TY - JOUR
T1 - Discovery of new 5-substituted-indole-2-carboxamides as dual epidermal growth factor receptor (EGFR)/cyclin dependent kinase-2 (CDK2) inhibitors with potent antiproliferative action
AU - Mohamed, Fatma A.M.
AU - Alakilli, Saleha Y.M.
AU - El Azab, Eman Fawzy
AU - Baawad, Faris A.M.
AU - Shaaban, Esraa Ibrahim A.
AU - Alrub, Heba Abu
AU - Hendawy, Omnia
AU - Gomaa, Hesham A.M.
AU - Bakr, Adel G.
AU - Abdelrahman, Mostafa H.
AU - Trembleau, Laurent
AU - Mohammed, Anber F.
AU - Youssif, Bahaa G.M.
N1 - Funding Information:
This work was funded by the Deanship of Scientific Research at Jouf University under grant No. (DSR-2021-01-03181).
PY - 2023/4/1
Y1 - 2023/4/1
N2 - A new series of 5-substituted-3-ethylindole-2-carboxamides 5a-k and 6a-c was designed and synthesised in an attempt to develop a dual targeted antiproliferative agent. Various spectroscopic methods of analysis were used to confirm the structures of the new compounds. The antiproliferative effect of compounds 5a-k and 6a-c against four cancer cell lines was investigated. Compounds 5a-k and 6a-c had significant antiproliferative activity against the four cancer cell lines tested, with mean GI50 values ranging from 37 nM to 193 nM. The most powerful derivatives were compounds 5g, 5i, and 5j, with GI50 values of 55 nM, 49 nM, and 37 nM, respectively, in comparison to the reference erlotinib, which had a GI50 of 33 nM. The four most potent compounds, 5c, 5g, 5i, and 5j, were then investigated for their efficacy as EGFR inhibitors, and the findings showed that the tested compounds inhibited EGFR with IC50 values ranging from 85 nM to 124 nM when compared to the reference erlotinib (IC50 = 80 nM). Moreover, compounds 5c and 5g inhibited CDK2 with IC50 values of 46 ± 05 nM and 33 ± 04 nM, respectively. The EGFR and CDK2 assays revealed that compounds 5i and 5j displayed potent antiproliferative activity and can be considered as potential dual EGFR and CDK2 inhibitors.
AB - A new series of 5-substituted-3-ethylindole-2-carboxamides 5a-k and 6a-c was designed and synthesised in an attempt to develop a dual targeted antiproliferative agent. Various spectroscopic methods of analysis were used to confirm the structures of the new compounds. The antiproliferative effect of compounds 5a-k and 6a-c against four cancer cell lines was investigated. Compounds 5a-k and 6a-c had significant antiproliferative activity against the four cancer cell lines tested, with mean GI50 values ranging from 37 nM to 193 nM. The most powerful derivatives were compounds 5g, 5i, and 5j, with GI50 values of 55 nM, 49 nM, and 37 nM, respectively, in comparison to the reference erlotinib, which had a GI50 of 33 nM. The four most potent compounds, 5c, 5g, 5i, and 5j, were then investigated for their efficacy as EGFR inhibitors, and the findings showed that the tested compounds inhibited EGFR with IC50 values ranging from 85 nM to 124 nM when compared to the reference erlotinib (IC50 = 80 nM). Moreover, compounds 5c and 5g inhibited CDK2 with IC50 values of 46 ± 05 nM and 33 ± 04 nM, respectively. The EGFR and CDK2 assays revealed that compounds 5i and 5j displayed potent antiproliferative activity and can be considered as potential dual EGFR and CDK2 inhibitors.
UR - http://www.scopus.com/inward/record.url?scp=85150844764&partnerID=8YFLogxK
U2 - 10.1039/d3md00038a
DO - 10.1039/d3md00038a
M3 - Article
AN - SCOPUS:85150844764
SN - 2632-8682
VL - 14
SP - 734
EP - 744
JO - RSC Medicinal Chemistry
JF - RSC Medicinal Chemistry
IS - 4
ER -
