A facile and metal-free domino reaction of TsDAM and 2-alkenylarylaldehyde: An easy access to 8-hydroxy-2,8-dihydro indeno [2,1-c]pyrazoles.

An efficient straightforward metal free domino approach was developed for the synthesis of various 8-hydroxy-2,8-dihydroindeno[2,1-c]pyrazoles via [3 + 2] cycloaddition of substituted alkenes and TsDAM (TosylDiAzoMethane). The salient features of this protocol include high efficiency, mild reaction conditions, greener solvent, metal-free reaction, scalability and broad substrate scope along with high regioselectivity and yields.

Regioselective Ring Expansion of 3-Ylideneoxindoles with Tosyldiazomethane (TsDAM): A Metal-Free and Greener Approach for the Synthesis of Pyrazolo-[1,5-c]quinazolines.

An efficient, metal-free approach to access pyrazolo-[1,5-c]quinazolines with 3-ylideneoxindoles and tosyldiazomethane (TsDAM) under mild aqueous reaction conditions has been developed and the solvent involvement in the present reaction has also been explored for the first time. This greener approach involves 1,3-dipolar cycloaddition, regioselective ring expansion, followed by the elimination of tosyl group with aqueous base in a single operation, and the product can be isolated in high purity without column chromatographic separation. The method is also compatible with a large variety of functional groups, providing good to excellent yields in water, thus resulting in a decrease of environmental impact in the pharmaceutical industry.

Design and synthesis of ß-carboline linked aryl sulfonyl piperazine derivatives: DNA topoisomerase II inhibition with DNA binding and apoptosis inducing ability.

A series of new ß-carboline linked aryl sulfonyl piperazine congeners have been synthesized by coupling various ß-carboline acids with substituted aryl sulfonyl piperazines. Evaluation of their anticancer activity against a panel of human cancer cell lines such as colon (HT-29), breast (MDA-MB-231), bone osteosarcoma (MG-63), brain (U87 MG), prostate (PC- 3) and normal monkey kidney (Vero) cell line has been done. Among the series, compound 8ec and 8ed has shown most potent cytotoxicity with an IC50 values of 2.80 ± 0.10 µM and 0.59 ± 0.28 µM respectively against MG-63 cell line and also potent on other cell lines tested. Compounds 8ec and 8ed was found to inhibit Topo II that is confirmed by specific Topo II inhibition assay. DNA binding studies, cell cycle analysis, Annexin V study indicate that these compounds has potential anticancer activity. Molecular docking studies for compound 8ec and 8ed are incorporated to understand the nature of interaction with topoisomerase IIα and dsDNA.

Synthesis of new triazole fused imidazo[2,1-b]thiazole hybrids with emphasis on Staphylococcus aureus virulence factors.

A series of new triazole fused imidazo[2,1-b]thiazole hybrids (9a-u) were designed, synthesized and evaluated as antimicrobial agents. Compounds 9c, 9d, 9e, 9j and 9l showed promising broad spectrum antimicrobial activity. Further, compound 9c exhibited significant anti-biofilm activity with single and mixed biofilm disruption demonstrated by Field Emission Scanning Electron Microscope (FE-SEM). Furthermore, molecular docking studies revealed that they interact with the virulence factor, Staphylococcus aureus dehydrosqualene synthase (CrtM) (PDB ID: 2ZCS). Overall, the findings suggest compound 9c as potential lead for further development of novel antibacterial and anti-biofilm agents.

Synthesis and biological evaluation of new bisindole-imidazopyridine hybrids as apoptosis inducers.

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 ±â€¯0.3 and 1.80 ±â€¯0.8 µM 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.

Regioselective ring expansion followed by H-shift of 3-ylidene oxindoles: a convenient synthesis of N-substituted/un-substituted pyrrolo[2,3-c] quinolines and marinoquinolines.

Herein, we report a simple and metal-free protocol for the synthesis of 4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinolines. The present method under mild reaction conditions with wide functional group compatibility gives several unexplored N-substituted/unsubstituted 4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinolines and marinoquinolines in good to excellent yields. Mechanistic insights for the synthesis of N-substituted pyrroloquinolines reveal the ring expansion of 3-ylideneoxindoles and H-shift as the key steps.

Solvent-Controlled, Tunable Domino Reaction of 3-Ylideneoxindoles with in Situ-Generated α-Aryldiazomethanes: A Facile Access to 3-Spirocyclopropyl-2-oxindole and Pyrazoloquinazolinone Scaffolds.

A mild and efficient solvent-controlled, metal-free switchable 1,3-dipolar cycloaddition/ring contraction or ring expansion domino reaction of 3-ylideneoxindoles with in situ-generated α-aryldiazomethanes has been developed. This domino reaction provided a series of aryl-substituted 3-spirocyclopropyl-2-oxindoles and pyrazoloquinazolinones with excellent regio- and diastereoselectivity from common substrates under varying solvent conditions.

Regioselective Ring Expansion of Isatins with In Situ Generated α-Aryldiazomethanes: Direct Access to Viridicatin Alkaloids.

A novel efficient one-pot regioselective ring-expansion reaction of isatins with in situ generated α-aryl/heteroaryldiazomethanes for the construction of viridicatin alkaloids has been described under metal-free conditions. The utility of this protocol is further demonstrated in the synthesis of naturally occurring viridicatin, viridicatol, and substituted 3- O-methyl viridicatin and their scale up.

Synthesis and biological evaluation of curcumin inspired indole analogues as tubulin polymerization inhibitors.

In our endeavour towards the development of potent cytotoxic agents, a series of some new curcumin inspired indole analogues, in which indole and phenyl moieties are linked on either sides of 1,5-diaryl-1,4-pentadien-3-one system have been synthesized and characterized by spectral data. All the newly synthesized analogues were tested for their cytotoxic potential against a panel of eight cancer cell lines namely, lung (A549), breast (MDA-MB-231, BT549 and 4T1), prostate (PC-3, DU145), gastric (HGC-27) and cervical (HeLa). Notably, among all the compounds tested, compounds 11c, 11d and 11f showed potent growth inhibition on PC-3 and BT549 with IC50 values in the range of 3.12-6.34 µM and 4.69-8.72 µM respectively. The most active compound (11c) was also tested on RWPE-1 (normal prostate) cells and was found to be safe compared to the PC-3 cells. In tubulin polymerization assay, compounds 11c and 11f effectively inhibited microtubule assembly with IC50 values of 10.21 ± 0.10 and 8.83 ± 0.06 µM respectively. The results from molecular modelling studies revealed that these compounds bind at the colchicine binding site of the tubulin. Moreover, DAPI and acridine orange/ethidium bromide staining studies indicated that compounds 11c and 11f can induce apoptosis in PC-3 cells. Further flow-cytometry analysis revealed that compound 11c arrests PC-3 cells in G2/M phase of the cell cycle while compound 11f treatment resulted in moderate increase in the G2/M population. Additionally, the treatment by these compounds led to the impairment of mitochondrial membrane potential (DΨm) in PC-3 cells.

Aldehyde-Promoted One-Pot Regiospecific Synthesis of Acrylamides Using an in Situ Generated Molybdenum Tetracarbonyl Amine [Mo(CO)4(amine)2] Complex.

A novel complex system generated in situ from Mo(CO)6 and an amine is described for the regiospecific aminocarbonylation of various terminal alkynes. The Mo(CO)6-amine system played a dual role as complexing agent and as CO donor, thus making this process palladium-free.