scholar
• Daoud, N. E.-H., Borah, P., Deb, P. K., Venugopala, K. N., Hourani, W., Alzweiri, M., Bardaweel, S. K., & Tiwari, V. (2021). ADMET profiling in drug discovery and development: Perspectives of in silico, in vitro and integrated approaches. Current Drug Metabolism, 22(7), 503–522. https://doi.org/10.2174/1389200222666210705122913
   PubMed Web of Science ®Google Scholar
• Dearden, J. C. (2003). In silico prediction of drug toxicity. Journal of Computer-Aided Molecular Design, 17(2–4), 119–127. https://doi.org/10.1023/A:1025361621494
   PubMed Web of Science ®Google Scholar
• Efferth, T. (2017). Cancer combination therapy of the sesquiterpenoid artesunate and the selective EGFR-tyrosine kinase inhibitor erlotinib. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology, 37, 58–61. https://doi.org/10.1016/j.phymed.2017.11.003
   PubMed Web of Science ®Google Scholar
• Engel, J., Becker, C., Lategahn, J., Keul, M., Ketzer, J., Mühlenberg, T., Kollipara, L., Schultz-Fademrecht, C., Zahedi, R. P., Bauer, S., & Rauh, D. (2016). Insight into the inhibition of drug-resistant mutants of the receptor tyrosine kinase EGFR. Angewandte Chemie (International ed. in English), 55(36), 10909–10912. https://doi.org/10.1002/anie.201605011
   PubMed Web of Science ®Google Scholar
• Feng, L. S., Su, W. Q., Cheng, J. B., Xiao, T., Li, H. Z., Chen, D. A., & Zhang, Z. L. (2022). Benzimidazole hybrids as anticancer drugs: An updated review on anticancer properties, structure–activity relationship, and mechanisms of action (2019–2021). Archiv Der Pharmazie, 355(6), e2200051. https://doi.org/10.1002/ardp.202200051
   PubMed Web of Science ®Google Scholar
• Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., Scalmani, G., Barone, V., Mennucci, B., & Petersson, G. A. (2009). Gaussian 09, Revis. B. 01, Gaussian. Inc., Wallingford CT, 1–20. https://gaussian.com/glossary/g09/
   Google Scholar
• Gabrielson, E., & Hopkins, J. (2006). Worldwide trends in lung cancer pathology. Respirology (Carlton, Vic.), 11(5), 533–538. https://doi.org/10.1111/J.1440-1843.2006.00909.X
   PubMed Web of Science ®Google Scholar
• Hopkins, A. L., Keserü, G. M., Leeson, P. D., Rees, D. C., & Reynolds, C. H. (2014). The role of ligand efficiency metrics in drug discovery. Nature Reviews. Drug Discovery, 13(2), 105–121. https://doi.org/10.1038/nrd4163
   PubMed Web of Science ®Google Scholar
• Hu, S., Xie, G., Zhang, D. X., Davis, C., Long, W., Hu, Y., Wang, F., Kang, X., Tan, F., Ding, L., & Wang, Y. (2012). Synthesis and biological evaluation of crown ether fused quinazoline analogues as potent EGFR inhibitors. Bioorganic & Medicinal Chemistry Letters, 22(19), 6301–6305. https://doi.org/10.1016/j.bmcl.2012.06.067
   PubMed Web of Science ®Google Scholar
• Hu, Y., Zhou, L., Zhu, X., Dai, D., Bao, Y., & Qiu, Y. (2019). Pharmacophore modeling, multiple docking, and molecular dynamics studies on Wee1 kinase inhibitors. Journal of Biomolecular Structure & Dynamics, 37(10), 2703–2715. https://doi.org/10.1080/07391102.2018.1495576
   PubMed Web of Science ®Google Scholar
• Jacobson, M. P., Pincus, D. L., Rapp, C. S., Day, T. J. F., Honig, B., Shaw, D. E., & Friesner, R. A. (2004). A hierarchical approach to all-atom protein loop prediction. Proteins, 55(2), 351–367. https://doi.org/10.1002/PROT.10613
