Ranjana S. Khanna

Copper-free palladium-catalyzed Sonogashira coupling-annulation: efficient one-pot synthesis of functionalized pyrano[4,3-b]quinolines from 2-chloro-3-formylquinolines.

A convenient, one-pot, copper-free, Pd-catalyzed methodology has been described for the synthesis of 1,3-disubstituted pyrano[4,3-b]quinolines from 2-chloro-3-formylquinolines. Formation of annulated products 3 is attributed to the presence of Pd(OAc)2 and PPh3. Further, PPh3 in the reaction mixture promotes the cyclization by reducing the reaction time and increasing the yield of cyclized product.

Evaluation of biomarkers of oxidative stress and antioxidant capacity in the cord blood of preterm low birth weight neonates

Objective: The objective of the study is to investigate the association between oxidative stress markers and enzymatic / non-enzymatic antioxidants (marker of the resistance in body to oxidative damage) in the cord blood of preterm low birth weight (LBW) neonates. Methods: Malondialdehyde (MDA), carbonyl proteins, total antioxidant capacity and Vitamin A, E and C levels in the cord blood were determined by spectrophotometry. Results: Increased lipid peroxidation, protein oxidation with decreased values of vitamin A, E, C and total antioxidant capacity were observed in the preterm LBW newborns. Observations of negative correlation between MDA and protein carbonyl with antioxidants vitamin A, E and C and total antioxidant status points towards the existence of oxidative stress in the preterm LBW newborns. Conclusions: Poor fetal growth affects the development of antioxidant defenses of preterm LBW babies, predisposing them to higher oxidative stress, which in turn may partly account for increased morbidity and mortality in these infants. The presence of an association between oxidative stress biomarkers and enzymatic /non-enzymatic antioxidants in the cord blood of preterm LBW neonates suggest that increased oxidative stress may be the result of changes in the levels of certain enzymatic and non-enzymatic antioxidants due to the cause or the effect of oxidative damage occurring at the molecular level.

Regioselective synthesis of fused imidazo[1,2-a]pyrimidines via intramolecular C-N bond formation/6-endo-dig cycloisomerization.

An efficient regioselective cascade synthesis of N-fused imidazo heterocycles has been developed. This cascade transformation proceeds via a transition-metal (copper/silver) catalyzed coupling reaction between 2-aminobenzimidazole, aldehydes, and alkynes leading to the formation of propargylamine intermediate, which regioselectively undergoes 6-endo-dig cyclization through intramolecular N-H bond activation interceded C-N bond formation leading to highly functionalized imidazo[1,2-a]pyrimidines in good to excellent yields.

Association of oxidative DNA damage, protein oxidation and antioxidant function with oxidative stress induced cellular injury in pre-eclamptic/eclamptic mothers during fetal circulation.

Pre-eclampsia is a devastating multi system syndrome and a major cause of maternal, fetal, neonatal morbidity and mortality. Pre-eclampsia is associated with oxidative stress in the maternal circulation. To have an insight on the effect of pre-eclampsia/eclampsia on the neonates, the study was made to explore the oxidative status by quantification of byproducts generated during protein oxidation and oxidative DNA damage and deficient antioxidant activity in umbilical cord blood of pre-eclamptic/eclamptic mothers during fetal circulation. Umbilical cord blood during delivery from neonates born to 19 pre-eclamptic mothers, 14 eclamptic mothers and 18 normotensive mothers (uncomplicated pregnancy) as control cases was collected. 8-OHdG (8-hydroxy-2-deoxyguanosine), protein carbonyl, nitrite, catalase, non-enzymatic antioxidants (vitamin A, E, C), total antioxidant status and iron status were determined. Significant elevation in the levels of 8-OHdG, protein carbonyl, nitrite and iron along with decreased levels of catalase, vitamin A, E, C, total antioxidant status were observed in the umbilical cord blood of pre-eclamptic and eclamptic pregnancies. These parameters might be influential variables for the risk of free radical damage in infants born to pre-eclamptic/eclamptic pregnancies. Increased oxidative stress causes oxidation of DNA and protein which alters antioxidant function. Excess iron level and decreased unsaturated iron binding capacity may be the important factor associated with oxidative stress and contribute in the pathogenesis of pre-eclampsia/eclampsia which is reflected in fetal circulation.

