TY - JOUR
T1 - Synthesis, docking and ADMET studies of novel chalcone triazoles for anti-cancer and anti-diabetic activity
AU - Chinthala, Yakaiah
AU - Thakur, Sneha
AU - Tirunagari, Shalini
AU - Chinde, Srinivas
AU - Domatti, Anand Kumar
AU - Arigari, Niranjana Kumar
AU - Srinivas, K. V N S
AU - Alam, Sarfaraz
AU - Jonnala, Kotesh Kumar
AU - Khan, Feroz
AU - Tiwari, Ashok
AU - Grover, Paramjit
PY - 2015/3/26
Y1 - 2015/3/26
N2 - A series of novel chalcone-triazole derivatives were synthesized and screened for in vitro anticancer activity on the human cancer cell lines IMR32 (neuroblastoma), HepG2 (hepatoma) and MCF-7 (breast adenocarcinoma), DU-145 (prostate carcinoma), and A549 (lung adenocarcinoma). Among the tested compounds, 4r showed the most promising anticancer activity in all the cell lines whereas, compounds 4c (IC50 65.86 μM), 4e (IC50 66.28 μM), 4o (IC50 35.81 μM), 4q (IC50 50.82 μM) and 4s (IC50 48.63 μM) showed better activity than the standard doxorubicin (IC50 69.33 μM) in A549 cell line alone. Rat intestinal α-glucosidase inhibitory activity of the synthesized derivatives showed 4m (IC50 67.77 μM), 4p (IC50 74.94 in μM) and 4s (IC50 102.10 μM) as most active compared to others. The in silico docking of synthesized derivatives 4a-4t with DNA topoisomerase IIα revealed the LibDock score in the range of 71.2623-118.29 whereas, compounds 4h, 4m, 4p and 4s with docking target α-glucosidase were in the range of 100.372-107.784.
AB - A series of novel chalcone-triazole derivatives were synthesized and screened for in vitro anticancer activity on the human cancer cell lines IMR32 (neuroblastoma), HepG2 (hepatoma) and MCF-7 (breast adenocarcinoma), DU-145 (prostate carcinoma), and A549 (lung adenocarcinoma). Among the tested compounds, 4r showed the most promising anticancer activity in all the cell lines whereas, compounds 4c (IC50 65.86 μM), 4e (IC50 66.28 μM), 4o (IC50 35.81 μM), 4q (IC50 50.82 μM) and 4s (IC50 48.63 μM) showed better activity than the standard doxorubicin (IC50 69.33 μM) in A549 cell line alone. Rat intestinal α-glucosidase inhibitory activity of the synthesized derivatives showed 4m (IC50 67.77 μM), 4p (IC50 74.94 in μM) and 4s (IC50 102.10 μM) as most active compared to others. The in silico docking of synthesized derivatives 4a-4t with DNA topoisomerase IIα revealed the LibDock score in the range of 71.2623-118.29 whereas, compounds 4h, 4m, 4p and 4s with docking target α-glucosidase were in the range of 100.372-107.784.
KW - 1,2,3-Triazoles
KW - anticancer activity
KW - chromanochalcones
KW - molecular docking
KW - α-Glucosidase inhibition
UR - http://www.scopus.com/inward/record.url?scp=84923917311&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2015.02.027
DO - 10.1016/j.ejmech.2015.02.027
M3 - Article
C2 - 25743216
AN - SCOPUS:84923917311
SN - 0223-5234
VL - 93
SP - 564
EP - 573
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
ER -