   PubMed Web of Science ®Google Scholar
• Jawad, B., Adhikari, P., Podgornik, R., & Ching, W.-Y. (2021). Key interacting residues between RBD of SARS-CoV-2 and ACE2 receptor: Combination of molecular dynamics simulation and density functional calculation. Journal of Chemical Information and Modeling, 61(9), 4425–4441. https://doi.org/10.1021/acs.jcim.1c00560
   PubMed Web of Science ®Google Scholar
• Jia, C. Y., Li, J. Y., Hao, G. F., & Yang, G. F. (2020). A drug-likeness toolbox facilitates ADMET study in drug discovery. Drug Discovery Today, 25(1), 248–258. https://doi.org/10.1016/J.DRUDIS.2019.10.014
   PubMed Web of Science ®Google Scholar
• Johnson, M., Garassino, M. C., Mok, T., & Mitsudomi, T. (2022). Treatment strategies and outcomes for patients with EGFR-mutant non-small cell lung cancer resistant to EGFR tyrosine kinase inhibitors: Focus on novel therapies. Lung Cancer (Amsterdam, Netherlands), 170, 41–51. https://doi.org/10.1016/j.lungcan.2022.05.011
   PubMed Web of Science ®Google Scholar
• Khuder, S. A., & Mutgi, A. B. (2001). Effect of smoking cessation on major histologic types of lung cancer. Chest, 120(5), 1577–1583. https://doi.org/10.1378/CHEST.120.5.1577
   PubMed Web of Science ®Google Scholar
• Kiran, A., Ali, U., Hussain, A., Ahmad, H. M. R., Abbas, F., Memon, T. A., & Hussain, A. (2021). Molecular designing of tetra-aryl-p-benzoquinones derivatives toward strong optical properties. Chemical Papers, 75(12), 6661–6671. https://doi.org/10.1007/s11696-021-01834-1
   Web of Science ®Google Scholar
• Kontoyianni, M. (2017). Docking and virtual screening in drug discovery. Methods in Molecular Biology (Clifton, N.J.), 1647, 255–266. https://doi.org/10.1007/978-1-4939-7201-2_18
   PubMedGoogle Scholar
• Kosaka, T., Yatabe, Y., Endoh, H., Kuwano, H., Takahashi, T., & Mitsudomi, T. (2004). Mutations of the epidermal growth factor receptor gene in lung cancer biological and clinical implications. Cancer Research, 64(24), 8919–8923. https://doi.org/10.1158/0008-5472.CAN-04-2818
   PubMed Web of Science ®Google Scholar
• Kumar, S., Abbas, F., Ali, I., Gupta, M. K., Kumar, S., Garg, M., & Kumar, D. (2023). Integrated network pharmacology and in-silico approaches to decipher the pharmacological mechanism of Selaginella tamariscina in the treatment of non-small cell lung cancer. Phytomedicine Plus, 3(2), 100419. https://doi.org/10.1016/j.phyplu.2023.100419
   Google Scholar
• Kumar, S., Ali, I., Abbas, F., Khan, N., Gupta, M. K., Garg, M., Kumar, S., & Kumar, D. (2023). In-silico identification of small molecule benzofuran-1,2,3-triazole hybrids as potential inhibitors targeting EGFR in lung cancer via ligand-based pharmacophore modeling and molecular docking studies. In Silico Pharmacology, 11(1), 20. https://doi.org/10.1007/s40203-023-00157-1
   PubMedGoogle Scholar
• Kumar, S., Sharma, A. K., Lalhlenmawia, H., & Kumar, D. (2021). Natural compounds targeting major signaling pathways in lung cancer. In Targeting Cellular Signalling Pathways in Lung Diseases (pp. 821–846). https://doi.org/10.1007/978-981-33-6827-9_37
   Google Scholar
