Antiproliferative Efficacy of <i>N</i>-(3-chloro-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine, DW-8, in Colon Cancer Cells Is Mediated by Intrinsic Apoptosis
A novel series of 4-anilinoquinazoline analogues, <b>DW (1–10)</b>, were evaluated for anticancer efficacy in human breast cancer (BT-20) and human colorectal cancer (CRC) cell lines (HCT116, HT29, and SW620). The compound, <b>DW-8</b>, had the highest anticancer efficacy and...
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MDPI AG
2021-07-01
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| Online Access: | https://www.mdpi.com/1420-3049/26/15/4417 |
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| author | Rabin Neupane Saloni Malla Mariam Sami Abou-Dahech Swapnaa Balaji Shikha Kumari Digambar Kumar Waiker N. S. Hari Narayana Moorthy Piyush Trivedi Charles R. Ashby Chandrabose Karthikeyan Amit K. Tiwari |
| author_facet | Rabin Neupane Saloni Malla Mariam Sami Abou-Dahech Swapnaa Balaji Shikha Kumari Digambar Kumar Waiker N. S. Hari Narayana Moorthy Piyush Trivedi Charles R. Ashby Chandrabose Karthikeyan Amit K. Tiwari |
| author_sort | Rabin Neupane |
| collection | DOAJ |
| description | A novel series of 4-anilinoquinazoline analogues, <b>DW (1–10)</b>, were evaluated for anticancer efficacy in human breast cancer (BT-20) and human colorectal cancer (CRC) cell lines (HCT116, HT29, and SW620). The compound, <b>DW-8</b>, had the highest anticancer efficacy and selectivity in the colorectal cancer cell lines, HCT116, HT29, and SW620, with IC<sub>50</sub> values of 8.50 ± 2.53 µM, 5.80 ± 0.92 µM, and 6.15 ± 0.37 µM, respectively, compared to the non-cancerous colon cell line, CRL1459, with an IC<sub>50</sub> of 14.05 ± 0.37 µM. The selectivity index of <b>DW-8</b> was >2-fold in colon cancer cells incubated with vehicle. We further determined the mechanisms of cell death induced by <b>DW-8</b> in SW620 CRC cancer cells. <b>DW-8</b> (10 and 30 µM) induced apoptosis by (1) producing cell cycle arrest at the G2 phase; (2) activating the intrinsic apoptotic pathway, as indicated by the activation of caspase-9 and the executioner caspases-3 and 7; (3) nuclear fragmentation and (4) increasing the levels of reactive oxygen species (ROS). Overall, our results suggest that <b>DW-8</b> may represent a suitable lead for developing novel compounds to treat CRC. |
| first_indexed | 2024-03-10T09:11:39Z |
| format | Article |
| id | doaj.art-f9d33cedefe2484cbf2ef8031dc8093b |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T09:11:39Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-f9d33cedefe2484cbf2ef8031dc8093b2023-11-22T05:57:47ZengMDPI AGMolecules1420-30492021-07-012615441710.3390/molecules26154417Antiproliferative Efficacy of <i>N</i>-(3-chloro-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine, DW-8, in Colon Cancer Cells Is Mediated by Intrinsic ApoptosisRabin Neupane0Saloni Malla1Mariam Sami Abou-Dahech2Swapnaa Balaji3Shikha Kumari4Digambar Kumar Waiker5N. S. Hari Narayana Moorthy6Piyush Trivedi7Charles R. Ashby8Chandrabose Karthikeyan9Amit K. Tiwari10Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Health Science Campus, 3000 Arlington Ave, Toledo, OH 43614, USADepartment of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Health Science Campus, 3000 Arlington Ave, Toledo, OH 43614, USADepartment of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Health Science Campus, 3000 Arlington Ave, Toledo, OH 43614, USADepartment of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Health Science Campus, 3000 Arlington Ave, Toledo, OH 43614, USADepartment of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Health Science Campus, 3000 Arlington Ave, Toledo, OH 43614, USASchool