title: New (E)-1-alkyl-1H-benzo[d]imidazol-2-yl)methylene)indolin-2-ones: Synthesis, in vitro cytotoxicity evaluation and apoptosis inducing studies.
abstract: A new series of (E)-benzo[d]imidazol-2-yl)methylene)indolin-2-one derivatives has been synthesized and evaluated for their in vitro cytotoxic activity against a panel of selected human cancer cell lines of prostate (PC-3 and DU-145) and breast (BT-549, MDA-MB-231, MCF-7, 4T1), non-small lung (A549) and gastric (HGC) cancer cells along with normal breast epithelial cells (MCF10A). Among the tested compounds, 8l showed significant cytotoxic activity against MDA-MB-231 and 4T1 cancer cells with IC50 values of 3.26 ± 0.24 μM and 5.96 ± 0.67 μM respectively. The compounds 8f, 8i, 8l and 8o were also screened on normal human breast epithelial cells (MCF10A) and found to be safer with lesser cytotoxicity. The treatment of MDA-MB-231 cells with 8l led to inhibition of cell migration ability through disruption of F-actin protein assembly. The flow-cytometry analysis reveals that the cells arrested in G0/G1 phase of the cell cycle. Further, the compound 8l induced apoptosis of MDA-MB-231 cells was characterized by different staining techniques such as Acridine Orange/Ethidium Bromide (AO/EB), DAPI, annexin V-FITC/PI, Rhodamine-123 and MitoSOX red assay. Western blot studies demonstrated that the compound 8l treatment led to activation of caspase-3, increased expression of cleaved PARP, increased expression of pro-apoptotic Bax and decreased expression of anti-apoptotic Bcl-2 in MDA-MB-231 cancer cells.
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Sharma
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Thummuri
authors.affiliation: Centre for Advanced Materials & Industrial Chemistry (CAMIC), School of Science, RMIT University, GPO Box 2476, Melbourne 3001, Australia.
authors.forename: T Srinivasa
authors.initials: TS
authors.lastname: Reddy
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
authors.forename: Kishna Ram
authors.initials: KR
authors.lastname: Senwar
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
authors.forename: V G M
authors.initials: VGM
authors.lastname: Naidu
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
authors.forename: Gannoju
authors.initials: G
authors.lastname: Srinivasulu
authors.affiliation: Centre for Advanced Materials & Industrial Chemistry (CAMIC), School of Science, RMIT University, GPO Box 2476, Melbourne 3001, Australia.
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Bharghava
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India. Electronic address: shankar@niperhyd.ac.in.
authors.forename: Nagula
authors.initials: N
authors.lastname: Shankaraiah
mesh_terms: D000199:Actins / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects; D020836:Protein Structure, Quaternary; D013481:Superoxides / Q000378:metabolism
chemical_list: D000199:Actins; D000970:Antineoplastic Agents; D007211:Indoles; C456900:indolin-2-one; D013481:Superoxides
keywords: 3-Alkenyl-indolin-2-one; Anticancer; Apoptosis; Benzimidazole; Knoevenagel condensation