• Kurter, H., Mert-Ozupek, N., Ellidokuz, H., & Calibasi-Kocal, G. (2022). In-silico drug-likeness analysis, ADME properties, and molecular docking studies of cyanidin-3-arabinoside, pelargonidin-3-glucoside, and peonidin-3-arabinoside as natural anticancer compounds against acting receptor-like kinase 5 receptor. Anti-Cancer Drugs, 33(6), 517–522. https://doi.org/10.1097/CAD.0000000000001297
   PubMed Web of Science ®Google Scholar
• Law, C. S. W., & Yeong, K. Y. (2021). Benzimidazoles in drug discovery: A patent review. ChemMedChem, 16(12), 1861–1877. https://doi.org/10.1002/CMDC.202100004
   PubMed Web of Science ®Google Scholar
• Lemjabbar-Alaoui, H., Hassan, O. U. I., Yang, Y. W., & Buchanan, P. (2015). Lung cancer: Biology and treatment options. Biochimica et Biophysica Acta, 1856(2), 189–210. https://doi.org/10.1016/J.BBCAN.2015.08.002
   PubMed Web of Science ®Google Scholar
• Li, B. H., Ge, J. Q., Wang, Y. L., Wang, L. J., Zhang, Q., & Bian, C. (2021). Ligand-based and docking-based virtual screening of MDM2 inhibitors as potent anticancer agents. Computational and Mathematical Methods in Medicine, 2021, 3195957. https://doi.org/10.1155/2021/3195957
   PubMed Web of Science ®Google Scholar
• Liu, Q., Yu, S., Zhao, W., Qin, S., Chu, Q., & Wu, K. (2018). EGFR-TKIs resistance via EGFR-independent signaling pathways. Molecular Cancer, 17(1), 53. https://doi.org/10.1186/S12943-018-0793-1
   PubMedGoogle Scholar
• Maghraby, M. T. E., Salem, O. I. A., Youssif, B. G. M., & Sheha, M. M. (2023). Design, synthesis, and modelling study of new 1,2,3-triazole/chalcone hybrids with antiproliferative action as epidermal growth factor receptor inhibitors. Chemical Biology & Drug Design, 101(3), 749–759. https://doi.org/10.1111/cbdd.14178
   PubMed Web of Science ®Google Scholar
• Honório, K. M.,Moda, T. L., &Andricopulo, A. D. (2013). Pharmacokinetic properties and in silico ADME modeling in drug discovery. Medicinal Chemistry (Shariqah (United Arab Emirates)), 9(2), 163–176. 10.2174/1573406411309020002 23016542
   PubMed Web of Science ®Google Scholar
• Mignani, S., Rodrigues, J., Tomas, H., Jalal, R., Singh, P. P., Majoral, J. P., & Vishwakarma, R. A. (2018). Present drug-likeness filters in medicinal chemistry during the hit and lead optimization process: How far can they be simplified? Drug Discovery Today, 23(3), 605–615. https://doi.org/10.1016/j.drudis.2018.01.010
   PubMed Web of Science ®Google Scholar
• Moradi, M., Mousavi, A., Emamgholipour, Z., Giovannini, J., Moghimi, S., Peytam, F., Honarmand, A., Bach, S., & Foroumadi, A. (2023). Quinazoline-based VEGFR-2 inhibitors as potential anti-angiogenic agents: A contemporary perspective of SAR and molecular docking studies. European Journal of Medicinal Chemistry, 259, 115626. https://doi.org/10.1016/j.ejmech.2023.115626
   PubMed Web of Science ®Google Scholar
• Morris, G. M., Huey, R., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S., & Olson, A. J. (2009). AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. Journal of Computational Chemistry, 30(16), 2785–2791. https://doi.org/10.1002/JCC.21256
   PubMed Web of Science ®Google Scholar
