ABSTRACT
A pentaquinone based compound 3 has been synthesized which works as a selective and sensitive chemodosimeter for mercury ions via Hg(2+) promoted hydrolysis of an imine linkage to generate a fluorescent change in mixed aqueous media.
Subject(s)
Fluorescent Dyes/chemical synthesis , Mercury/chemistry , Schiff Bases/chemistry , Water/chemistry , Cell Line, Tumor , Fluorescent Dyes/chemistry , Fluorescent Dyes/metabolism , Humans , Hydrolysis , Mercury/metabolism , Molecular StructureABSTRACT
From an endophytic fungus, a close relative of Talaromyces sp., found in association with Cedrus deodara, four compounds including two new ones (2 and 4) were isolated and characterized. The structures of two compounds (1 and 4) were confirmed by X-ray crystallography. The compounds displayed a range of cytotoxicities against human cancer cell lines (HCT-116, A-549, HEP-1, THP-1, and PC-3). All the compounds were found to induce apoptosis in HL-60 cells, as evidenced by fluorescence and scanning electron microscopy studies. Also, the compounds caused significant microtubule inhibition in HL-60 cells.
Subject(s)
Ascomycota/chemistry , Bridged Bicyclo Compounds, Heterocyclic/isolation & purification , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Cedrus/microbiology , Isocoumarins/isolation & purification , Isocoumarins/pharmacology , Tubulin Modulators/isolation & purification , Tubulin Modulators/pharmacology , Apoptosis/drug effects , Bridged Bicyclo Compounds, Heterocyclic/chemistry , Crystallography, X-Ray , HCT116 Cells , HL-60 Cells , Humans , Isocoumarins/chemistry , Molecular Conformation , Molecular Structure , Tubulin Modulators/chemistryABSTRACT
1H-1,2,3-triazole tethered isatin conjugates have been synthesized and evaluated for cytotoxicity on four human cancer cell lines. The results revealed 5a, 5c, 5e and 5n proved to be twice as potent as 5-fluorouracil on THP-1 cell line with 5a and 5c being most active exhibiting IC(50) values of <1 against all cell lines except Caco-2. Activity profiles showed dependence on the substituents on isatin rings with a preference for hydrogen while a strong electron withdrawing fluoro as well as nitro substituents on either ring decreased the anticancer activity.
Subject(s)
Alkynes/chemistry , Azides/chemistry , Cycloaddition Reaction , Isatin/chemistry , Triazoles/chemical synthesis , Triazoles/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Humans , Triazoles/chemistryABSTRACT
In an attempt to discover a potent and selective anticancer agent, gallic acid has been modified to benzylidene indanones as tubulin polymerization inhibitors. These compounds were evaluated against several human cancer cell lines and also evaluated for inhibition of tubulin polymerase in in vitro assays. Three of the analogues exhibited strong cytotoxicity against human cancer cell lines IC(50)=10-880 nM and also showed tubulin polymerization inhibition (IC(50)=0.62-2.04 µM). Compound 9j, the best candidate of the series was found to be non-toxic in acute oral toxicity in Swiss-albino mice up to 1000 mg/kg dose.
Subject(s)
Antineoplastic Agents , Benzylidene Compounds/chemistry , Indans/chemical synthesis , Indans/pharmacology , Tubulin/chemistry , Administration, Oral , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Benzodioxoles , Benzylidene Compounds/chemical synthesis , Benzylidene Compounds/pharmacology , Binding Sites , Cell Line, Tumor , Cell Proliferation/drug effects , Computer Simulation , Humans , Indans/chemistry , Mice , Protein Structure, Tertiary , Tubulin/metabolism , Tubulin Modulators/chemical synthesis , Tubulin Modulators/chemistry , Tubulin Modulators/pharmacologyABSTRACT
New pentaquinone derivatives 5 and 8 having rhodamine moieties have been designed and synthesized that undergo through-bond energy transfer (TBET) in the presence of Hg(2+) ions among the various cations (Cu(2+), Pb(2+), Fe(2+), Fe(3+), Zn(2+), Ni(2+), Cd(2+), Co(2+), Ag(+), Ba(2+), Mg(2+), K(+), Na(+), and Li(+)) tested in mixed aqueous media.
Subject(s)
Biosensing Techniques/methods , Fluorescent Dyes/chemistry , Mercury/analysis , Quinones/chemistry , Rhodamines/chemistry , Cell Line, Tumor , Energy Transfer , Fluorescent Dyes/chemical synthesis , Humans , Quinones/chemical synthesis , Sensitivity and Specificity , Spectrometry, Fluorescence/methods , Spectrophotometry, UltravioletABSTRACT
Zinc ensemble of hexaphenylbenzene derivative 3 exhibits sensitive response toward adenosine monophosphate (AMP) and H(2)PO(4)(-) ions. Further, the application of derivative 3 as a multichannel molecular keypad could be realized in the presence of inputs of Zn(2+) ions, H(2)PO(4)(-) ions, and AMP.
Subject(s)
Adenosine Monophosphate/chemistry , Benzene/chemistry , Phosphoric Acids/chemistry , Zinc/chemistry , Biosensing Techniques , Ions/chemistry , Molecular StructureABSTRACT
A highly selective fluorescent chemodosimeter based on rhodamine is synthesized which undergoes Cu(2+) driven hydrolysis in aqueous media to produce fluorescence turn-on changes with a detection limit up to the nanomolar range.
