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Article

Antiproliferative Efficacy of N-(3-chloro-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine, DW-8, in Colon Cancer Cells Is Mediated by Intrinsic Apoptosis

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Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Health Science Campus, 3000 Arlington Ave, Toledo, OH 43614, USA
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School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Bhopal 462033, India
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Department of Pharmacy, Indira Gandhi National Tribal University, Lalpur, Amarkantak 484887, India
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Center of Innovation and Translational Research, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune 411030, India
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Department of Pharmaceutical Sciences, College of Pharmacy, St. John’s University, Queens, NY 11439, USA
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Department Centre of Medical and Bio-allied Health Sciences Research (CMBHSR), Ajman University, Ajman P.O. Box 346, United Arab Emirates
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Department of Cancer Biology, College of Medicine and Life Sciences, The University of Toledo, Health Science Campus, 3000 Arlington Ave, Toledo, OH 43614, USA
*
Authors to whom correspondence should be addressed.
Academic Editors: Manoj K. Pandey and Jean-Yves Winum
Molecules 2021, 26(15), 4417; https://doi.org/10.3390/molecules26154417
Received: 17 May 2021 / Revised: 23 June 2021 / Accepted: 15 July 2021 / Published: 22 July 2021
(This article belongs to the Special Issue Advancement in Design and Synthesis of Novel Drug)
A novel series of 4-anilinoquinazoline analogues, DW (1–10), were evaluated for anticancer efficacy in human breast cancer (BT-20) and human colorectal cancer (CRC) cell lines (HCT116, HT29, and SW620). The compound, DW-8, had the highest anticancer efficacy and selectivity in the colorectal cancer cell lines, HCT116, HT29, and SW620, with IC50 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 IC50 of 14.05 ± 0.37 µM. The selectivity index of DW-8 was >2-fold in colon cancer cells incubated with vehicle. We further determined the mechanisms of cell death induced by DW-8 in SW620 CRC cancer cells. DW-8 (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 DW-8 may represent a suitable lead for developing novel compounds to treat CRC. View Full-Text
Keywords: colorectal cancer; cytotoxicity; 4-anilino-quinazoline; intrinsic apoptosis; anticancer compound colorectal cancer; cytotoxicity; 4-anilino-quinazoline; intrinsic apoptosis; anticancer compound
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MDPI and ACS Style

Neupane, R.; Malla, S.; Abou-Dahech, M.S.; Balaji, S.; Kumari, S.; Waiker, D.K.; Moorthy, N.S.H.N.; Trivedi, P.; Ashby, C.R., Jr.; Karthikeyan, C.; Tiwari, A.K. Antiproliferative Efficacy of N-(3-chloro-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine, DW-8, in Colon Cancer Cells Is Mediated by Intrinsic Apoptosis. Molecules 2021, 26, 4417. https://doi.org/10.3390/molecules26154417

AMA Style

Neupane R, Malla S, Abou-Dahech MS, Balaji S, Kumari S, Waiker DK, Moorthy NSHN, Trivedi P, Ashby CR Jr., Karthikeyan C, Tiwari AK. Antiproliferative Efficacy of N-(3-chloro-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine, DW-8, in Colon Cancer Cells Is Mediated by Intrinsic Apoptosis. Molecules. 2021; 26(15):4417. https://doi.org/10.3390/molecules26154417

Chicago/Turabian Style

Neupane, Rabin, Saloni Malla, Mariam S. Abou-Dahech, Swapnaa Balaji, Shikha Kumari, Digambar K. Waiker, N. S.H.N. Moorthy, Piyush Trivedi, Charles R. Ashby Jr., Chandrabose Karthikeyan, and Amit K. Tiwari 2021. "Antiproliferative Efficacy of N-(3-chloro-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine, DW-8, in Colon Cancer Cells Is Mediated by Intrinsic Apoptosis" Molecules 26, no. 15: 4417. https://doi.org/10.3390/molecules26154417

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