Activation of lysosomal mediated cell death in the course of autophagy by mTORC1 inhibitor.

Lysosomal biogenesis plays a vital role in cell fate. Under certain conditions, excessive lysosomal biogenesis leads to susceptibility for lysosomal membrane permeabilization resulting in various pathological conditions including cell death. In cancer cells apoptosis machinery becomes dysregulated during the course of treatment, thus allows cancer cells to escape apoptosis.

Oxone-DMSO Triggered Methylene Insertion and C(sp)-C(sp)-H-C(sp) Bond Formation to Access Functional Bis-Heterocycles.

Metal-free insertion of a methylene group was achieved for the construction of a new C(sp)-C(sp)-H-C(sp) bond in order to prepare novel bis-heterocyclic scaffolds. The complete mechanistic investigations included experimental study and DFT calculations, and various symmetric and unsymmetric bis-pyrazoles as well as other pyrazole-based bis-heterocyclic molecules were prepared in moderate to high yields. Further modification of the bridged methylene group in the unsymmetric pyrazoles generated a chiral center to extend the scope of this method.

Direct N-heterocyclization of hydrazines to access styrylated pyrazoles: synthesis of 1,3,5-trisubstituted pyrazoles and dihydropyrazoles.

A microwave-assisted method has been developed for the synthesis of tri-substituted pyrazoles direct N-heterocyclization of hydrazines with metal-acetylacetonate and -dibenzylideneacetonate without using any base or additives. Most importantly, the synthesis of 1-aryl-5-phenyl-3-styryl-1-pyrazoles was achieved in a single step using hydrochloride salt of various phenylhydrazines and this is the first report for direct construction of these molecules. The reaction medium and microwave conditions play a critical role for their selective product formation during the reaction.

4-(N-Phenyl-N'-substituted benzenesulfonyl)-6-(4-hydroxyphenyl)quinolines as inhibitors of mammalian target of rapamycin.

A series of 4-(N-phenyl-N'-substituted benzenesulfonyl)-6-(4-hydroxyphenyl)quinolines was designed, synthesized and evaluated for their biological potential as anticancer agents by screening the molecules against panel of five human cancer cell lines viz. HL-60, MiaPaCa-2, HCT116, PC-3 and HEP-G2. The series has shown good mTOR inhibitory activity at 0.

DMSO/I2 mediated C-C bond cleavage of α-ketoaldehydes followed by C-O bond formation: a metal-free approach for one-pot esterification.

A novel and efficient I2/DMSO mediated metal-free strategy is presented for the direct C-C bond cleavage of aryl-/heteroaryl- or aliphatic α-ketoaldehydes by C2-decarbonylation and C1-carbonyl oxidation to give the corresponding carboxylic acids followed by esterification in one pot, offering excellent yields in both the steps. Here, DMSO acts as the oxygen source/oxidant and this reaction works very well under both conventional heating and microwave irradiation. This is a very simple and convenient protocol.

A Novel Quinoline Based Second-generation mTOR Inhibitor that Induces Apoptosis and Disrupts PI3K-Akt-mTOR Signaling in Human Leukemia HL-60 Cells.

Deregulation of the PI3K-Akt-mTOR pathway is unanimously pragmatic in a number of tumors. This pathway pedals proliferation, survival, translation, and coupled with tumor-associated endurance. Current efforts focus on the discovery and development of novel inhibitors of this pathway.

C-H oxygenation and N-trifluoroacylation of arylamines under metal-free conditions: a convenient approach to 2-aminophenols and N-trifluoroacyl-ortho-aminophenols.

Direct ortho-hydroxylation through C-H oxygenation and N-trifluoroacylation of anilines was achieved in a single step under metal-free conditions by using a combination of TFA and oxone. The method allowed the formation of functionalised amino phenolic compounds such as ortho-hydroxy-N-trifluoroacetanilides in good yields with broad substrate scope.