ABSTRACT
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.
Subject(s)
Chalcone/chemistry , Molecular Docking Simulation , Triazoles/chemical synthesis , Triazoles/pharmacology , Animals , Antigens, Neoplasm/chemistry , Antigens, Neoplasm/metabolism , Antineoplastic Agents/adverse effects , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Chemistry Techniques, Synthetic , DNA Topoisomerases, Type II/chemistry , DNA Topoisomerases, Type II/metabolism , DNA-Binding Proteins/chemistry , DNA-Binding Proteins/metabolism , Glycoside Hydrolase Inhibitors/adverse effects , Glycoside Hydrolase Inhibitors/chemical synthesis , Glycoside Hydrolase Inhibitors/metabolism , Glycoside Hydrolase Inhibitors/pharmacology , Humans , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/chemical synthesis , Hypoglycemic Agents/metabolism , Hypoglycemic Agents/pharmacology , Protein Conformation , Rats , Structure-Activity Relationship , Tissue Distribution , Triazoles/adverse effects , Triazoles/metabolism , alpha-Glucosidases/metabolismABSTRACT
BACKGROUND: Ledebouria is a genus of deciduous or weakly evergreen bulbs in the Hyacinthaceae family. This is recognized as the first collection made of the new taxon Ledebouria hyderabadensis, exist in the Hyderabad city of Andhra Pradesh, India. OBJECTIVE: The goal of this work was to investigate the phytochemical constituents present in the new specifies and also to evaluate the cytotoxic properties of the extracts and pure compounds against human cancer cell lines. MATERIALS AND METHODS: The anticancer activity was evaluated in in vitro mode by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. RESULTS: Phytochemical investigation of underground bulbs of indigenous, rare, and recently identified herb L. hyderabadensis yielded a bioactive homoisoflavanone, Scillascillin 1. The structure of the compound was established on the basis of various nuclear magnetic resonance and mass spectral data. The compound Scillascillin was isolated for the first time from L. hyderabadensis. In vitro anticancer activity, performed using MTT assay, showed compound 1 as significantly active against human cancer cell lines MCF-7 (breast cancer) and DU-145 (prostate cancer) with inhibitory concentration (IC)50 values 9.59 and 11.32 µg/ml respectively when compared with herb methanol extract (IC50 values 36.21 and 44.86 µg/ml respectively).
ABSTRACT
A new series of thiazolidinedione derivatives were synthesized and evaluated for in vitro α-glucosidase inhibition and anticancer activities. Compounds 3d, 3e and 3j showed potential α-glucosidase inhibition with IC50 values ranging between 0.1 and 0.3 µg/ml whereas compounds 3i, 3j and 3k have showed better anticancer activity towards human cancer cell lines IMR-32 (neuroblastoma), Hep-G2 (hepatoma) and MCF-7 (breast). Molecular docking studies revealed compounds 3d, 3e and 3j are potent inhibitors of α-glucosidase and also showed compliance with standard parameters of drug likeness.
