Novel Sulforaphane Analog Disrupts Phosphatidylinositol-3-Kinase-Protein Kinase B Pathway and Inhibits Cancer Cell Progression via Reactive Oxygen Species-Mediated Caspase-Independent Apoptosis.

Sulforaphane, a naturally occurring isothiocyanate, has gained attention due to its tremendous anticancer potential. Thus, an array of sulforaphane analogs were synthesized and evaluated for their cytotoxic potentials on a wide range of malignant cell lines. Among these derivatives, compound 4a displayed exceptional potency in inhibiting the proliferation of cancer cell lines and a negligible effect on normal cell lines through G2/M phase arrest. The lead compound induced reactive oxygen species (ROS)-mediated mitochondrial dysfunction, leading to apoptosis. Further mechanistic studies established the interaction of the compound 4a with the insulin-like growth factor-1 receptor (IGF-R1) and blocking of the phosphatidylinositol-3-kinase (PI3K)-protein kinase B (PKB/Akt) pathway. This led to suppression of nuclear factor erythroid 2-related factor 2 (NRF-2) protein expression, thus increasing the free radicals in the tumor cells. Moreover, compound 4a induced ROS-mediated caspase-independent apoptosis. Finally, compound 4a reduced tumor progression in a 4T1 injected BALB/c syngeneic mice tumor model. In conclusion, this study summarizes the mechanism of compound 4a-mediated ROS-mediated caspase-independent apoptosis. According to the study's findings, compound 4a can be used as a powerful new anticancer agent to enhance cancer treatment.

Organocatalyzed preparation of 1,4,5-trisubstituted-glycosyl-1,2,3-triazole derivatives.

Organocatalytic coupling of glycosyl azides with enolates of active ketones and esters through azide-enolate [3 + 2] cycloaddition in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) furnished 1,4,5-trisubstituted-glycosyl-1,2,3-triazole derivatives in excellent yield. The reaction condition is simple and can be scaled-up. Graphical abstract Coupling of glycosyl azides with active ketones through azide-enolate [3 + 2] cycloaddition in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) furnished 1,4,5-trisubstituted-glycosyl-1,2,3-triazole derivatives in excellent yield.

Natural product inspired allicin analogs as novel anti-cancer agents.

A series of novel analogs of Allicin (S-allyl prop-2-ene-1-sulfinothioate) present in garlic has been synthesized in high yield. Synthesized 23 compounds were evaluated against different breast cancer cells (MDA-MB-468 and MCF-7) and non-cancer cells (WI38). Four compounds (3f, 3h, 3m and 3u) showed significant cytotoxicity against cancer cells whereas nontoxic to the normal cells. Based on the LD50 values and selectivity index (SI), compound 3h (S-p-methoxybenzyl (p-methoxyphenyl)methanesulfinothioate) was considered as most promising anticancer agent amongst the above three compounds. Further bio-chemical studies confirmed that compound 3h promotes ROS generation, changes in mitochondrial permeability transition and induced caspase mediated DNA damage and apoptosis.

Expedient synthesis of the pentasaccharide repeating unit of the O-antigen of Escherichia coli O86 and its conformational analysis.

Synthesis of the pentasaccharide with a 2-aminoethyl linker attached to the reducing end corresponding to the cell wall O-antigen of Escherichia coli O86 strain is reported. The synthetic strategy involves sequential glycosylation of suitably protected monosaccharide intermediates under similar glycosylation reaction conditions. Thioglycosides have been used as glycosyl donor throughout the synthetic strategy. Conformational analysis of the synthesized pentasaccharide has been carried out using 2D ROESY NMR spectral analysis and all atom explicit molecular dynamics (MD) simulation technique. Graphical abstract Facile synthesis of the pentasaccharide with a 2-aminoethyl linker attached to the reducing end corresponding to the cell wall O-antigen of Escherichia coli O86 strain is reported. Conformational analysis of the synthesized pentasaccharide has been carried out using 2D ROESY NMR spectral analysis and all atom explicit molecular dynamics (MD) simulation technique.

Efficient synthesis of the tetrasaccharide repeating unit of the O-antigen of Escherichia coli O174 strain.

The tetrasaccharide repeating unit of the O-antigen of Escherichia coli O174 strain was synthesized applying sequential glycosylations of suitably functionalized monosaccharide intermediates. Activation of glycosyl trichloroacetimidate derivatives using nitrosyl tetrafluoroborate (NOBF4) has been used during the synthesis. The glycosylation steps were high yielding with satisfactory stereo outcome.