TY - JOUR
T1 - Benzoin schiff bases
T2 - Design, synthesis, and biological evaluation as potential antitumor agents
AU - Sabbah, Dima A.
AU - Al-Tarawneh, Fatima
AU - Talib, Wamidh H.
AU - Sweidan, Kamal
AU - Bardaweel, Sanaa K.
AU - Al-Shalabi, Eveen
AU - Zhong, Haizhen A.
AU - Sheikha, Ghassan Abu
AU - Khalaf, Reema Abu
AU - Mubarak, Mohammad S.
N1 - Funding Information:
This work was financially supported by the Deanship of Scientific Research and Graduate Studies at Al-Zaytoonah University of Jordan. Authors acknowledge the Deanship of Scientific Research at the University of Jordan. We are grateful to the Colleges of Pharmacy, the University of Jordan and Applied Science University for use of cell culture laboratory and equipment. This work was performed during Dr. Kamal's sabbatical leave at Al-Zaytoonah University of Jordan.
Publisher Copyright:
© 2018 Bentham Science Publishers.
PY - 2018
Y1 - 2018
N2 - Background: Phosphoinositide 3-kinase α (PI3Kα) is an attractive target for anticancer drug design. Objectives: Target compounds were designed to probe the significance of alcohol and imine moieties tailored on a benzoin scaffold to better understand the structure activity relation (SAR) and improve their biological activity as anticancer compounds. Methods: Chemical synthesis of the targeted compounds, biological evaluation tests against human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines, as well as Glide docking studies were employed in this investigation. Results: A new series of 1,2-diphenylimino ethanol was successfully synthesized and characterized by means of FT-IR, HRMS, NMR, and by elemental analysis. Biological screening revealed that the newly synthesized compounds inhibit PI3Kα activity in human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines. Results additionally showed that these compounds exhibit selective antiproliferative activity, induce apoptosis, and suppress the VEGF production. Compounds 2b, 2d, and 2g displayed promising inhibitory activity in HCT-116 suggesting that hydrophobic and/or hydrogen bond-acceptor mediate(s) ligand-receptor interaction on o-and m-positions. Furthermore, compounds 2g, 2i, 2j, and 2h, bearing hydrophobic moiety on m-and p-position, exerted high antiproliferative activity in T47D and MCF-7 cells, whereas compound 2e showed selectivity against T47D and MCF-7. Molecular docking studies against PI3Kα and caspase-3 demonstrated a strong correlation between the predicted binding affinity (∆Gobsd) and IC50 values of prepared compounds for the caspase-3 model, implying that the cellulous inhibitory activity was caspase-3-dependent. Moreover, Glide docking against PI3Kα identified Ser774, Lys802, E849, V851, and Asp933 as key binding residues. Conclusion: The series exerted a potential PI3Kα inhibitory activity in human carcinoma cell lines expressing PI3Kα.
AB - Background: Phosphoinositide 3-kinase α (PI3Kα) is an attractive target for anticancer drug design. Objectives: Target compounds were designed to probe the significance of alcohol and imine moieties tailored on a benzoin scaffold to better understand the structure activity relation (SAR) and improve their biological activity as anticancer compounds. Methods: Chemical synthesis of the targeted compounds, biological evaluation tests against human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines, as well as Glide docking studies were employed in this investigation. Results: A new series of 1,2-diphenylimino ethanol was successfully synthesized and characterized by means of FT-IR, HRMS, NMR, and by elemental analysis. Biological screening revealed that the newly synthesized compounds inhibit PI3Kα activity in human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines. Results additionally showed that these compounds exhibit selective antiproliferative activity, induce apoptosis, and suppress the VEGF production. Compounds 2b, 2d, and 2g displayed promising inhibitory activity in HCT-116 suggesting that hydrophobic and/or hydrogen bond-acceptor mediate(s) ligand-receptor interaction on o-and m-positions. Furthermore, compounds 2g, 2i, 2j, and 2h, bearing hydrophobic moiety on m-and p-position, exerted high antiproliferative activity in T47D and MCF-7 cells, whereas compound 2e showed selectivity against T47D and MCF-7. Molecular docking studies against PI3Kα and caspase-3 demonstrated a strong correlation between the predicted binding affinity (∆Gobsd) and IC50 values of prepared compounds for the caspase-3 model, implying that the cellulous inhibitory activity was caspase-3-dependent. Moreover, Glide docking against PI3Kα identified Ser774, Lys802, E849, V851, and Asp933 as key binding residues. Conclusion: The series exerted a potential PI3Kα inhibitory activity in human carcinoma cell lines expressing PI3Kα.
KW - 1,2-diphenylimino ethanol
KW - Angiogenesis
KW - Caspase-3
KW - Glide docking
KW - HCT-116
KW - MCF-7
KW - PI3Kα
KW - T47D
UR - http://www.scopus.com/inward/record.url?scp=85052870592&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85052870592&partnerID=8YFLogxK
U2 - 10.2174/1573406414666180412160142
DO - 10.2174/1573406414666180412160142
M3 - Article
C2 - 29651943
AN - SCOPUS:85052870592
SN - 1573-4064
VL - 14
SP - 695
EP - 708
JO - Medicinal Chemistry
JF - Medicinal Chemistry
IS - 7
ER -