In Silico and In Vitro Investigation of Cytotoxicity and Apoptosis of Acridine/Sulfonamide Hybrids Targeting Topoisomerases I and II
Background: Sulfonamide acridine derivatives have garnered significant attention from medicinal chemists due to their diverse range of biological activities. Methods: In this study, eleven compounds were synthesized according to the literature, and their impact on cell growth inhibition, induction o...
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2024-11-01
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| author | Mohamed Badr Elshaymaa I. Elmongy Doaa Elkhateeb Yasmine S. Moemen Ashraf Khalil Hadeer Ali Reem Binsuwaidan Feby Awadallah Ibrahim El Tantawy El Sayed |
| author_facet | Mohamed Badr Elshaymaa I. Elmongy Doaa Elkhateeb Yasmine S. Moemen Ashraf Khalil Hadeer Ali Reem Binsuwaidan Feby Awadallah Ibrahim El Tantawy El Sayed |
| author_sort | Mohamed Badr |
| collection | DOAJ |
| description | Background: Sulfonamide acridine derivatives have garnered significant attention from medicinal chemists due to their diverse range of biological activities. Methods: In this study, eleven compounds were synthesized according to the literature, and their impact on cell growth inhibition, induction of apoptosis, and cell cycle distribution were assessed in three different cell lines. Their inhibitory effects on the topoisomerase (Topo) I and II were investigated in vitro. Molecular docking studies were conducted to predict the binding affinities of these compounds for crystallized downloaded topoisomerases. Results: The compounds were examined in vitro for their anticancer activity against human hepatic (HepG2) colon (HCT-8) and breast (MCF-7) carcinoma cell lines. Compound <b>8b</b> was the most active against HepG2, HCT-116, and MCF-7 with IC<sub>50</sub> 14.51, 9.39, and 8.83 µM, respectively, compared to Doxorubicin as reference. In addition, it demonstrated the highest potency among the tested compounds against Topo-I, with an IC<sub>50</sub> value of 3.41 µg/mL compared to the control camptothecin (IC<sub>50</sub> of 1.46 μM). Compound <b>7c</b> displayed a significant inhibitory effect on Topo-II, with an IC<sub>50</sub> of 7.33 μM, compared to an IC<sub>50</sub> value of 6.49 μM via Doxorubicin, the control. Compounds <b>7c</b> and <b>8b</b> were assessed against topoisomerases showing induction of apoptosis and a reduction in the S phase of the cell cycle. Molecular docking demonstrated interaction with the active site as with those exhibited by the co-crystallized ligands of the crystallized proteins in both topoisomerases. Conclusion: Compounds <b>7c</b> and <b>8b</b> hold promise as potential anticancer drugs due to their anti-proliferative and proapoptotic effects, which are mediated by their action on the topoisomerase enzyme, particularly Topo II. |
| format | Article |
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| institution | Kabale University |
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| spelling | doaj-art-7dcd68c70b5c46ea90cbeca0010ed44e2024-11-26T18:17:21ZengMDPI AGPharmaceuticals1424-82472024-11-011711148710.3390/ph17111487In Silico and In Vitro Investigation of Cytotoxicity and Apoptosis of Acridine/Sulfonamide Hybrids Targeting Topoisomerases I and IIMohamed Badr0Elshaymaa I. Elmongy1Doaa Elkhateeb2Yasmine S. Moemen3Ashraf Khalil4Hadeer Ali5Reem Binsuwaidan6Feby Awadallah7Ibrahim El Tantawy El Sayed8Department of Biochemistry, Faculty of Pharmacy, Menoufia University, Shebin El-Kom 6131567, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Ain Helwan, Cairo P.O. Box 11795, EgyptChemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom 32511, EgyptClinical Pathology Department, National Liver Institute, Menoufia University, Shebin El-Kom 32511, EgyptDepartment of Clinical Biochemistry and Molecular Diagnostics, National Liver Institute, Menoufia University, Shebin El-Kom 32511, EgyptChemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom 32511, EgyptDepartment of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi ArabiaChemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom 32511, EgyptChemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom 32511, EgyptBackground: Sulfonamide acridine derivatives have garnered significant attention from medicinal chemists due to their diverse range of biological activities. Methods: In this study, eleven compounds were synthesized according to the literature, and their impact on cell growth inhibition, induction of apoptosis, and cell cycle distribution were assessed in three different cell lines. Their inhibitory effects on the topoisomerase (Topo) I and II were investigated in vitro. Molecular docking studies were conducted to predict the binding affinities of these compounds for crystallized downloaded topoisomerases. Results: The compounds were examined in vitro for their anticancer activity against human hepatic (HepG2) colon (HCT-8) and breast (MCF-7) carcinoma cell lines. Compound <b>8b</b> was the most active against HepG2, HCT-116, and MCF-7 with IC<sub>50</sub> 14.51, 9.39, and 8.83 µM, respectively, compared to Doxorubicin as reference. In addition, it demonstrated the highest potency among the tested compounds against Topo-I, with an IC<sub>50</sub> value of 3.41 µg/mL compared to the control camptothecin (IC<sub>50</sub> of 1.46 μM). Compound <b>7c</b> displayed a significant inhibitory effect on Topo-II, with an IC<sub>50</sub> of 7.33 μM, compared to an IC<sub>50</sub> value of 6.49 μM via Doxorubicin, the control. Compounds <b>7c</b> and <b>8b</b> were assessed against topoisomerases showing induction of apoptosis and a reduction in the S phase of the cell cycle. Molecular docking demonstrated interaction with the active site as with those exhibited by the co-crystallized ligands of the crystallized proteins in both topoisomerases. Conclusion: Compounds <b>7c</b> and <b>8b</b> hold promise as potential anticancer drugs due to their anti-proliferative and proapoptotic effects, which are mediated by their action on the topoisomerase enzyme, particularly Topo II.https://www.mdpi.com/1424-8247/17/11/1487acridinescytotoxicitytopoisomerasemolecular docking |
| spellingShingle | Mohamed Badr Elshaymaa I. Elmongy Doaa Elkhateeb Yasmine S. Moemen Ashraf Khalil Hadeer Ali Reem Binsuwaidan Feby Awadallah Ibrahim El Tantawy El Sayed In Silico and In Vitro Investigation of Cytotoxicity and Apoptosis of Acridine/Sulfonamide Hybrids Targeting Topoisomerases I and II Pharmaceuticals acridines cytotoxicity topoisomerase molecular docking |
| title | In Silico and In Vitro Investigation of Cytotoxicity and Apoptosis of Acridine/Sulfonamide Hybrids Targeting Topoisomerases I and II |
| title_full | In Silico and In Vitro Investigation of Cytotoxicity and Apoptosis of Acridine/Sulfonamide Hybrids Targeting Topoisomerases I and II |
| title_fullStr | In Silico and In Vitro Investigation of Cytotoxicity and Apoptosis of Acridine/Sulfonamide Hybrids Targeting Topoisomerases I and II |
| title_full_unstemmed | In Silico and In Vitro Investigation of Cytotoxicity and Apoptosis of Acridine/Sulfonamide Hybrids Targeting Topoisomerases I and II |
| title_short | In Silico and In Vitro Investigation of Cytotoxicity and Apoptosis of Acridine/Sulfonamide Hybrids Targeting Topoisomerases I and II |
| title_sort | in silico and in vitro investigation of cytotoxicity and apoptosis of acridine sulfonamide hybrids targeting topoisomerases i and ii |
| topic | acridines cytotoxicity topoisomerase molecular docking |
| url | https://www.mdpi.com/1424-8247/17/11/1487 |
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