A series of diindolylmethanes (5a-t) were designed, synthesized, and examined for their cytotoxicity against four human cancer cell lines like prostate (DU-145), lung (A549), breast (MCF-7) and cervical cancer (HeLa). These results revealed that among all the hybrids, two (5k and 5r) were identified and exhibited significant cytotoxic effect against A549 cancer cells with IC50 values of 1.65 +/- 0.3 and 1.80 +/- 0.8 mu M respectively. To investigate the reasons for the cytotoxic activity, the conventional biological assays were carried out with 5k and 5r on the A549 cancer cells. Both hybrids led to the arrest of A549 cell lines at the G2/M phase of the cell cycle and strongly induced apoptosis. Further the apoptotic effects of 5k and 5r were confirmed by ROS, annexin-V FITC, and mitochondrial membrane potential. Moreover, structure-activity relationships were elucidated with various substitutions on these hybrids.

AbstractFor example, knoevenagel condensation of indole‐3‐carbaldehyde with pyrazolone (II) provides coupling product (III) which shows antibacterial activity (MIC value 50 μg/ml).

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

2-Styryl quinolines (9a-l) have been synthesized regioselectively from 2-methyl-quinoline by using NaOAc in water acetic acid binary solvents and evaluated for their antibacterial activity against both Gram-positive and Gram-negative strains. Among these, the compounds 12 and 8 were found to be active against both bacterial strains. Compounds 9b, 9f, 9g, 9i, 9j and 9k were the most active among the series exhibiting MIC values ranging between 1.9 and 31.2 μg ml(-1) against different bacterial strains. Compounds 9j and 9k were found to be as potent as the standard drug ciprofloxacin against Micrococcus luteus, Klebsiella planticola and Staphylococcus aureus. In addition, the compounds showed bactericidal activity; compound 9j was found to be better than ciprofloxacin, with an MBC value of 0.9 μg ml(-1) against both M. luteus and K. planticola. The compounds also inhibited biofilm formation, and compound 9j was found to be equipotent to erythromycin against M. luteus and S. aureus MLS16. Further, theoretical studies such as those on druggable properties and PMI plot have been carried out.

Piperidinium acetate catalyzed, three-component cyclocondensation between aryl aldehydes (1), malononitrile (2) and cyclic-1,3-diketo compounds (3) in the eco-friendly and universal solvent water at room temperature for 0.5 h, resulted in the formation of tetrahydro[b] pyran derivatives (4). The formation of 4 could also be established in a step-wise fashion by isolating independently each of the intermediates benzylidine malononitrile 5 and benzylidine cyclohexane-1,3-dione 6 and treating them subsequently with 3 and 2, respectively to obtain benzopyrans 4. Mechanistic studies on the formation of 4 from 1, 2 and 3 are reported. Further, the synthesis of 4 could also be achieved in two variable but identical end-product giving tandem syntheses by treating 1 with 2 and then with 3 giving 4 or by treating 1 with 3 and then with 2 giving 4. All the products were suitably characterized using NMR, IR and Mass spectroscopy.

Cancer remains one of the major contributors to human mortality and a hazard to human growth. The search for a new treatment continues unabated. Aurora kinases play an important role in cell cycle, and thus a potential target for the treatment of cancer. In the present work, we aim to discover potential leads against aurora kinase using various rational methods of drug discovery. The available crystal complexes of AKs were analyzed for their interactions and quantified with glide-extra precision (XP) docking. About 20 crystal pdb were selected from the protein databank based on the resolution factor, R-factor and R-value. And after docking with the native ligands, the RMSD value was calculated, wherein the protein with the least RMSD was found to be 3UOK which was further used for our screening of small molecules from the in-house database by molecular docking. Fragments which were found to possess the best interactions were considered for the synthesis with characterization, and biological activity was carried out against breast cancer and colorectal cancer cell lines to assess the inhibitory capability of synthesized compounds. Molecule with the molecular id IS2 i.e. (3E)-3-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-2H chromene-2,4(3H)-dione was found to possess inhibitory activity with an IC50 of 1.324 nM and 5.785 µM for breast cell line and colorectal cell line studies, respectively.

Knoevenagel condensation of isatin 1 with some nitriles 2 and with cyclohexane-1,3-diones 4 using piperidinium acetate as catalyst in water at 100°C results in the formation of α,β–unsaturated products, i.e. 2-(2-oxo-1,2-dihydro-indol-3ylidene)-malononitriles 3 and 5-dimethyl-2-(2-oxo-1,2-dihydro-indol-3-ylidine)cyclohexane-1,3-diones 5 respectively. The structures of products have been established by IR, H NMR and mass spectroscopy.

Each year, a huge number of new cases accounts of TB with added problems due to multidrug resistant TB varieties. Globally, TB is one of the top causes of loss of life among people living with HIV who are more likely than others to get TB infection. Current TB treatment includes long term administration of cocktail of drugs; hence, the development of an alternative armamentarium against TB is the primary requirement. In fact, new drugs with novel activity against mycobacteria are of significant importance in order to combat existing levels of resistance. The present report covers the discovery of a diarylquinoline TB drug, bedaquiline, its antituberculosis effects and mode of action. Clinical studies conducted on bedaquiline which brought it to the accelerated FDA acceptance have been described. This report is of great attention for therapeutic apothecaries working in TB medication growth in terms of creating further diarylquinoline applicants with a wide variety of antimycobacterial results.

