ABSTRACT
A series of four oxime-linked octavalent sialic acid and oligosialic acid poly(ether amidoamine) glycodendrimers were synthesized. In the attachment of the sialic acids to the dendrimer core, chemoselective oxime bonds were formed between the unprotected sugars (sialic acid or α-2,8-linked di- through tetra-sialic acids) and the aminooxy-terminated dendrimer core in a microwave-mediated reaction, resulting in good to excellent yields (58-100%) of the fully functionalized octavalent glycodendrimers. Next, using a combination of 1D and 2D nuclear magnetic resonance and working from the inside outward, we employed a systematic method to assign the proton and carbon signals starting with the smallest linkers and dendrimer cores and moving gradually up to the completed octavalent glycodendrimers. Through this approach, the assignment of the protons and carbons was possible, including the E- and Z-isomers related to the oxime dendrimer to sugar connections and relative quantities of each. These glycodendrimers were designed as broad-spectrum inhibitors of viral pathogens.
Subject(s)
Dendrimers , N-Acetylneuraminic Acid , N-Acetylneuraminic Acid/chemistry , Oximes/chemistry , Dendrimers/chemistry , Magnetic Resonance Spectroscopy , Sialic AcidsSubject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , COVID-19/diagnosis , Fever/diagnosis , Melanoma/drug therapy , Skin Neoplasms/drug therapy , Aged, 80 and over , COVID-19/complications , COVID-19/immunology , COVID-19/virology , COVID-19 Nucleic Acid Testing , Diagnosis, Differential , Female , Fever/chemically induced , Fever/immunology , Fever/virology , Humans , Imidazoles/adverse effects , Lung/diagnostic imaging , Melanoma/complications , Melanoma/secondary , Oximes/adverse effects , Pyridones/adverse effects , Pyrimidinones/adverse effects , RNA, Viral/isolation & purification , SARS-CoV-2/genetics , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Skin Neoplasms/complications , Tomography, X-Ray ComputedABSTRACT
Anaplastic thyroid carcinoma is the rarest tumor of the thyroid gland, representing less than 2% of clinically recognized thyroid cancers. Typically, it has an extremely rapid onset, fatal outcomes in most cases, and a median overall survival of 3 to 10 months despite aggressive multidisciplinary management. The presence of targetable mutations in anaplastic thyroid carcinoma patients is an opportunity for treatment when conventional therapeutics approaches are not effective, a frequent situation in the majority of patients. We present our experience in the management of a patient with unresectable anaplastic thyroid cancer who had a remarkable and rapid response to treatment with dabrafenib and trametinib during the COVID-19 pandemic. After four weeks of dabrafenib 150 mg twice daily plus trametinib 2 mg daily, he showed a dramatic reduction of the cervical mass around 90%. Nearly eight weeks under treatment with dabrafenib plus trametinib, the patient remains with minimal locoregional disease without distant metastases.