• Nath, J., Paul, R., Ghosh, S. K., Paul, J., Singha, B., & Debnath, N. (2020). Drug repurposing and relabeling for cancer therapy: Emerging benzimidazole antihelminthics with potent anticancer effects. Life Sciences, 258, 118189. https://doi.org/10.1016/J.LFS.2020.118189
   PubMed Web of Science ®Google Scholar
• Nawareg, N. A., Mostafa, A. S., El-Messery, S. M., & Nasr, M. N. A. (2022). New benzimidazole based hybrids: Synthesis, molecular modeling study and anticancer evaluation as TopoII inhibitors. Bioorganic Chemistry, 127, 106038. https://doi.org/10.1016/j.bioorg.2022.106038
   PubMedGoogle Scholar
• O’Boyle, N. M., Banck, M., James, C. A., Morley, C., Vandermeersch, T., & Hutchison, G. R. (2011). Open Babel: An open chemical toolbox. Journal of Cheminformatics, 3(10), 33. https://doi.org/10.1186/1758-2946-3-33
   PubMed Web of Science ®Google Scholar
• Othman, D., I. A., Hamdi, A., Tawfik, S. S., Elgazar, A. A., & Mostafa, A. S. (2023). Identification of new benzimidazole-triazole hybrids as anticancer agents: Multi-target recognition, in vitro and in silico studies. Journal of Enzyme Inhibition and Medicinal Chemistry, 38(1), 2166037. https://doi.org/10.1080/14756366.2023.2166037
   PubMed Web of Science ®Google Scholar
• Pandi, S., Kulanthaivel, L., Subbaraj, G. K., Rajaram, S., & Subramanian, S. (2022). Screening of potential breast cancer inhibitors through molecular docking and molecular dynamics simulation. BioMed Research International, 2022, 3338549–3338549. https://doi.org/10.1155/2022/3338549
   PubMed Web of Science ®Google Scholar
• Panigrahi, D., Mishra, A., & Sahu, S. K. (2020). Pharmacophore modelling, QSAR study, molecular docking and insilico ADME prediction of 1,2,3-triazole and pyrazolopyridones as DprE1 inhibitor antitubercular agents. SN Applied Sciences, 2(5), 1–28. https://doi.org/10.1007/s42452-020-2638-y
   Web of Science ®Google Scholar
• Park, J. H., Liu, Y., Lemmon, M. A., & Radhakrishnan, R. (2012). Erlotinib binds both inactive and active conformations of the EGFR tyrosine kinase domain. Biochemical Journal, 448(3), 417–423. https://doi.org/10.1042/BJ20121513
   PubMed Web of Science ®Google Scholar
• Paul Gleeson, M., Hersey, A., & Hannongbua, S. (2011). In-silico ADME models: A general assessment of their utility in drug discovery applications. Current Topics in Medicinal Chemistry, 11(4), 358–381. https://doi.org/10.2174/156802611794480927
   PubMed Web of Science ®Google Scholar
• Peng, L., Song, Z. G., & Jiao, S. C. (2014). Efficacy analysis of tyrosine kinase inhibitors on rare non-small cell lung cancer patients harboring complex EGFR mutations. Scientific Reports, 4(1), 6104. https://doi.org/10.1038/SREP06104
   PubMedGoogle Scholar
• Perola, E. (2010). An analysis of the binding efficiencies of drugs and their leads in successful drug discovery programs. Journal of Medicinal Chemistry, 53(7), 2986–2997. https://doi.org/10.1021/jm100118x 20235539
   PubMed Web of Science ®Google Scholar
• Pinzi, L., & Rastelli, G. (2019). Molecular docking: Shifting paradigms in drug discovery. International Journal of Molecular Sciences, 20(18), 4331. https://doi.org/10.3390/IJMS20184331
   PubMed Web of Science ®Google Scholar
