Ramendra Pratap

New arylated benzo[h]quinolines induce anti-cancer activity by oxidative stress-mediated DNA damage

The anti-cancer activity of the benzo[h]quinolines was evaluated on cultured human skin cancer (G361), lung cancer (H460), breast cancer (MCF7) and colon cancer (HCT116) cell lines. The inhibitory effect of these compounds on the cell growth was determined by the MTT assay. The compounds 3e, 3f, 3h and 3j showed potential cytotoxicity against these human cancer cell lines. Effect of active compounds on DNA oxidation and expression of apoptosis related gene was studied. We also developed a quantitative method to measure the activity of cyclin-dependent kinases-2 (CDK2) by western blotting in the presence of active compound. In addition, molecular docking revealed that benzo[h]quinolines can correctly dock into the hydrophobic pocket of the targets receptor protein aromatase and CDK2, while their bioavailability/drug-likeness was predicted to be acceptable but requires future optimization. These findings reveal that benzo[h]quinolines act as anti-cancer agents by inducing oxidative stress-mediated DNA damage.

Microwave assisted base dependent regioselective synthesis of partially reduced chromenes, isochromenes and phenanthrenes.

We have reported a microwave assisted base directed regioselective synthesis of partially reduced chromenes, isochromenes and phenanthrenes. Functionalized 4-(piperidin-1-yl)-5,6-dihydro-2H-benzo[h]-chromen-2-one-3-carbonitriles have been used as precursors, which on reaction with functionalized acetophenones in the presence of KOH in DMF under microwave irradiation yield (Z)-2-(2-aryl-5,6-dihydro-4H-benzo[f]isochromen-4-ylidene)acetonitriles. The use of NaH in DMF provides 3-aryl-1-(piperidin-1-yl)-9,10-dihydro phenanthrene-2-carbonitriles in excellent yield regioselectively. The use of cyclohexanone as a nucleophile source yields (Z)-2-(3,4,7,8-tetrahydro-1H-naphtho[2,1-c]chromen-6(2H)-ylidene)acetonitriles. The structure and geometry of isochromene have been proved without any ambiguity by single crystal X-ray diffraction.

One pot synthesis of tetrasubstituted thiophenes: [3 + 2] annulation strategy

A simple, efficient and economical synthesis of dimethyl 3-amino-5-(2-oxo-2-arylethyl)thiophene-2,4-dicarboxylates has been reported by ring opening of methyl 3-amino-6-aryl-4-oxo-4H-thieno[3,2-c]pyran-2-carboxylates by alkoxide ions. Pyranothiophenes have been obtained by the reaction of methyl thioglycolate and 6-aryl-4-methylthio-2H-pyran-2-one-3-carbonitriles in the presence of triethylamine. A one-pot multicomponent protocol for the synthesis of tetrasubstituted thiophenes has been developed by reaction of 6-aryl-4-methylthio-2H-pyran-2-one-3-carbonitriles and methyl thioglycolate in the presence of sodium methoxide in excellent yields. The structure of the isolated compound was confirmed by single crystal X-ray diffraction and spectroscopic studies.

Metal-free synthesis of nitrile based partially reduced thia-and oxa-thia[5]helicenes: conformation and dynamics

An expeditious, metal free, simple and convenient synthesis of partially reduced thia[5]helicenes and oxa-thia[5]helicenes, appended with nitrile and amino functionalities such as 3-sec.amino-5,6-dihydro-2H-1-thia-dibenzo[c,g]phenanthrene-4-carbonitriles 7 and (Z)-2-(5,6-dihydrobenzo[f]thiochromeno[3,4-c]-3-(2H)-ylidene)acetonitriles 6 has been delineated through base-catalyzed ring transformation of 4-sec.amino-2-oxo-2,5-dihydrothiochromeno[4,3-b]pyran-3-carbonitriles 4 by 2-tetralones 5. The molecular structure of one of the partially reduced thia[5]helicenes has been determined by X-ray crystallographic analysis. In order to calculate the inversion barrier of the helimeric enantiomers P-7a and M-7a, the molecular geometries of both, the ground states and the transition states have been optimized by the density functional theory (DFT) using B3LYP/6-311G.** Based on these structures, helimerization barrier of 44.36 K cal mol−1 has been predicted using MP2/6-311G** single-point energy calculations.

