{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["9(8)"],"submitter":["Abbade Y"],"pubmed_abstract":["A series of alkylsulfonyl 1<i>H</i>-benzo[<i>d</i>]imidazole derivatives were synthesized and evaluated for anticancer activity against human breast cancer cells, MCF-7 <i>in vitro</i>. The cytotoxic potential was determined using the xCELLigence real-time cell analysis, and expression levels of genes related to microtubule organization, tumor suppression, apoptosis, cell cycle, and proliferation were examined by quantitative real-time polymerase chain reaction. Molecular docking against Bcl-2 was carried out using AutoDock Vina, while ADME studies were performed to predict the physicochemical and drug-likeness properties of the synthesized compounds. The results revealed that compounds <b>23</b> and <b>27</b> were the most potent cytotoxic derivatives against MCF-7 cells. Gene expression analysis showed that BCL-2 was the most prominent gene studied. Treatment of MCF-7 cells with compounds <b>23</b> and <b>27</b> resulted in significant downregulation of the BCL-2 gene, with fold changes of 128 and 256, respectively. Docking analysis predicted a strong interaction between the compounds and the target protein. Interestingly, all of the compounds exhibit a higher binding affinity toward Bcl-2 than the standard drug (compound <b>27</b> vina score = -9.6 kcal/mol, vincristine = -6.7 kcal/mol). Molecular dynamics simulations of compounds <b>23</b> and <b>27</b> showed a permanent stabilization in the binding site of Bcl-2 for 200 ns. Based on Lipinski and Veber's filters, all synthesized compounds displayed drug-like characteristics. These findings suggest that compounds <b>23</b> and <b>27</b> were the most promising cytotoxic compounds and downregulated the expression of the BCL-2 gene. These derivatives could be further explored as potential candidates for the treatment of breast cancer."],"journal":["ACS omega"],"pagination":["9547-9563"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10905736"],"repository":["biostudies-literature"],"pubmed_title":["Synthesis, Anticancer Activity, and <i>In Silico</i> Modeling of Alkylsulfonyl Benzimidazole Derivatives: Unveiling Potent Bcl-2 Inhibitors for Breast Cancer."],"pmcid":["PMC10905736"],"pubmed_authors":["Kisla MM","Ates-Alagoz Z","Abbade Y","Dogan TS","Mutlu P","Hassan MA","Celik I"],"additional_accession":[]},"is_claimable":false,"name":"Synthesis, Anticancer Activity, and <i>In Silico</i> Modeling of Alkylsulfonyl Benzimidazole Derivatives: Unveiling Potent Bcl-2 Inhibitors for Breast Cancer.","description":"A series of alkylsulfonyl 1<i>H</i>-benzo[<i>d</i>]imidazole derivatives were synthesized and evaluated for anticancer activity against human breast cancer cells, MCF-7 <i>in vitro</i>. The cytotoxic potential was determined using the xCELLigence real-time cell analysis, and expression levels of genes related to microtubule organization, tumor suppression, apoptosis, cell cycle, and proliferation were examined by quantitative real-time polymerase chain reaction. Molecular docking against Bcl-2 was carried out using AutoDock Vina, while ADME studies were performed to predict the physicochemical and drug-likeness properties of the synthesized compounds. The results revealed that compounds <b>23</b> and <b>27</b> were the most potent cytotoxic derivatives against MCF-7 cells. Gene expression analysis showed that BCL-2 was the most prominent gene studied. Treatment of MCF-7 cells with compounds <b>23</b> and <b>27</b> resulted in significant downregulation of the BCL-2 gene, with fold changes of 128 and 256, respectively. Docking analysis predicted a strong interaction between the compounds and the target protein. Interestingly, all of the compounds exhibit a higher binding affinity toward Bcl-2 than the standard drug (compound <b>27</b> vina score = -9.6 kcal/mol, vincristine = -6.7 kcal/mol). Molecular dynamics simulations of compounds <b>23</b> and <b>27</b> showed a permanent stabilization in the binding site of Bcl-2 for 200 ns. Based on Lipinski and Veber's filters, all synthesized compounds displayed drug-like characteristics. These findings suggest that compounds <b>23</b> and <b>27</b> were the most promising cytotoxic compounds and downregulated the expression of the BCL-2 gene. These derivatives could be further explored as potential candidates for the treatment of breast cancer.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2026-06-02T02:19:20.303Z","creation":"2025-04-06T17:12:50.13Z"},"accession":"S-EPMC10905736","cross_references":{"pubmed":["38434899"],"doi":["10.1021/acsomega.3c09411"]}}