• Raies, A. B., & Bajic, V. B. (2016). In silico toxicology: Computational methods for the prediction of chemical toxicity. Wiley Interdisciplinary Reviews. Computational Molecular Science, 6(2), 147–172. https://doi.org/10.1002/WCMS.1240
   PubMed Web of Science ®Google Scholar
• Rasheed, M. A., Iqbal, M. N., Saddick, S., Ali, I., Khan, F. S., Kanwal, S., Ahmed, D., Ibrahim, M., Afzal, U., & Awais, M. (2021). Identification of lead compounds against SCM (Fms10) in enterococcus faecium using computer aided drug designing. Life (Basel, Switzerland), 11(2), 77. https://doi.org/10.3390/life11020077
   PubMed Web of Science ®Google Scholar
• Raymond, E., Faivre, S., & Armand, J. P. (2000). Epidermal growth factor receptor tyrosine kinase as a target for anticancer therapy. Drugs, 60(Supplement 1), 15–23. https://doi.org/10.2165/00003495-200060001-00002
   PubMedGoogle Scholar
• Russell, É., Conroy, M. J., & Barr, M. P. (2022). Harnessing natural killer cells in non-small cell lung cancer. Cells, 11(4), 605. https://doi.org/10.3390/CELLS11040605
   PubMed Web of Science ®Google Scholar
• Russo, T. V., Martin, R. L., & Hay, P. J. (1994). Density functional calculations on first‐row transition metals. Journal of Chemical Physics, 101(9), 7729–7737. https://doi.org/10.1063/1.468265
   Web of Science ®Google Scholar
• Safdar, A., Malathum, K., Rodriguez, S. J., Husni, R., & Rolston, K. V. I. (2004). Strongyloidiasis in patients at a comprehensive cancer center in the United States. Cancer, 100(7), 1531–1536. https://doi.org/10.1002/CNCR.20120
   PubMed Web of Science ®Google Scholar
• Sander, T., Freyss, J., von Korff, M., Reich, J. R., & Rufener, C. (2009). OSIRIS, an entirely in-house developed drug discovery informatics system. Journal of Chemical Information and Modeling, 49(2), 232–246. https://doi.org/10.1021/CI800305F
   PubMed Web of Science ®Google Scholar
• Sarna, L., Evangelista, L., Tashkin, D., Padilla, G., Holmes, C., Brecht, M. L., & Grannis, F. (2004). Impact of respiratory symptoms and pulmonary function on quality of life of long-term survivors of non-small cell lung cancer. Chest, 125(2), 439–445. https://doi.org/10.1378/CHEST.125.2.439
   PubMed Web of Science ®Google Scholar
• Satija, G., Sharma, B., Madan, A., Iqubal, A., Shaquiquzzaman, M., Akhter, M., Parvez, S., Khan, M. A., & Alam, M. M. (2022). Benzimidazole based derivatives as anticancer agents: Structure activity relationship analysis for various targets. Journal of Heterocyclic Chemistry, 59(1), 22–66. https://doi.org/10.1002/jhet.4355
   Web of Science ®Google Scholar
• Scagliotti, G. V., Selvaggi, G., Novello, S., & Hirsch, F. R. (2004). The biology of epidermal growth factor receptor in lung cancer. Clinical Cancer Research, 10(12), 4227s–4232s. https://doi.org/10.1158/1078-0432.CCR-040007
   PubMed Web of Science ®Google Scholar
• Sharma, A., Shambhwani, D., Pandey, S., Singh, J., Lalhlenmawia, H., Kumarasamy, M., Singh, S. K., Chellappan, D. K., Gupta, G., Prasher, P., Dua, K., & Kumar, D. (2023). Advances in lung cancer treatment using nanomedicines. ACS Omega, 8(1), 10–41. https://doi.org/10.1021/acsomega.2c04078
   PubMed Web of Science ®Google Scholar
