Synthesis and biological evaluation of novel photo-clickable adenosine and cyclic ADP-ribose analogs: 8-N-2'-O-propargyladenosine and 8-N-2'-O-propargyl-cADPR.

A photo-clickable analog of adenosine was devised and synthesized in which the photoactive functional group (8-azidoadenosine) and the click moiety (2'-O-propargyl-ether) were compactly combined within the structure of the adenosine nucleoside itself. We synthesized 8-N-2'-O-propargyl adenosine in four steps starting from adenosine. This photo-clickable adenosine was 5'-phosphorylated and coupled to nicotinamide mononucleotide to form the NAD analog 8-N-2'-O-propargyl-NAD.

Synthesis and Evaluation of PPARδ Agonists That Promote Osteogenesis in a Human Mesenchymal Stem Cell Culture and in a Mouse Model of Human Osteoporosis.

We synthesized a directed library of compounds to explore the structure-activity relationships of peroxisome proliferator-activated receptor δ (PPARδ) activation relative to mesenchymal stem cell (MSC) osteogenesis. Our scaffold used para-substituted cinnamic acids as a polar headgroup, a heteroatom and heterocycle core connecting units, and substituted phenyl groups for the lipophilic tail. Compounds were screened for their ability to increase osteogenesis in MSCs, and the most promising were examined for subunit specificity using a quantitative PPAR transactivation assay.

Highly sensitive UHPLC-MS/MS method for the simultaneous estimation of propafenone and its metabolites 5-hydroxypropafenone and N-depropylpropafenone on human dried blood spots technique and application to a pharmacokinetic study.

A highly sensitive, rapid and selective UHPLC-MS/MS method has been developed and validated for quantification of the propafenone (PF), 5-hydroxypropafenone (5-OHPF) and N-depropylpropafenone (N-DPF) on human dried blood spot (DBS). The assay procedure involves a solid-liquid extraction of PF, 5-OHPF and N-DPF and amlodipine (internal standard, I.S.