Published in Bioorganic & medicinal chemistry
Photoimmunotherapy (PIT) is a new molecular-targeted phototherapy in which administration of an antibody conjugated to IR700 (Ab-IR700, a phthalocyanine derivative) is followed by irradiation with near-infrared light. PIT induces cell death due to cell membrane damage, and the formation of IR700 aggregates on the cell membrane triggered by photoche...
Published in Bioorganic & medicinal chemistry
Core fucosylation is the attachment of an α-1,6-fucose moiety to the innermost N-acetyl glucosamine (GlcNAc) in N-glycans in mammalian systems. It plays a pivotal role in modulating the structural and biological functions of glycoproteins including therapeutic antibodies. Yet, few α-l-fucosidases appear to be capable of removing core fucose from in...
Published in Bioorganic & medicinal chemistry
Inhibition of PCAF bromodomain has been validated as a promising strategy for the treatment of cancer. In this study, we report the bioisosteric modification of the first reported potent PCAF bromodomain inhibitor, L-45 to its triazoloquinazoline bioisosteres. Accordingly, three new series of triazoloquinazoline derivatives were designed, synthesiz...
Published in Bioorganic & medicinal chemistry
Curcumin is a bioactive natural compound with a wide range of pharmacological properties, including antitumor activity; however, its clinical application has been limited because of its low solubility, stability, and bioavailability. In this study, a solid phase approach was proposed for the combinatorial synthesis of a mini library of the mimics o...
Published in Bioorganic & medicinal chemistry
Cytochrome P450 monooxygenases (P450s) are the major contributor in the metabolism of xenobiotics, including therapeutic agents. Thus, P450s find broad application in the pharmaceutical industry to synthesize metabolites of new active pharmaceutical ingredients in order to evaluate toxicity and pharmacokinetics. As an alternative to human hepatic P...
Published in Bioorganic & medicinal chemistry
We discovered 6-substituted thieno[2,3- d ]pyrimidine compounds ( 3 – 9 ) with 3–4 bridge carbons and side-chain thiophene or furan rings for dual targeting one-carbon (C1) metabolism in folate receptor- (FR) expressing cancers. Synthesis involved nine steps starting from the bromo-aryl carboxylate. From patterns of growth inhibition toward Chinese...
Published in Bioorganic & medicinal chemistry
TGR5 is emerging as an important and promising target for the treatment of diabetes, obesity and other metabolic syndromes. A series of novel 1-benzyl-1H-imidazole-5-carboxamide derivatives was designed, synthesized and evaluated in vitro and in vivo. The most potent compounds 19d and 19e exhibited excellent agonistic activities against hTGR5, whic...
Published in Bioorganic & medicinal chemistry
Amongst heterocyclic compounds, quinoline is an advantaged scaffold that appears as a significant assembly motif for the development of new drug entities. Quinoline and its derivatives tested with diverse biological activity constitute an important class of compounds for new drug development. Therefore, many scientific communities have developed th...
Published in Bioorganic & medicinal chemistry
B13 is an acid ceramidase (ACDase) inhibitor. The two chiral centers of this aromatic amido alcohol lead to four stereoisomers, yet we have little knowledge about its erythro- enantiomers, (1R, 2S) and (1S, 2R). In this paper, for the first time, the synthesis of two erythro- enantiomers is described, and the compounds are evaluated along with two ...
Published in Bioorganic & medicinal chemistry
A novel series of arylcarbamate-N-acylhydrazones derivatives have been designed and synthesized as potential anti-cholinesterase agents. In vitro studies revealed that these compounds demonstrated selective for butyrylcholinesterase (BuChE) with potent inhibitory activity. The compounds 10a-d, 12b and 12d were the most potent BuChE inhibitors with ...
