African trypanosomiasis is a parasitic disease of humans and animals that plagues sub-Saharan Africa and is transmitted by tsetse flies. The infection is known as sleeping sickness in humans and is lethal if left untreated. However, the choice of chemotherapeutic agents is very limited, and approved drugs have many side effects. Diminazene (berenil) is used in the treatment of domestic animals ...

Synthesis on solid phase is one of modern methodologies especially useful in parallel and combinatorial syntheses. Tertiary amine functionalities are found in many important classes of catalysts, reagents and biologically active compounds. The tertiary N-methyl group is also present in structures of tropane alkaloids and majority of synthetic tropane derivatives with potential biological activi...

Previous investigations using an He-Ne laser-induced thrombosis method have shown that stroke-prone spontaneously hypertensive rats (SHRSP) have an enhanced thrombotic tendency in vivo compared to normotensive, Wistar Kyoto rats (WKY). In addition, studies in the presence of acetylcholine have suggested the presence of endothelial dysfunction in SHRSP. In contrast, shear-induced platelet reacti...

Nuclear receptors (NRs) complexed with agonist ligands activate transcription by recruiting coactivator protein complexes. In principle, one should be able to inhibit the transcriptional activity of the NRs by blocking this transcriptionally critical receptor-coactivator interaction directly, using an appropriately designed coactivator binding inhibitor (CBI). To guide our design of various cla...

We have previously reported the synthesis of SMA41, a unimolecular combination of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) of the quinazoline class and a DNA-damaging monomethyltriazene termed "combimolecule". Hydrolysis of 1-[4-(m-tolylamino)-6-quinazolinyl]-3-methyltriazene (SMA41) gives rise to an intact TKI [6-amino-4-(3-methylanilino)quinazoline; SMA52] ca...

Resistance of mouse M5076 (M5) ovarian reticular cell sarcoma to cyclophosphamide (CTX) was obtained in vivo by repeated drug treatment followed by transplantation of the regrowing tumor. After 16 passages, we obtained an M5 subline resistant to CTX (M5-CTX-16R). Median survival times were approximately 29 and 39 days for M5 and M5-CTX-16R, respectively. Survival of M5-bearing mice given a sing...