Targeting apoptosis; design, synthesis and biological evaluation of new benzoxazole and thiazole based derivatives
Abstract Several novel approaches to target Bcl-2 proteins and apoptotic pathways have been identified in recent years for the treatment of different types of cancer including colorectal cancer. However, no effective treatments were yet developed for colorectal cancer. Twenty two novel benzoxazole a...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | BMC Chemistry |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13065-023-01101-2 |
| _version_ | 1797363649343389696 |
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| author | Sama W. Helmy Mai I. Shahin Nermin Samir Deena S. Lasheen Dalal A. Abou El Ella |
| author_facet | Sama W. Helmy Mai I. Shahin Nermin Samir Deena S. Lasheen Dalal A. Abou El Ella |
| author_sort | Sama W. Helmy |
| collection | DOAJ |
| description | Abstract Several novel approaches to target Bcl-2 proteins and apoptotic pathways have been identified in recent years for the treatment of different types of cancer including colorectal cancer. However, no effective treatments were yet developed for colorectal cancer. Twenty two novel benzoxazole and thiazole−based compounds were designed, synthesized, and evaluated as potential Bcl-2 inhibitors with anti−proliferative activity. Compounds 8g, 12e and 13d showed good to moderate anti−proliferative activity against most of the NCI 60 cell line panel with mean growth inhibition percent of 45.13, 42.29 and 29.25%, respectively. They showed the greatest cell growth inhibition percent to HCT-116 cell line with the values of 68.0, 59.11 and 43.44%, respectively. The aforementioned compounds were furtherly investigated for their effect on HCT-116 cell cycle, and they showed increase in the total apoptosis with 17, 22, and 5%, respectively. Also, the apoptotic effect of compounds 8g, 12e and 13d, were tested by their effect on altering caspase-3 expression level in HCT-116 human cell line. The three compounds showed an increase in the caspase-3 levels by 6, 8 and 3 folds, respectively in comparison with the same untreated ones. Moreover, they were evaluated for their in–vitro Bcl-2 inhibitory activity and they showed percent inhibition of 60.2, 69.2 and 50.0%, respectively. Finally, the most potent compounds 8g and 12e showed 3.864 and 2.834 folds increase in Bax level compared to the control respectively. On the other hand, Bcl-2 was down−regulated to 0.31 and 0.415 folds compared to the control. The induction of apoptosis through increase in caspase 3 expression and down−regulation of Bcl-2 is the suggested mechanism of action. |
| first_indexed | 2024-03-08T16:24:06Z |
| format | Article |
| id | doaj.art-388da09d7a354eea83defb98401e2f6e |
| institution | Directory Open Access Journal |
| issn | 2661-801X |
| language | English |
| last_indexed | 2024-03-08T16:24:06Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Chemistry |
| spelling | doaj.art-388da09d7a354eea83defb98401e2f6e2024-01-07T12:06:58ZengBMCBMC Chemistry2661-801X2024-01-0118111810.1186/s13065-023-01101-2Targeting apoptosis; design, synthesis and biological evaluation of new benzoxazole and thiazole based derivativesSama W. Helmy0Mai I. Shahin1Nermin Samir2Deena S. Lasheen3Dalal A. Abou El Ella4Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams UniversityPharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams UniversityPharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams UniversityPharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams UniversityPharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams UniversityAbstract Several novel approaches to target Bcl-2 proteins and apoptotic pathways have been identified in recent years for the treatment of different types of cancer including colorectal cancer. However, no effective treatments were yet developed for colorectal cancer. Twenty two novel benzoxazole and thiazole−based compounds were designed, synthesized, and evaluated as potential Bcl-2 inhibitors with anti−proliferative activity. Compounds 8g, 12e and 13d showed good to moderate anti−proliferative activity against most of the NCI 60 cell line panel with mean growth inhibition percent of 45.13, 42.29 and 29.25%, respectively. They showed the greatest cell growth inhibition percent to HCT-116 cell line with the values of 68.0, 59.11 and 43.44%, respectively. The aforementioned compounds were furtherly investigated for their effect on HCT-116 cell cycle, and they showed increase in the total apoptosis with 17, 22, and 5%, respectively. Also, the apoptotic effect of compounds 8g, 12e and 13d, were tested by their effect on altering caspase-3 expression level in HCT-116 human cell line. The three compounds showed an increase in the caspase-3 levels by 6, 8 and 3 folds, respectively in comparison with the same untreated ones. Moreover, they were evaluated for their in–vitro Bcl-2 inhibitory activity and they showed percent inhibition of 60.2, 69.2 and 50.0%, respectively. Finally, the most potent compounds 8g and 12e showed 3.864 and 2.834 folds increase in Bax level compared to the control respectively. On the other hand, Bcl-2 was down−regulated to 0.31 and 0.415 folds compared to the control. The induction of apoptosis through increase in caspase 3 expression and down−regulation of Bcl-2 is the suggested mechanism of action.https://doi.org/10.1186/s13065-023-01101-2ApoptosisBcl-2CaspaseBenzoxazoleThiazoleColorectal cancer |
| spellingShingle | Sama W. Helmy Mai I. Shahin Nermin Samir Deena S. Lasheen Dalal A. Abou El Ella Targeting apoptosis; design, synthesis and biological evaluation of new benzoxazole and thiazole based derivatives BMC Chemistry Apoptosis Bcl-2 Caspase Benzoxazole Thiazole Colorectal cancer |
| title | Targeting apoptosis; design, synthesis and biological evaluation of new benzoxazole and thiazole based derivatives |
| title_full | Targeting apoptosis; design, synthesis and biological evaluation of new benzoxazole and thiazole based derivatives |
| title_fullStr | Targeting apoptosis; design, synthesis and biological evaluation of new benzoxazole and thiazole based derivatives |
| title_full_unstemmed | Targeting apoptosis; design, synthesis and biological evaluation of new benzoxazole and thiazole based derivatives |
| title_short | Targeting apoptosis; design, synthesis and biological evaluation of new benzoxazole and thiazole based derivatives |
| title_sort | targeting apoptosis design synthesis and biological evaluation of new benzoxazole and thiazole based derivatives |
| topic | Apoptosis Bcl-2 Caspase Benzoxazole Thiazole Colorectal cancer |
| url | https://doi.org/10.1186/s13065-023-01101-2 |
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