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New Biological Targets for the Treatment of Leishmaniasis
Published in Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay, Medicinal Chemistry of Neglected and Tropical Diseases, 2019
Fabrizio Carta, Andrea Angeli, Christian D.-T. Nielsen, Claudiu T. Supuran, Agostino Cilibrizzi
Both methodologies rely upon the activation of the carboxylic acid moiety to a redox active ester which could be isolated or reacted in situ. Even though the mechanism proceeds via a radical pathway (confirmed by Aggarwal’s studies employing radical clock experiments), the methodology could functionalize a variety of complex natural products, demonstrating exquisite control not often associated with traditional radical chemistry (Figures 18A and B). Of note, a borono-vancomycin analogue was obtained as a single diastereomer from vancomycin (Li et al. 2017). Aggarwal (A) and Baran’s (B) decarboxylative borylations. THF = tetrahydrofuran; DMF = dimethylformamide; B2Pin2 = bis(pinacolato)diboron; DMAc = N,N-dimethylacetamide.
Nonisotopic Labeling
Published in Lelio G. Colombetti, Principles of Radiopharmacology, 2019
Certain chemical entities may be labeled with a conjugating reagent that has been previously iodinated. Such a reagent is N-succinimidyl-3(4-hydroxy-5[I-125]iodophenyl) propionate known as the Bolton-Hunter reagent. This reagent is based on an active ester used as a mild conjugating reagent in peptide chemistry that reacts with free amino groups such as the epsilon amino side chains of lysine residues or N-terminal amino acids (Figure 3).
Radiopharmaceuticals for SPECT
Published in Martin G. Pomper, Juri G. Gelovani, Benjamin Tsui, Kathleen Gabrielson, Richard Wahl, S. Sam Gambhir, Jeff Bulte, Raymond Gibson, William C. Eckelman, Molecular Imaging in Oncology, 2008
Chemotherapeutics and their analogs radiolabeled with PET and SPECT radionuclides have been prepared to directly measure the drug efflux status of tumors prior to and during chemotherapy. Radioiodinated analogs include daunorubicin (94), doxorubicin (94), and paclitaxel (95,96). Daunorubicin, doxorubicin, and their radioiodinated analogs are shown in Figure 4. Compounds 1 and 2 were prepared by reacting the chemotherapeutic with the appropriate stannane containing active ester followed by radioiodination-destannylation. Compounds 3 and 4 were prepared by direct radioiodination of an N-benzylphenol derivative. Paclitaxel, its stannane radioiodination precursor 5 and radioiodinated analog 6 are shown in Figure 5. Radiolabeling at this position was performed because it has been demonstrated that paclitaxel analogs with a halogen on this position were as biologically active as paclitaxel (97).
Bisphosphonate-functionalized micelles for targeted delivery of curcumin to metastatic bone cancer
Published in Pharmaceutical Development and Technology, 2020
Sumedh Kamble, Pegah Varamini, Markus Müllner, Théophile Pelras, Ramin Rohanizadeh
In this study, alendronate (i.e. an anti-bone resorptive and bone binding drug) was covalently conjugated to Pluronic F127 using carbodiimide chemistry, a standard approach for –COOH to –NH2 conjugation. However, the use of water-soluble carbodiimide (EDC.HCl) linker was critical in this study due to the very low or no solubility of alendronate in an organic solvent. EDC.HCl forms active ester to couple with amines and has already been extensively used to conjugate biomolecules and antibodies (East et al. 2011). The modification of Pluronic F127 and consequent conjugation steps were confirmed by 1H-NMR, 31P-NMR and FT-IR spectroscopy. Complete modification of the Pluronic F127 termini was qualitatively and quantitatively observed by FT-IR and 1H-NMR respectively. The subsequent conjugation of alendronate was monitored by 1H-NMR and 31P-NMR, with no evidence of the presence of remaining precursors (Figure 1).
Efficacy of Concanavalin-A conjugated nanotransfersomal gel of apigenin for enhanced targeted delivery of UV induced skin malignant melanoma
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Manmohan S. Jangdey, Chanchal Deep Kaur, Swarnlata Saraf
The successful synthesis of the conjugates was confirmed by IR and DSC study. The conjugation of Con-A to the nanotransfersomes was done through the crosslinking of EDC-NHS on the surface of transfersome. Con-A coupling to the nanotransfersomes was done by the carbodiimide technique. 1-Ethyl-3, 3-(dimethylaminopropyl) carbodiimide (EDC) is a water-soluble derivative of carbodiimide. N-Hydroxysuccinimide (NHS) is often used to assist the carbodiimide coupling in the presence of EDC. The reaction includes the formation of the intermediate active ester (the product of condensation of the carboxylic group and NHS) that further reacts with the amine function to yield finally the amide bond. IR studies confirmed the attachment of Con-A with nanotransfersomes, because the coupling of Con-A and transfersomes was dependent on the amide bond between NH2 group of Con-A and OH group of apigenin.
Recent advances in lipopolysaccharide-based glycoconjugate vaccines
Published in Expert Review of Vaccines, 2021
Henderson Zhu, Christine S. Rollier, Andrew J. Pollard
Active ester chemistry was incorporated in two LPS-based vaccine candidates. More recently, a vaccine candidate comprising synthetic pentasaccharide of B. pertussis O-SP to bacteriophage Qβ showed a three-fold higher anti-carbohydrate IgG response compared with control groups receiving Qβ alone [74]. The method can also be adapted to conjugating O-Ag isolated from bacteria by additional linkers such as ADH, as seen in a S. Paratyphi A vaccine candidate demonstrated higher anti-O-Ag IgG titers in mice than administering O-Ag alone [120].