A series of indolylidinepyrazolones were synthesized using a simple, green, and effective route and evaluated as anti-bacterial agents. The compounds were further studied via structure-guided docking study. One of the compounds exhibiting H-bonding interactions with conserved residue Arg144 turned out to be the most potent compound of the series. The minimum inhibitory concentration values ranged from 50 to 25μg/mL against Staphylococcus aureus in their anti microbial evaluation.

A simple and efficient synthesis of indolylidinethiazolidnediones (3) and indolylidinecyclic-1,3-diketones (5) has been developed by reaction of indole-3-aldehyde (1) with thiazolidinedione (2) or cyclic-1,3-diketones (4) using tetra butyl ammonium acetate (TBAA) melt as novel, cost-effective, and recyclable ionic liquid under solvent-free green conditions at 100 degrees C for 15-20min without additional use of catalyst. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications (R) for the following free supplemental resource(s): Full experimental and spectral details.]

AbstractAn efficient and environmentally benign protocol for the synthesis of thiazolylideneindoles (III), related cyclohexane (V) and barbituric acid derivatives (VII) is described.

A simple, efficient and green method for the synthesis of bisindolyloxindoles & bisazaindolyloxindoles (3, 5 & 7) under task- specific ionic liquid ([Bmim] OH) mediated and catalyzed conditions is described involving reaction of isatin 1 with indole 2 / azaindole 4 / pyrrole 6 at 100 degrees C in about an hr, giving the products in yields of 85-90%. This method is of significant value due to the eco- friendly nature of ionic liquid and non usage of separate catalyst to drive the reaction forward.

A simple, efficient and environmentally benign method for the one-pot, three component synthesis of spirooxindoles under task-specific novel ionic liquid Tetrabutylammonium acetate (TBA acetate) mediated and catalyzed conditions is described involving isatin 1, malononitrile 2 and cycli-1,3-diketone 3a-d / pyrazolone 3e compounds. This method is of significant value due to the eco-friendly and basic nature of ionic liquid there by eliminating usage of separate base catalyst to drive the reaction forward.

Tankyrase 1 and 2 belonging to the family of poly(ADP-ribosyl)ases play an important role in PARsylation by utilizing NAD+ as a substrate in order to generate ADP-ribose polymers. Tankyrases are involved in a number of cellular functions, that includes telomere homeostasis, mitotic spindle formation, vesicle transport linked to glucose metabolism, Wnt/beta-catenin signalling, and viral replication. These roles of tankyrases in disease-relevant cellular processes have made them attractive drug targets. Recently, several inhibitors have been identified as potential clinical leads. The current review covers the progress, mechanism and binding modes of recently known Tankyrase inhibitors and discusses the rational approaches that were used to identify the tankyrase inhibitors.

An efficient and environmentally benign method using Bu4NOAc as ionic liquid for the synthesis of the title compounds is presented.

A simple and efficient synthesis of pyran annulated heterocyclic compounds has been developed by reaction of aryl aldehydes, malanonitrile and cyclic-1,3-diketones using tetra butyl ammonium acetate (TBAA) melt as cost-effective and recyclable ionic liquid under solvent-free i.e green conditions at 100 degrees C for 10 minutes without additional use of catalyst.

Knoevenagel condensation between quinoline-2-aldehyde 1 and active methylene group containing 2,4-thiazolidinedione (TZD) 2 in PEG-600 at 100 degrees C for 2 hr, without the usage of any base, yields 5-quinolin-2-ylmethylene-thiazolidine-2,4-dione 3 which on alkylation gives N-substituted-5-quinolin-2-ylmethylene-thiazolidine-2,4-diones 5. Alternatively, 5 can also be synthesized by condensing N-substituted-thiazolidine-2,4-dione 4 with 1 in PEG-600 at 100 degrees C. It is possible to prepare 5 directly by condensing 2 with 1 followed by alkylation under one-pot conditions. The alpha,beta-unsaturated carbonyl derivatives 5, thus obtained, are subjected to C=C reduction using magnesium turnings in refluxing ethanol to obtain the corresponding reduced products 6 in high yields which are novel potential anti-hyperglycemic agents.

Symmetrically and unsymmetrically substituted title compounds are prepared under PTC conditions.

Knoevenagel condensation between indole-3-aldehyde 1 and an active methylene group containing 2,4-thiazolidinedione 2 in refluxing toluene using L-proline as a catalyst yielded 3, which on alkylation using 2 equivalents of alkylating agent under phase-transfer-catalyzed (PTC) conditions using K2CO3 as a base in dimethylformamide gave N,N-I-symmetrically disubstituted 5-(1H-indol-3ylmethylene)-thiazolidine-2,4-diones 4. Alternately, 4 can be synthesized by condensing 5 and 6 in a single step. Using this synthetic strategy, N,N-I-unsymmetricallydisubstituted derivatives 9a-f were prepared either by condensing 6 with N-substituted-2,4-thiazolidinedione 5 to obtain 7 followed by alkylation under PTC conditions or condensing 6 with N-unsubstituted-2,4-thiazolidinedione 2 to yield 8 followed by alkylation under PTC conditions. The latter are the dehydro analogs of the dihydro-N-substituted-5-(1H-indol-3-yl-methylene)-thiazolidine-2,4-diones, which are potential antihyperglycemic agents.