Quinoline conjugated 2-azetidinone derivatives as prospective anti-breast cancer agents: In vitro antiproliferative and anti-EGFR activities, molecular docking and in-silico drug likeliness studies
Two series [1–8 (series-1) and 9–16 (series-2)] of quinoline conjugated 2-azetidinones were evaluated for their antiproliferative potential against breast cancer cell lines MCF7 and MDA-MB-231 respectively. All the compounds were more active towards against MCF7 than MDA-MB-231 cancer cell lines and...
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Springer
2022-05-01
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| Series: | Journal of Saudi Chemical Society |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1319610322000539 |
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| author | K. Govindarao N. Srinivasan R. Suresh R.K. Raheja Sivakumar Annadurai Richie R. Bhandare Afzal B. Shaik |
| author_facet | K. Govindarao N. Srinivasan R. Suresh R.K. Raheja Sivakumar Annadurai Richie R. Bhandare Afzal B. Shaik |
| author_sort | K. Govindarao |
| collection | DOAJ |
| description | Two series [1–8 (series-1) and 9–16 (series-2)] of quinoline conjugated 2-azetidinones were evaluated for their antiproliferative potential against breast cancer cell lines MCF7 and MDA-MB-231 respectively. All the compounds were more active towards against MCF7 than MDA-MB-231 cancer cell lines and few compounds activity was more than the standard erlotinib. For instance, the compound 16 of series-2 bearing electron withdrawing fluorine atom at the 6th position of quinoline ring showed promising activity with MIC values of 2.33 ± 0.19 µg/mL for MCF7 and 4.19 ± 0.22 µg/mL for MDA-MB-231 cells, respectively. In a similar way, the compounds 8 and 14 containing fluorine and chlorine substituents respectively, and located at position-6 of quinoline scaffold showed better activity than erlotinib. The ability of target compounds to inhibit EGFR tyrosine kinase, one of the key enzymes involved in breast carcinomas was evaluated by in vitro enzymatic assay and it was found that the compound 8 had close inhibitory activity to erlotinib with an %inhibition of 97.1 ± 0.08 at 10 µM. The compounds showed selective toxicity on the cancer cell lines as their IC50 values are high against the human normal liver cell line-LO2. Further, the docking studies of the promising compounds 8, 14 and 16 revealed the important molecular interactions with the EGFR kinase enzyme (PDB ID: 6S9B). The physicochemical and pharmacokinetic properties of the most active compounds were predicted using Swiss ADME and pkCSM tools respectively. The most promising compounds arisen from the present study can be considered as prospective lead molecules for anticancer activity against breast carcinoma. |
| format | Article |
| id | doaj-art-bcdeb3dc3818453fa831df1a813b1687 |
| institution | Kabale University |
| issn | 1319-6103 |
| language | English |
| publishDate | 2022-05-01 |
| publisher | Springer |
| record_format | Article |
| series | Journal of Saudi Chemical Society |
| spelling | doaj-art-bcdeb3dc3818453fa831df1a813b16872025-08-20T03:48:36ZengSpringerJournal of Saudi Chemical Society1319-61032022-05-0126310147110.1016/j.jscs.2022.101471Quinoline conjugated 2-azetidinone derivatives as prospective anti-breast cancer agents: In vitro antiproliferative and anti-EGFR activities, molecular docking and in-silico drug likeliness studiesK. Govindarao0N. Srinivasan1R. Suresh2R.K. Raheja3Sivakumar Annadurai4Richie R. Bhandare5Afzal B. Shaik6VJ's College of Pharmacy, Department of Pharmaceutical Chemistry, Diwancheruvu, Rajahmundry, Andhra Pradesh, India.; Corresponding authors.Department of Pharmacy, Faculty of Engineering and Technology, Annamalai University, Annamalai Nagar, Tamil Nadu, IndiaDepartment of Pharmacy, Faculty of Engineering and Technology, Annamalai University, Annamalai Nagar, Tamil Nadu, IndiaSVKM’s Dr. Bhanuben Nanavati College of Pharmacy, Mumbai, IndiaDepartment of Pharmacognosy, College of Pharmacy, King Khalid University, Abha 61421, Saudi ArabiaDepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Ajman University, P O Box 346, Ajman, United Arab Emirates; Center of Medical and Bio-allied Health Sciences Research, Ajman University, P O Box 346, Ajman, United Arab Emirates; Corresponding authors.Department of Pharmaceutical Chemistry, Vignan Pharmacy College, Vadlamudi, Andhra Pradesh, India; Corresponding authors.Two series [1–8 (series-1) and 9–16 (series-2)] of quinoline conjugated 2-azetidinones were evaluated for their antiproliferative potential against breast cancer cell lines MCF7 and MDA-MB-231 respectively. All the compounds were more active towards against MCF7 than MDA-MB-231 cancer cell lines and few compounds activity was more than the standard erlotinib. For instance, the compound 16 of series-2 bearing electron withdrawing fluorine atom at the 6th position of quinoline ring showed promising activity with MIC values of 2.33 ± 0.19 µg/mL for MCF7 and 4.19 ± 0.22 µg/mL for MDA-MB-231 cells, respectively. In a similar way, the compounds 8 and 14 containing fluorine and chlorine substituents respectively, and located at position-6 of quinoline scaffold showed better activity than erlotinib. The ability of target compounds to inhibit EGFR tyrosine kinase, one of the key enzymes involved in breast carcinomas was evaluated by in vitro enzymatic assay and it was found that the compound 8 had close inhibitory activity to erlotinib with an %inhibition of 97.1 ± 0.08 at 10 µM. The compounds showed selective toxicity on the cancer cell lines as their IC50 values are high against the human normal liver cell line-LO2. Further, the docking studies of the promising compounds 8, 14 and 16 revealed the important molecular interactions with the EGFR kinase enzyme (PDB ID: 6S9B). The physicochemical and pharmacokinetic properties of the most active compounds were predicted using Swiss ADME and pkCSM tools respectively. The most promising compounds arisen from the present study can be considered as prospective lead molecules for anticancer activity against breast carcinoma.http://www.sciencedirect.com/science/article/pii/S13196103220005392-AzetidinonesEGFR kinaseMCF-7MDA-MB-231Quinoline |
| spellingShingle | K. Govindarao N. Srinivasan R. Suresh R.K. Raheja Sivakumar Annadurai Richie R. Bhandare Afzal B. Shaik Quinoline conjugated 2-azetidinone derivatives as prospective anti-breast cancer agents: In vitro antiproliferative and anti-EGFR activities, molecular docking and in-silico drug likeliness studies Journal of Saudi Chemical Society 2-Azetidinones EGFR kinase MCF-7 MDA-MB-231 Quinoline |
| title | Quinoline conjugated 2-azetidinone derivatives as prospective anti-breast cancer agents: In vitro antiproliferative and anti-EGFR activities, molecular docking and in-silico drug likeliness studies |
| title_full | Quinoline conjugated 2-azetidinone derivatives as prospective anti-breast cancer agents: In vitro antiproliferative and anti-EGFR activities, molecular docking and in-silico drug likeliness studies |
| title_fullStr | Quinoline conjugated 2-azetidinone derivatives as prospective anti-breast cancer agents: In vitro antiproliferative and anti-EGFR activities, molecular docking and in-silico drug likeliness studies |
| title_full_unstemmed | Quinoline conjugated 2-azetidinone derivatives as prospective anti-breast cancer agents: In vitro antiproliferative and anti-EGFR activities, molecular docking and in-silico drug likeliness studies |
| title_short | Quinoline conjugated 2-azetidinone derivatives as prospective anti-breast cancer agents: In vitro antiproliferative and anti-EGFR activities, molecular docking and in-silico drug likeliness studies |
| title_sort | quinoline conjugated 2 azetidinone derivatives as prospective anti breast cancer agents in vitro antiproliferative and anti egfr activities molecular docking and in silico drug likeliness studies |
| topic | 2-Azetidinones EGFR kinase MCF-7 MDA-MB-231 Quinoline |
| url | http://www.sciencedirect.com/science/article/pii/S1319610322000539 |
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