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New quinoxaline-2(1)-ones as potential VEGFR-2 inhibitors: design, synthesis, molecular docking, ADMET profile and anti-proliferative evaluations
Eleven new quinoxaline derivatives were designed and synthesized as modified VEGFR-2 inhibitors of our previous work. The synthesized compounds were tested against three human cancer cell lines (HepG-2, MCF-7 and HCT-116). Compounds 11g , 11e and 11c were the most potent members against the tested c...
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Published in: | New journal of chemistry 2021-09, Vol.45 (36), p.16949-16964 |
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Main Authors: | , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Eleven new quinoxaline derivatives were designed and synthesized as modified VEGFR-2 inhibitors of our previous work. The synthesized compounds were tested against three human cancer cell lines (HepG-2, MCF-7 and HCT-116). Compounds
11g
,
11e
and
11c
were the most potent members against the tested cells. Compound
11g
(IC
50
= 4.50, 2.40, and 5.90 μM) was the most potent member compared to doxorubicin (IC
50
= 8.29, 9.65, and 7.68 μM) and sorafenib (IC
50
= 7.33, 9.41, and 7.23 μM) against HepG-2 and HCT-116, and MCF-7 cell lines, respectively. Compound
11e
showed better anti-proliferative activities than doxorubicin and sorafenib with IC
50
values of 5.34, 4.19, and 6.06 μM, against HepG-2 and HCT-116 and MCF-7 cell lines, respectively. In addition, the most active anti-proliferative derivatives
11c
,
11e
,
11f
, and
11g
were selected to evaluate their inhibitory activities against VEGFR-2. The tested compounds displayed good inhibitory activity with IC
50
values ranging from 0.75 to 1.36 μM. Among them, compound
11g
was the most active member with an IC
50
value of 0.75 μM, compared to the reference drug; sorafenib (IC
50
= 1.29 μM). Moreover, docking studies revealed that the synthesized compounds have good binding patterns against the prospective molecular target; VEGFR-2. In addition,
in silico
, ADMET and toxicity studies showed a high level of drug likeness for the synthesized compounds.
Eleven new quinoxaline derivatives were designed and synthesized as modified VEGFR-2 inhibitors of our previous work. |
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ISSN: | 1144-0546 1369-9261 |
DOI: | 10.1039/d1nj02509k |