Oxidative damage markers as possible discriminatory biomarkers in breast carcinoma

The study was designed to evaluate the markers of oxidative damage and to establish their diagnostic utility in breast carcinoma patients. Levels of 8-hydroxy-2-deoxyguanosine (8-OH-dG), protein carbonyl (PC), and malondialdehyde (MDA) along with total antioxidant status (TAS) were measured in breast carcinoma patients and controls. Receiver operating characteristic (ROC) analysis was done to study the diagnostic potential of the oxidative damage markers. Significant increases in oxidative damage markers were observed in breast carcinoma patients compared with the normal controls, which were accompanied by significant decrease in TAS. The logistic regression analysis revealed higher levels of oxidative stress marker and reduced level of TAS were significantly associated with breast cancer. ROC curves analysis demonstrates that 8-OHdG and PC are better indicators for distinguishing cancer patients from controls, followed by MDA and TAS. Our results indicate increased oxidative damage is associated with malignancy in breast cancer patients. High accuracy of oxidative stress markers in indicating cancer presence can be used as discriminatory makers for efficient diagnosis.

Vascular Endothelial Growth Factor Levels in Relation to Oxidative Damage and Antioxidant Status in Patients with Breast Cancer

Purpose Oxidative stress and angiogenesis are important elements in the pathogenesis of inflammatory diseases and cancer. Vascular endothelial growth factor (VEGF) is one of the most potent angiogenic cytokines and is up-regulated by conditions associated with the generation of free radicals and reactive oxygen intermediates. In this study, we investigated the association between oxidative stress and serum VEGF status in patients with breast cancer. Methods Forty patients with breast carcinoma, of which 21 were stage II and 19 were stage III, along with 40 age- and gender-matched healthy controls were enrolled. Oxidative stress, total antioxidant status, and VEGF levels in serum were evaluated by spectrophotometric procedures. Malondialdehyde (MDA) levels were measured and antioxidant status was assessed by measuring total antioxidant status (TAS) to assess oxidative damage. Results VEGF and MDA levels were significantly higher in patients with breast cancer than those of controls (p<0.005). Total antioxidant level decreased significantly in patients compared to that in controls. MDA, TAS, and VEGF levels were also analyzed based on menopausal status and different clinical disease stages. MDA and TAS level significantly different in the postmenopausal group than the premenopausal group, whereas VEGF level remained unchanged. Conclusion Increased VEGF level and its positive correlation with oxidative stress level and decreased antioxidant status suggest a link between oxidative stress and malignant transformation.

Cascade synthesis of 2-pyridones using acrylamides and ketones

Microwave assisted non-catalytic condensation of 2-cyanoacetamide with aromatic aldehydes, and enolate mediated Michael-type addition to acrylamide followed by oxidative cyclization, produce 2-pyridones in good to excellent yield. Unsymmetrical ketones produce two regioisomeric enolates, therefore thermodynamic and kinetic products of butan-2-one and pentan-2-one have been isolated and fully characterized.

Novel diastereoselective synthesis of spiropyrrolidine-oxindole derivatives as anti-breast cancer agents

A novel class of diastereoselective spiropyrrolidine-oxindole derivatives were synthesized from isatin, 2-phenylthiazolidine-4-carboxylic acid and chalcone in a one-pot multicomponent reaction via 1,3-dipolar cycloaddition. The advantages of this methodology are the mild reaction conditions, high diastereoselectivity and high yield. These derivatives exhibited promising anti-cancer activity against the human breast cancer cell lines.

Role of arene interactions and substituent effects in conformational (syn/anti) control of 1,2-diarylethanes

Conformational analysis of nine designed flexible 1,2-diarylethanes with different substituents show syn conformation due to π–π interactions by 1H NMR in solution, this carries over to the solid state for three compounds while two show anti conformation in the solid state by X-ray crystallography and the remaining compounds do not give diffraction quality crystals.

Selective induced polarization through electron transfer in acetone and pyrazole ester derivatives via C–H⋯OC interaction

A set of organic compounds (pyrazole ester derivatives, viz. 5-[3-(substituted)-propoxy]-3-methyl-1-phenyl-1H-pyrazole-4-carboxylic acid methyl ester and 5-[2-(substituted)-ethoxy]-3-methyl-1-phenyl-1H-pyrazole-4-carboxylic acid methyl ester) was synthesized and their affinity and stability towards the acetone molecule were tested by NMR. Further, the host–guest complex formed has been studied by cyclic voltammetric titration. Interestingly, the acetone molecule selectively bound to the methyl group of the pyrazole moiety and stabilized the system. These findings are also supported by quantum chemical calculations using the DFT/B-LYP/TZVPP method. Apart from hydrogen bonding, an important role in stabilizing the complex is also played by the C–H⋯π interaction governed by dispersion energy. The study proves that a methyl-substituted pyrazol ester can act as a receptor for acetone.