Synthesis, docking and ADMET studies of novel chalcone triazoles for anti-cancer and anti-diabetic activity.
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.
Natural Product Chemistry, CSIR-Central Institute of Medicinal and Aromatic Plants-Research Centre, Boduppal, Hyderabad 500092, India.
Yakaiah
Y
Chinthala
Natural Product Chemistry, CSIR-Central Institute of Medicinal and Aromatic Plants-Research Centre, Boduppal, Hyderabad 500092, India.
Sneha
S
Thakur
Natural Product Chemistry, CSIR-Central Institute of Medicinal and Aromatic Plants-Research Centre, Boduppal, Hyderabad 500092, India.
Shalini
S
Tirunagari
Toxicology Unit, Biology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
Srinivas
S
Chinde
Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
Anand Kumar
AK
Domatti
Natural Product Chemistry, CSIR-Central Institute of Medicinal and Aromatic Plants-Research Centre, Boduppal, Hyderabad 500092, India.
Niranjana Kumar
NK
Arigari
Natural Product Chemistry, CSIR-Central Institute of Medicinal and Aromatic Plants-Research Centre, Boduppal, Hyderabad 500092, India.
Srinivas
S
K V N S
Metabolic and Structural Biology Department, CSIR-CIMAP, Lucknow 226015, UP, India.
Sarfaraz
S
Alam
Natural Product Chemistry, CSIR-Central Institute of Medicinal and Aromatic Plants-Research Centre, Boduppal, Hyderabad 500092, India. Electronic address: koteshkumarj@yahoo.com.
Kotesh Kumar
KK
Jonnala
Metabolic and Structural Biology Department, CSIR-CIMAP, Lucknow 226015, UP, India.
Feroz
F
Khan
Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
Ashok
A
Tiwari
Toxicology Unit, Biology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
Paramjit
P
Grover
D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000378:metabolism; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002599:Chalcone / Q000737:chemistry*; D060326:Chemistry Techniques, Synthetic; D004250:DNA Topoisomerases, Type II / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors / Q000009:adverse effects / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D051381:Rats; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D014230:Triazoles / Q000009:adverse effects / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D000520:alpha-Glucosidases / Q000378:metabolism
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D014230:Triazoles; D002599:Chalcone; D000520:alpha-Glucosidases; D004250:DNA Topoisomerases, Type II
1,2,3-Triazoles; Anticancer activity; Chromanochalcones; Molecular docking; α-Glucosidase inhibition