Subject(s)
Copper/analysis , Fluorescent Dyes/analysis , Rhodamines/analysis , Catalysis , Cations/chemistry , Cell Line, Tumor , Copper/chemistry , Fluorescent Dyes/chemistry , Humans , Hydrolysis , Rhodamines/chemistryABSTRACT
A thiacalix[4]arene based fluorescent chemosensor 3 in the cone conformation has been synthesized and its recognition behaviour is evaluated toward various metal ions in mixed aqueous media. The chemosensor 3 showed high selectivity towards Fe(3+) ions by fluorescence quenching of excimer emission. Further, evaluation of the 3·Fe(3+) complex prepared in situ demonstrated great promise for the detection of the Fe(3+) ion in the presence of amino acids, blood serum and bovine serum albumin (BSA) solution. The compound 3 has suitable permeability into the PC3 cells and can be utilized as a Fe(3+) selective sensor in living cells (PC3 cells).
Subject(s)
Ferric Compounds/analysis , Fluorescent Dyes/chemical synthesis , Phenols/chemistry , Sulfides/chemistry , Animals , Cations , Cattle , Cell Line, Tumor , Ferric Compounds/blood , Fluorescent Dyes/chemistry , Humans , Molecular Structure , Serum Albumin, Bovine/chemistry , Spectrometry, FluorescenceABSTRACT
The manuscript describes the synthesis of novel 1,2,3-triazole tethered ß-lactam-chalcone bifunctional hybrids via click chemistry approach utilizing azide-alkyne cycloaddition reactions and their evaluation as anticancer agents against four human cancer cell lines. The presence of a cyclohexyl substituent at N-1 of ß-lactam ring and methoxy substituents, preferably ortho on ring A and para on ring B on chalcones markedly improved the anticancer profiles of the synthesized scaffolds with the most potent of the test compound exhibiting an IC(50) value of <1, 67.1, <1 and 6.37 µM against A-549(lung), PC-3(prostate), THP-1(leukemia), and Caco-2(colon) cell lines, respectively.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Chalcone/chemistry , Chalcone/pharmacology , Triazoles/chemistry , beta-Lactams/chemistry , Antineoplastic Agents/chemical synthesis , Cell Line, Tumor , Cell Proliferation/drug effects , Chalcone/chemical synthesis , Humans , Inhibitory Concentration 50ABSTRACT
A series of N-(2-anilino-pyridyl) linked 2-amino benzothiazoles (4a-n) and [1,2,4]triazolo [1,5-b]benzothiadiazine conjugates (5a-j) have been designed, synthesized and evaluated for their antiproliferative activity. Some of these compounds (4h-k, 4n, and 5e) have exhibited potent cytotoxicity specifically against human leukemia HL-60 cell lines with IC(50) values in the range of 0.08-0.70 µM. All these compounds were tested for their effects on the cell cycle perturbations and induction of apoptosis. Morphological evidences of apoptosis, including fragmentation of nuclei and inter nucleosomal DNA laddering formation were clearly observed after 24h exposure to compound 4i. Flow cytometry analysis revealed that compound 4i showed drastic cell cycle perturbations due to concentration dependant increase in the sub-G0 region which comprises of both the apoptotic and debris fraction, thus implying the extent of cell death. These compounds trigger the mitochondrial apoptotic pathway that results in the loss of mitochondrial membrane potential through activation of multiple caspases followed by activation of caspase-3, and finally cleavage of PARP. Further the mechanism of cell death was analysed by fluorescent microscopic analysis and also by scanning electron microscopy. The cytotoxicity of 4i correlated with induction of apoptosis, caspases activation and DNA damage and thus indicating the apoptotic pathway of anticancer effect of these compounds.
Subject(s)
Apoptosis/drug effects , Benzothiadiazines/pharmacology , Mitochondria/drug effects , Aniline Compounds/chemistry , Aniline Compounds/pharmacology , Animals , Benzothiadiazines/chemistry , Caspases/metabolism , Cell Cycle/drug effects , Cell Growth Processes/drug effects , Cell Line, Tumor , Drug Screening Assays, Antitumor , Growth Inhibitors/pharmacology , HL-60 Cells , Haplorhini , Humans , Nicotine/analogs & derivatives , Nicotine/chemistry , Nicotine/pharmacologyABSTRACT
An indole based "ratiometric" and "turn-off" tris(N-methylindolyl)methane based chemosensor depicting a contrasting fluorescent behavior towards Hg(2+) and Cu(2+) ions, exhibited NOR and YES logic functions, and also imaged intracellular Hg(2+) in cervix cancer (HeLa) cells.
Subject(s)
Copper/chemistry , Indoles/chemistry , Mercury/chemistry , Microscopy, Confocal , Coordination Complexes/chemistry , HeLa Cells , Humans , Ions/chemistry , Spectrometry, FluorescenceABSTRACT
Semi-synthetic analogues of ß-boswellic acid (BA) and 11-keto-ß-boswellic acid (KBA) were comparatively evaluated for in vitro cytotoxicity against human myeloid leukaemia (HL-60) and human cervical carcinoma (HeLa) cells. 2-Cyano analogues of both the triterpenes were observed to have significant cytotoxicity against both the cells, displaying cytotoxicity in HL-60 cells at low concentrations. Further investigations suggested the proapoptotic potential associated with the two molecules to induce cytotoxicity in HL-60 cells, where one of them showed early proapoptotic effect as evidenced by several biological end-points of the apoptosis such as annexinV binding, DNA fragmentation and increase in sub-G0 DNA fraction and apoptotic bodies formation (Hoechst 33258 staining and SEM studies).
Subject(s)
Apoptosis/drug effects , Nitriles/chemistry , Triterpenes/chemistry , Triterpenes/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Cycle/drug effects , HL-60 Cells , HeLa Cells , Humans , Oxygen/chemistryABSTRACT
A naphthalimide appended rhodamine based fluorescent chemosensor '1' is synthesized which undergoes through bond energy transfer in the presence of Hg(2+) ions in mixed aqueous media.
