Synthesis, topology, molecular docking and dynamics studies of -phenylenediamine derivative.

The N, N'-(1,2-phenylene) bis (1- (4- chlorophenyl) methanimine) (CS4) was synthesized and characterized by infrared (IR), absorption (UV-vis) and NMR (H and C) spectral analyses. The structural parameters, vibrational frequencies, potential energy and the distribution analysis (PED) were calculated by using DFT with the basis set of B3LYP/cc-pVDZ and these spectral values were compared to the experimental values. HOMO and LUMO studied were performed in order to understand the stability and biological activity of the compound.

Pyto-Architechture of Ag, Au and Ag-Au bi-metallic nanoparticles using waste orange peel extract for enable carcinogenic Congo red dye degradation.

Ecologically inspired to develop silver, gold and silver/gold bimetallic nanoparticles from discarded orange peel extract. The plant-derived compounds included in discarded orange peel extract have been accountable for the development of Ag, Au and Ag-Au bimetallic nanoparticles, that might be used in the biosynthetic process. The qualitative assessment of developed silver, gold and silver/gold bimetallic nanoparticles has been performed by UV-visible, XRD pattern, FT IR analysis, TEM/HRTEM, EDX and BET isotherm analysis.

Antimicrobial activity prediction, inter- and intramolecular charge transfer investigation, reactivity analysis and molecular docking studies of adenine derivatives.

The utilization of the density functional theory (DFT) methodology has developed as a highly efficient method for investigating molecular structure and vibrational spectra, and it is increasingly being employed in various applications relating to biological systems. This study focuses on conducting investigations, both experimental and computed, to analyze the molecular structure, electronic properties and features of (E)-4-(((9H-purin-6-yl)imino)methyl)-2-methoxyphenol (ANVA). The expression ANVA should be rewritten as follows: the compound is a derivative of adenine (primary amine), specifically a vanillin (aldehyde).

Design of a Near Infrared Fluorescent Ureter Imaging Agent for Prevention of Ureter Damage during Abdominal Surgeries.

The inadvertent severing of a ureter during surgery occurs in as many as 4.5% of colorectal surgeries. To help prevent this issue, several near-infrared (NIR) dyes have been developed to assist surgeons with identifying ureter location.

Localization of Fluorescent Targets in Deep Tissue With Expanded Beam Illumination for Studies of Cancer and the Brain.

Imaging fluorescence through millimeters or centimeters of tissue has important in vivo applications, such as guiding surgery and studying the brain. Often, the important information is the location of one of more optical reporters, rather than the specifics of the local geometry, motivating the need for a localization method that provides this information. We present an optimization approach based on a diffusion model for the fast localization of fluorescent inhomogeneities in deep tissue with expanded beam illumination that simplifies the experiment and the reconstruction.

Comparison of a Short Versus Long Stokes Shift Near-Infrared Dye During Intraoperative Molecular Imaging.

Purpose: Intraoperative molecular imaging (IMI) utilizes optical dyes that accumulate within tumors to assist with detection during a cancer operation. IMI can detect disease not visualized preoperatively, as well as positive margins. However, these dyes are limited by autofluorescence, signal reflection, and photon-scatter.

A New Class of β-Pyrrolidino-1,2,3-Triazole Derivatives as β-Adrenergic Receptor Inhibitors: Synthesis, Pharmacological, and Docking Studies.

New 1,4-disubstituted β-pyrrolidino-1,2,3-triazoles were synthesized using a reusable copper-iodide-doped neutral alumina catalyst. Synthesis of diversely substituted triazoles and recyclability of CuI catalyst explains the broad scope of this protocol. The synthesized compounds were screened for their antimicrobial and anticancer properties.

Use of a Single CAR T Cell and Several Bispecific Adapters Facilitates Eradication of Multiple Antigenically Different Solid Tumors.

Most solid tumors are comprised of multiple clones that express orthogonal antigens, suggesting that novel strategies must be developed in order to adapt chimeric antigen receptor (CAR) T-cell therapies to treat heterogeneous solid tumors. Here, we utilized a cocktail of low-molecular-weight bispecific adapters, each comprised of fluorescein linked to a different tumor-specific ligand, to bridge between an antifluorescein CAR on the engineered T cell and a unique antigen on the cancer cell. This formation of an immunologic synapse between the CAR T cell and cancer cell enabled use of a single antifluorescein CAR T cell to eradicate a diversity of antigenically different solid tumors implanted concurrently in NSG mice.

Evaluation of Novel Tumor-Targeted Near-Infrared Probe for Fluorescence-Guided Surgery of Cancer.

Because the most reliable therapy for cancer involves quantitative resection of all diseased tissue, considerable effort has been devoted to improving a surgeon's ability to locate and remove all malignant lesions. With the aid of improved optical imaging equipment, we and others have focused on developing tumor-targeted fluorescent dyes to selectively illuminate cancer nodules during surgery. We describe here the design, synthesis, optical properties, in vitro and in vivo tumor specificity/affinity, pharmacokinetics, preclinical toxicology, and some clinical application of a folate receptor (FR)-targeted NIR dye (OTL38) that concentrates specifically in cancer tissues and clears rapidly from healthy tissues.

Carbonic Anhydrase IX-Targeted Near-Infrared Dye for Fluorescence Imaging of Hypoxic Tumors.