• Singu, P. S., Chilakamarthi, U., Mahadik, N. S., Keerti, B., Valipenta, N., Mokale, S. N., Nagesh, N., & Kumbhare, R. M. (2021). Benzimidazole-1,2,3-triazole hybrid molecules: Synthesis and study of their interaction with G-quadruplex DNA. RSC Medicinal Chemistry, 12(3), 416–429. https://doi.org/10.1039/D0MD00414F
   PubMedGoogle Scholar
• Smits, A. J. J., Kummer, J. A., Hinrichs, J. W. J., Herder, G. J. M., Scheidel-Jacobse, K. C., Jiwa, N. M., Ruijter, T. E. G., Nooijen, P. T. G. A., Looijen-Salamon, M. G., Ligtenberg, M. J. L., Thunnissen, F. B., Heideman, D. A. M., de Weger, R. A., & Vink, A. (2012). EGFR and KRAS mutations in lung carcinomas in the Dutch population: Increased EGFR mutation frequency in malignant pleural effusion of lung adenocarcinoma. Cellular Oncology (Dordrecht), 35(3), 189–196. https://doi.org/10.1007/S13402-012-0078-4
   PubMed Web of Science ®Google Scholar
• Sridhar Goud, N., Pooladanda, V., Muni Chandra, K., Lakshmi Soukya, P. S., Alvala, R., Kumar, P., Nagaraj, C., Dawn Bharath, R., Qureshi, I. A., Godugu, C., & Alvala, M. (2020). Novel benzimidazole-triazole hybrids as apoptosis inducing agents in lung cancer: Design, synthesis, 18F-radiolabeling & galectin-1 inhibition studies. Bioorganic Chemistry, 102, 104125. https://doi.org/10.1016/j.bioorg.2020.104125
   PubMed Web of Science ®Google Scholar
• Stanzione, F., Giangreco, I., & Cole, J. C. (2021). Use of molecular docking computational tools in drug discovery. Progress in Medicinal Chemistry, 60, 273–343. https://doi.org/10.1016/BS.PMCH.2021.01.004
   PubMedGoogle Scholar
• Tannock, I. F. (1980). In vivo interaction of anti-cancer drugs with misonidazole or metronidazole: Methotrexate, 5-fluorouracil and adriamycin. British Journal of Cancer, 42(6), 871–880. https://doi.org/10.1038/bjc.1980.334
   PubMed Web of Science ®Google Scholar
• Terstappen, G. C., & Reggiani, A. (2001). In silico research in drug discovery. Trends in Pharmacological Sciences, 22(1), 23–26. https://doi.org/10.1016/S0165-6147(00)01584-4
   PubMed Web of Science ®Google Scholar
• Tian, S., Wang, J., Li, Y., Li, D., Xu, L., & Hou, T. (2015). The application of in silico drug-likeness predictions in pharmaceutical research. Advanced Drug Delivery Reviews, 86, 2–10. https://doi.org/10.1016/J.ADDR.2015.01.009
   PubMed Web of Science ®Google Scholar
• Troiani, T., Martinelli, E., Capasso, A., Morgillo, F., Orditura, M., De Vita, F., & Ciardiello, F. (2012). Targeting EGFR in pancreatic cancer treatment. Current Drug Targets, 13(6), 802–810. https://doi.org/10.2174/138945012800564158
   PubMed Web of Science ®Google Scholar
• Upadhyay, J., Gajjar, A., & Suhagia, B. N. (2019). Combined ligand-based and structure-based virtual screening approach for identification of new dipeptidyl peptidase 4 inhibitors. Current Drug Discovery Technologies, 16(4), 426–436. https://doi.org/10.2174/1570163815666180926111558
   PubMedGoogle Scholar
• Valerio, L. G. (2009). In silico toxicology for the pharmaceutical sciences. Toxicology and Applied Pharmacology, 241(3), 356–370. https://doi.org/10.1016/J.TAAP.2009.08.022
   PubMed Web of Science ®Google Scholar
• VLifeMDS. (2023). VLifeMDS molecular design suite from VLife Sciences Technologies Pvt. Ltd. SelectScience. https://www.selectscience.net/products/vlifemds-molecular-design-suite
   Google Scholar