of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Bhopal 462033, IndiaDepartment of Pharmacy, Indira Gandhi National Tribal University, Lalpur, Amarkantak 484887, IndiaCenter of Innovation and Translational Research, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune 411030, IndiaDepartment of Pharmaceutical Sciences, College of Pharmacy, St. John’s University, Queens, NY 11439, USADepartment of Pharmacy, Indira Gandhi National Tribal University, Lalpur, Amarkantak 484887, IndiaDepartment of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Health Science Campus, 3000 Arlington Ave, Toledo, OH 43614, USAA novel series of 4-anilinoquinazoline analogues, <b>DW (1–10)</b>, were evaluated for anticancer efficacy in human breast cancer (BT-20) and human colorectal cancer (CRC) cell lines (HCT116, HT29, and SW620). The compound, <b>DW-8</b>, had the highest anticancer efficacy and selectivity in the colorectal cancer cell lines, HCT116, HT29, and SW620, with IC<sub>50</sub> values of 8.50 ± 2.53 µM, 5.80 ± 0.92 µM, and 6.15 ± 0.37 µM, respectively, compared to the non-cancerous colon cell line, CRL1459, with an IC<sub>50</sub> of 14.05 ± 0.37 µM. The selectivity index of <b>DW-8</b> was >2-fold in colon cancer cells incubated with vehicle. We further determined the mechanisms of cell death induced by <b>DW-8</b> in SW620 CRC cancer cells. <b>DW-8</b> (10 and 30 µM) induced apoptosis by (1) producing cell cycle arrest at the G2 phase; (2) activating the intrinsic apoptotic pathway, as indicated by the activation of caspase-9 and the executioner caspases-3 and 7; (3) nuclear fragmentation and (4) increasing the levels of reactive oxygen species (ROS). Overall, our results suggest that <b>DW-8</b> may represent a suitable lead for developing novel compounds to treat CRC.https://www.mdpi.com/1420-3049/26/15/4417colorectal cancercytotoxicity4-anilino-quinazolineintrinsic apoptosisanticancer compound |
| spellingShingle | Rabin Neupane Saloni Malla Mariam Sami Abou-Dahech Swapnaa Balaji Shikha Kumari Digambar Kumar Waiker N. S. Hari Narayana Moorthy Piyush Trivedi Charles R. Ashby Chandrabose Karthikeyan Amit K. Tiwari Antiproliferative Efficacy of <i>N</i>-(3-chloro-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine, DW-8, in Colon Cancer Cells Is Mediated by Intrinsic Apoptosis Molecules colorectal cancer cytotoxicity 4-anilino-quinazoline intrinsic apoptosis anticancer compound |
| title | Antiproliferative Efficacy of <i>N</i>-(3-chloro-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine, DW-8, in Colon Cancer Cells Is Mediated by Intrinsic Apoptosis |
| title_full | Antiproliferative Efficacy of <i>N</i>-(3-chloro-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine, DW-8, in Colon Cancer Cells Is Mediated by Intrinsic Apoptosis |
| title_fullStr | Antiproliferative Efficacy of <i>N</i>-(3-chloro-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine, DW-8, in Colon Cancer Cells Is Mediated by Intrinsic Apoptosis |
| title_full_unstemmed | Antiproliferative Efficacy of <i>N</i>-(3-chloro-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine, DW-8, in Colon Cancer Cells Is Mediated by Intrinsic Apoptosis |
| title_short | Antiproliferative Efficacy of <i>N</i>-(3-chloro-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine, DW-8, in Colon Cancer Cells Is Mediated by Intrinsic Apoptosis |
| title_sort | antiproliferative efficacy of i n i 3 chloro 4 fluorophenyl 6 7 dimethoxyquinazolin 4 amine dw 8 in colon cancer cells is mediated by intrinsic apoptosis |
| topic | colorectal cancer cytotoxicity 4-anilino-quinazoline intrinsic apoptosis anticancer compound |
| url | https://www.mdpi.com/1420-3049/26/15/4417 |
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