Ab initio and experimental studies on structure and vibrational spectra of some partially reduced benzo[c]phenanthrenes

A systematic study has been conducted on the conformation, electronic structure and vibrational spectra of benzo[c]phenanthrene and some of its partially reduced derivatives by experimental infrared spectroscopic and quantum chemical techniques. Electrostatic potential surfaces have been mapped over the electron density isosurfaces to obtain information about the size, shape, charge density distribution and chemical reactivity of the molecules. Possibility of hydrogen-hydrogen bonding has been explored in all the molecules. Partial reduction of the aromatic rings in benzo[c]phenanthrene leads to considerable molecular distortion with the approximate mean angle between the terminal rings increasing from 27.3 degrees to 46.0 degrees . The distortion is unequally distributed near the aromatic and saturated rings; the latter absorbs most of strain due to flexibility of the rings. A complete vibrational analysis of the experimental infrared spectra has been reported on the basis of frequency and intensity of the vibrational bands and potential energy distribution over the internal coordinates and characteristic bands have been identified.

Substituent dependent tunable fluorescence in thieno[3,2-c]pyrans

A series of thieno[3,2-c]pyrans were designed and synthesized by L-proline catalyzed reaction of 6-aryl/5,6-diaryl-4-methylthio-2H-pyrane-2-one-3-carbonitriles or 4-(methylthio)-2-oxo-5,6-dihydro-2H-benzo[h]chromene-3-carbonitrile and methylthioglycolate in good yields. These thieno[3,2-c]pyrans exhibit substituent dependent fluorescence. The 6-aryl-thieno[3,2-c]pyrans 3a–3e exhibit high fluorescence quantum yields (95%) with large Stokes shifts, whereas the 6,7-di-substituted-thieno[3,2-c]pyrans 3f–3h show poor fluorescence in solution and exhibit an aggregation-induced emission (AIE). Interestingly, fused 6,7-di-substituted-thieno[3,2-c]pyran is highly fluorescent in the solution state, which reveals that restricted intramolecular rotation is the cause for AIE in 3f–3h.

A carbanion induced ring switching synthesis of spiranes: an unprecedented approach

An unique approach to the synthesis of heterocyclic spiranes through ring switching transformation of suitably functionalized 2H-pyran-2-ones, benzo[h]chromene and thiochromeno[4,3-b]pyrans has been developed. The spirane dimer 11d displayed interesting halogen-hydrogen bonding to generate an elliptical cavity and may be relevant to the generation of a host guest assembly for specific cations and also a low helimerization energy barrier of spirane 17a.

Precursor directed regioselective synthesis of partially reduced benzo[e]indene through oxidative cyclization and benzo[h]quinolines

We have reported a simple, unprecedented base promoted synthesis of 7-substituted-1-(2-cyano-phenyl/phenyl)-3-sec amino-4,5-dihydro-1H-benz[e]indene-1,2-dicarbonitriles by reaction of 2-oxo-4-sec amino-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles and 2-cyanomethyl-benzonitrile/phenyl-acetonitrile under basic conditions at 100 °C. This reaction involves ring opening of 2-oxo-4-sec amino-5,6-dihydro-2H-benzo[h]chromene-3-carbonitrile by a carbanion generated in situ from 2-cyanomethylbenzonitrile/phenyl-acetonitrile followed by oxidative cyclization to afford the desired product. Alternatively, reaction of 6-aryl-4-sec amino-2H-pyran-2-one-3-carbonitriles and 2-cyanomethyl-benzonitrile under basic conditions provides functionalized benzo[h]quinolines. The structure of the synthesized compound was confirmed by single crystal X-ray.

Bicyclic ketone mediated synthesis of oxygenated aromatic systems

A concise and efficient synthesis of various oxygenated, polycyclic aromatic systems has been delineated through base catalyzed ring transformation of 2-oxo-4-(piperidin-1-yl)-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles by bicyclic ketones, as a source of carbanions in excellent yields.

One-pot and step-wise synthesis of thieno[3,2-c]pyridin-4-ones

Both one pot and step wise synthesis of methyl 3,5-diaminothieno[3,2-c]pyridin-4-one-2-carboxylates 6 have been delineated by the reaction of 6-aryl-4-methylthio-2H-pyran-2-one-3-carbonitriles 3, methyl mercaptoacetate and hydrazine hydrate. During the stepwise synthesis, functionalized thieno[3,2-c]pyran-4-ones 4 were isolated and treated with hydrazine hydrate to afford the desired products. Analogously, condensation–cyclisation of 5 with hydrazine hydrate delivered identical products, thieno[3,2-c]pyridin-4-ones 6, in excellent yields. The structure of isolated product 6 was ascertained by spectroscopic and single crystal X-ray diffraction analyses.