Development of an integrated metabolomic profiling approach for infectious diseases research

Metabolomic profiling offers direct insights into the chemical environment and metabolic pathway activities at sites of human disease. During infection, this environment may receive important contributions from both host and pathogen. Here we apply an untargeted metabolomics approach to identify compounds associated with an E. coli urinary tract infection population. Correlative and structural data from minimally processed samples were obtained using an optimized LC-MS platform capable of resolving ~2300 molecular features. Principal component analysis readily distinguished patient groups and multiple supervised chemometric analyses resolved robust metabolomic shifts between groups. These analyses revealed nine compounds whose provisional structures suggest candidate infection-associated endocrine, catabolic, and lipid pathways. Several of these metabolite signatures may derive from microbial processing of host metabolites. Overall, this study highlights the ability of metabolomic approaches to directly identify compounds encountered by, and produced from, bacterial pathogens within human hosts.     

Synthesis of Benzofuran Derivatives: One Pot Synthesis of 2(3H) Benzofuranones

Phenols are condensed with cinnamic acids in the presence of trifluoroacetic acid to give high yields of the corresponding 2(3H) benzofuranones.     

Ferulic Acid: A Natural Phenol That Inhibits Neoplastic Events through Modulation of Oncogenic Signaling

Despite the immense therapeutic advances in the field of health sciences, cancer is still to be found among the global leading causes of morbidity and mortality. Ethnomedicinally, natural bioactive compounds isolated from various plant sources have been used for the treatment of several cancer types and have gained notable attention. Ferulic acid, a natural compound derived from various seeds, nuts, leaves, and fruits, exhibits a variety of pharmacological effects in cancer, including its proapoptotic, cell-cycle-arresting, anti-metastatic, and anti-inflammatory activities. This review study presents a thorough overview of the molecular targets and cellular signaling pathways modulated by ferulic acid in diverse malignancies, showing high potential for this phenolic acid to be developed as a candidate agent for novel anticancer therapeutics. In addition, current investigations to develop promising synergistic formulations are also discussed.     

Canine Parvovirus Type 2a (CPV-2a)-Induced Apoptosis in MDCK Involves Both Extrinsic and Intrinsic Pathways

The canine parvovirus type 2 (CPV-2) causes an acute disease in dogs. It has been found to induce cell cycle arrest and DNA damage leading to cellular lysis. In this paper, we evaluated the apoptotic potential of the “new CPV-2a” in MDCK cells and elucidated the mechanism of the induction of apoptosis. The exposure of MDCK cells to the virus was found to trigger apoptotic response. Apoptosis was confirmed by phosphatidylserine translocation, DNA fragmentation assays, and cell cycle analysis. Activation of caspases-3, -8, -9, and -12 and decrease in mitochondrial potential in CPV-2a-infected MDCK cells suggested that the CPV-2a-induced apoptosis is caspase dependent involving extrinsic, intrinsic, and endoplasmic reticulum pathways. Increase in p53 and Bax/Bcl2 ratio was also observed in CPV-2a-infected cells.     

O-Alkyl Trithiophosphate Derivatives of Triorganotin(IV) and S-Alkyl Trithiophosphate Derivatives of Diorganotin(IV) Chloride

Reactions of triorganotin chlorides with potassium salt of O-alkyl trithiophosphate [ROP(S)(SK)₂; R = Me, Prⁱ, Ph] in 2:1 molar ratio in anhydrous benzene yield triorganotin O-alkyl trithiophosphate of the type ROP(S) [SSnR′₃]₂ R = Me, Prⁱ; Ph, R′ = Prⁿ, Buⁿ, Ph] which are found to be monomeric in nature. These complexes are soluble in common organic solvents. Similar reactions of diorganotin chloride with dipotassium salt of S-alkyl trithiophosphate yield diorganotin-S-alkyl trithiophosphate of the type [(RS)P(O)S₂]₂SnR′₂; R = Me, Prⁱ; R′ = Me, Et, Ph, which also are found to be monomeric in nature and are soluble in common organic solvents. The newly synthesized derivatives have been characterized by physicochemical and spectroscopic techniques, IR, NMR (¹H, ³¹P, and ¹¹⁹Sn).     

From Linear to Angular Isomers: Achieving Tunable Charge Transport in Single‐Crystal Indolocarbazoles Through Delicate Synergetic CH/NH⋅⋅⋅π Interactions

Weak intermolecular interaction in organic semiconducting molecular crystals plays an important role in molecular packing and electronic properties. Here, four five‐ring‐fused isomers were rationally designed and synthesized to investigate the isomeric influence of linear and angular shapes in affecting their molecular packing and resultant electronic properties. Single‐crystal field‐effect transistors showed mobility order of 5,7‐ICZ (3.61 cm² V^?1 s^?1) >5,11‐ICZ (0.55 cm² V^?1 s^?1) >11,12‐ICZ (ca. 10^?5 cm² V^?1 s^?1) and 5,12‐ICZ (ca. 10^?6 cm² V^?1 s^?1). Theoretical calculations based on density functional theory (DFT) and polaron transport model revealed that 5,7‐ICZ can reach higher mobilities than the others thanks to relatively higher hole transfer integral that links to stronger intermolecular interaction due to the presence of multiple NH???π and CH???π(py) interactions with energy close to common NH???N hydrogen bonds, as well as overall lower hole‐vibrational coupling owing to the absence of coupling of holes to low frequency modes due to better π conjugation.     

An X-band time domain electron paramagnetic resonance spectrometer

A computer-controlled X-band time domain electron paramagnetic resonance (EPR) spectrometer, with a time resolution of the order of 0.5μsec, has been constructed with many of the crucial microwave components designed and fabricated by the Microwave Engineering Group of TIFR. The spectrometer operates either in a microwave power pulsed mode for determination of spin-lattice relaxation times by the saturation recovery technique or in the kinetic mode for determination of the time dependence of EPR signal after laser excitation. It has an automatic frequency control, an automatic phase control and, most importantly, a field-frequency lock which ensures good stability of the EPR line positions enabling signal averaging for extended periods. The constructional details of the spectrometer and its performance in both the modes are described here by reporting results on certain typical systems.