• Wales, C. T. K., Taylor, F. R., Higa, A. T., McAllister, H. A., & Jacobs, A. T. (2015). ERK-dependent phosphorylation of HSF1 mediates chemotherapeutic resistance to benzimidazole carbamates in colorectal cancer cells. Anti-Cancer Drugs, 26(6), 657–666. https://doi.org/10.1097/CAD.0000000000000231
   PubMed Web of Science ®Google Scholar
• Wang, Y., Xing, J., Xu, Y., Zhou, N., Peng, J., Xiong, Z., Liu, X., Luo, X., Luo, C., Chen, K., Zheng, M., & Jiang, H. (2015). In silico ADME/T modelling for rational drug design. Quarterly Reviews of Biophysics, 48(4), 488–515. https://doi.org/10.1017/S0033583515000190
   PubMed Web of Science ®Google Scholar
• Xiong, G., Wu, Z., Yi, J., Fu, L., Yang, Z., Hsieh, C., Yin, M., Zeng, X., Wu, C., Lu, A., Chen, X., Hou, T., & Cao, D. (2021). ADMETlab 2.0: An integrated online platform for accurate and comprehensive predictions of ADMET properties. Nucleic Acids Research, 49(W1), W5–W14. https://doi.org/10.1093/NAR/GKAB255
   PubMed Web of Science ®Google Scholar
• Yang, Z., Hackshaw, A., Feng, Q., Fu, X., Zhang, Y., Mao, C., & Tang, J. (2017). Comparison of gefitinib, erlotinib and afatinib in non-small cell lung cancer: A meta-analysis. International Journal of Cancer, 140(12), 2805–2819. https://doi.org/10.1002/IJC.30691
   PubMed Web of Science ®Google Scholar
• Yin, X., Li, Y., Wang, H., Jia, T., Wang, E., Luo, Y., Wei, Y., Qin, Z., & Ma, X. (2022). Small cell lung cancer transformation: From pathogenesis to treatment. Seminars in Cancer Biology, 86(Pt 2), 595–606. https://doi.org/10.1016/J.SEMCANCER.2022.03.006
   PubMedGoogle Scholar
• Yu-Jing, Y. J.,Zhang, C. M., &Liu, Z. P. (2012). Recent developments of small molecule EGFR inhibitors based on the quinazoline core scaffolds. Anti-Cancer Agents in Medicinal Chemistry, 12(4), 391–406. http://dx.doi.org/10.2174/187152012800228652
   PubMed Web of Science ®Google Scholar
• Yun, C. H., Mengwasser, K. E., Toms, A. V., Woo, M. S., Greulich, H., Wong, K. K., Meyerson, M., & Eck, M. J. (2008). The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proceedings of the National Academy of Sciences of the United States of America, 105(6), 2070–2075. https://doi.org/10.1073/pnas.0709662105
   PubMed Web of Science ®Google Scholar
• Zhang, C., Zhong, B., Yang, S., Pan, L., Yu, S., Li, Z., Li, S., Su, B., & Meng, X. (2015). Synthesis and biological evaluation of thiabendazole derivatives as anti-angiogenesis and vascular disrupting agents. Bioorganic & Medicinal Chemistry, 23(13), 3774–3780. https://doi.org/10.1016/J.BMC.2015.03.085
   PubMed Web of Science ®Google Scholar
• Zhang, X., Perez-Sanchez, H., & Lightstone, F. C. (2017). A comprehensive docking and MM/GBSA rescoring study of ligand recognition upon binding antithrombin. Current Topics in Medicinal Chemistry, 17(14), 1631–1639. https://doi.org/10.2174/1568026616666161117112604
   PubMed Web of Science ®Google Scholar
• Zhao, L. Y., Xin, G. J., Tang, Y. Y., Li, X. F., Li, Y. Z., Tang, N., & Ma, Y. H. (2022). miR-664b-3p inhibits colon cell carcinoma via negatively regulating budding uninhibited by benzimidazole. Bioengineered, 13(3), 4857–4868. https://doi.org/10.1080/21655979.2022.2036400
   PubMed Web of Science ®Google Scholar