Use of tumor-targeted fluorescence dyes to help surgeons identify otherwise undetected tumor nodules, decrease the incidence of cancer-positive margins, and facilitate localization of malignant lymph nodes has demonstrated considerable promise for improving cancer debulking surgery. Unfortunately, the repertoire of available tumor-targeted fluorescent dyes does not permit identification of all cancer types, raising the need to develop additional tumor-specific fluorescent dyes to ensure localization of all malignant lesions during cancer surgeries. By comparing the mRNA levels of the hypoxia-induced plasma membrane protein carbonic anhydrase IX (CA IX) in 13 major human cancers with the same mRNA levels in corresponding normal tissues, we document that CA IX constitutes a nearly universal marker for the design of tumor-targeted fluorescent dyes.

Targeting of a Photosensitizer to the Mitochondrion Enhances the Potency of Photodynamic Therapy.

Photodynamic therapy (PDT) involves use of a photosensitizer, whose activation with light leads to the production of singlet oxygen (SOS), generation of reactive oxygen species (ROS), and initiation of associated cell toxicity. Because a cell's mitochondria constitute sites where oxygen levels are high, ROS can be readily produced, and apoptosis is commonly initiated. Therefore, an ideal PDT agent might be a potent photosensitizer that could naturally accumulate in mitochondria.

Intraoperative Ureter Visualization Using a Novel Near-Infrared Fluorescent Dye.

Ureters can be accidentally severed during pelvic surgeries, significantly prolonging the times in the operating room to allow for complete repair of damaged ureters and leading to significant morbidities associated with consequent ureter obstruction and possible kidney dysfunction. In an effort to prevent these complications, light-emitting stents and urine-excreted dyes have been introduced to illuminate the ureter during surgery. However, problems with mechanical insertion, ureter spasm, image contrast, and localized injection have limited interest in their clinical applications.

Evaluation of a Centyrin-Based Near-Infrared Probe for Fluorescence-Guided Surgery of Epidermal Growth Factor Receptor Positive Tumors.

Tumor-targeted near-infrared fluorescent dyes have the potential to improve cancer surgery by enabling surgeons to locate and resect more malignant lesions where good visualization tools are required to ensure complete removal of malignant tissue. Although the tumor-targeted fluorescent dyes used in humans to date have been either small organic molecules or high molecular weight antibodies, low molecular weight protein scaffolds have attracted significant attention because they penetrate solid tumors almost as efficiently as small molecules, but can be infinitely mutated to bind almost any antigen. Here we describe the use of a 10 kDa protein scaffold, a Centyrin, to target a near-infrared fluorescent dye to tumors that overexpress the epidermal growth factor receptor (EGFR) for fluorescence-guided surgery (FGS).

Synthesis of function-oriented 2-phenyl-2H-chromene derivatives using L-pipecolinic acid and substituted guanidine organocatalysts.

Organocatalytic domino oxa-Michael/aldol reactions between salicylaldehyde with electron deficient olefins are presented. We screened guanidine, 1,1,3,3-tetramethylguanidine (TMG) and L-pipecolinic acid as organocatalysts for this transformation. 3-Substituted 2-phenyl-2H-chromene derivatives are synthesized with high yields and with poor enantioselectivity (5-17% ee) using L-pipecolinic acid while TMG works well with cinnamaldehyde without using co-catalyst.

Design and Synthesis of Potential New Apoptosis Agents: Hybrid Compounds Containing Perillyl Alcohol and New Constrained Retinoids.

Novel retinoids 1-3 containing perillyl alcohol were synthesized through the addition of perillyl alcohol to the activated carboxylic acids (retinoids) promoted by DCC (N, N'-Dicylohexyl cabodiimide). A set of structurally and functionally diverse perillyl alcohol derivatives of retinoids were obtained in good yields (78-82%). Biological evaluation of these novel hybrid compounds (containing retinoids and perillyl alcohol) is currently underway in our laboratory.

Design and synthesis of novel pinacolylboronate containing combretastatin 'antimitotic agent' analogues.

We developed a procedure to synthesize pinacolyl boronate containing stilbene derivatives and used this procedure to synthesize boron-containing combretastatin analogues. The key step involves the Wittig reaction of the ylide 4-(4,4,5,5-tetramethyl-1,3,2-dioxaboratophenyl)-methyl triphenylphosphonium bromide 11 with 3,4,5-trimethoxy benzaldehyde in the presence of (t)BuONa in DMF, providing 88% yield. We are now in a position to evaluate the biological activity of these derivatives as modulators of TGF-beta signaling pathways.

Design and synthesis of (E)-1-((3-ethyl-2,4,4-trimethylcyclohex-2-enylidene)methyl-4-substituted benzenes from 1-(2,6,6-trimethylcyclohex-1-enyl)ethanol.

A novel strategy for synthesizing (E)-1-((3-ethyl-2,4,4-trimethylcyclohex-2-enylidene)methyl-4-substituted benzenes from 1-(2,6,6-trimethylcyclohex-1-enyl)ethanol has been developed; the allylic alcohol was treated with PPh(3).HBr in methanol followed by aldehydes in the presence of a base and furnished the 1,3-dienes in moderate to good yields (79-86%).

Propargyl bromide as an excellent alpha-bromoacetone equivalent: convenient and new route to alpha-aroylacetones.

[reaction: see text] A variety of alpha-aroylacetones 4a-g have been prepared in excellent yields following a new protocol wherein alpha-aminonitriles 1a-g as the aryl acyl anion equivalents readily react with propargyl bromide as the alpha-bromoacetone equivalent. The alkylated product undergoes one-pot unmasking of the keto functionality along with Markovnikov's hydration of the terminal alkyne with CuSO4 x 5H2O in aqueous methanol at 60 degrees C to furnish the desired target in excellent isolated yields.