Two new pincer type N-heterocyclic carbene ligands were synthesized. The compounds were characterized by FTIR, NMR (1H, 13C) GC-MS and elemental analyses. They were also both modelled by DFT calculations as the crystal structure of 1,3-bis(acetamide)imidazol-3-ium bromide was determined by XRD w...

A study towards the kinetics of carbon dioxide (CO2) absorption into a novel aqueous solution of bis(3-aminopropyle)amine (APA) was carried out at 303, 308, 313 and 323 K over a concentration range of 0.1–0.5 kmol m−3 and different CO2 partial pressure. The reaction mechanism of CO2 with primar...

There is an urgent need for new anti-malarial drugs to combat the resurgence of resistance to current therapies. To exploit the A/T richness of malaria DNA as a potential target for anti-malarial drugs we tested an A/T-specific DNA synthesis inhibitor, adozelesin, for activity against Plasmodium...

Publisher SummaryThis chapter discusses heterosteroids and drug research. Heterosteroids may have heteroatoms as part of the steroid nucleus, or the heteroatoms may be extranuclear, forming part of a fused or spiro ring system, an attached group, or a side-chain. A relatively recent approach to ...

Rhodococcus sp. AJ270 is a useful biocatalyst for the synthesis of some enantiopure S-(+)-2-aryl-3-methylbutyric acids and R-(+)-2-aryl-3-methylbutyramides from the hydrolysis of 2-aryl-3-methylbutyronitriles under mild conditions. The nitrile-hydrolyzing enzymes involved in this novel microorga...

SM-5887 is an anthracycline antibiotic with a potent antitumor activity and low toxicity. The structure of the 2:1 SM-5887 -d(CGTACG) complex has been studied in solution by 2D NMR spectroscopy. These data revealed that SM-5887 intercalated between the cytosine and guanine residues and the sugar...

A photoactivatable diarylsulfonylurea, N-(4-azidophenylsulfonyl)-N′-(4-chlorophenyl)urea (LY219703), has been examined as a potential probe to elucidate the intracellular distribution and binding of antitumor diarylsulfonylureas. Our results demonstrated that against the human colon adenocarcin...

Treatment of NRK-52E (normal) and H/1.2-NRK-52E (Harvey-ras transfected NRK-52E) rat kidney epithelial-like cells with two Eli Lilly antitumor compounds, sulofenur and LY295501 (15.6μM–1000μM) resulted in concentration- and time-dependent cell killing. Cytosolic Ca2+ became elevated in both c...

Sulofenur was evaluated for fertility effects on rats. Five-week old male rats (20/group) received 0, 5, 30, or 60 mg Sulofenur/kg/day for 14 weeks. Fertility was evaluated five times. Treated males were mated with untreated females at 10 weeks. Half the males from each group were necropsied aft...

The effect of the antineoplastic drug sulofenur on the induction of the immediate-early genes (IEG) c-fos and c-jun and the stress gene hsp70 was compared in the rat kidney epithelial-like cell line NRK-52E and a derivative H-ras-transfected (H/1.2NRK-52E) cell line. Fold induction for each gene...

Sulofenur treatment (12.5 μM-1 mM) of colon adenocarcinoma cell lines resulted in dose- and time-dependent cell killing. LYc5 cells were viable longer than GC3c1, cells. Each concentration resulted in elevation of cytosolic calcium [Ca2+]i) for both cell lines. At lower doses, elevation was del...

The absorption and pharmacokinetics of sulofenur [N-(in- dan-5-sulfonyl)-N-(4-chlorophenyl)urea, LY186641] and its major metabolites were examined in mice, rats, monkeys, and dogs. The compound is a diarylsulfonylurea currently being evaluated as an oncolytic agent in phase I and II trials. In a...

D3 receptors are prominently localized in the primate caudate–putamen, and D3 receptor agonist properties may offer an advantage in Parkinson’s disease therapy. In the present experiments, we investigated the relationship between D3 receptor mRNA, D3 receptor sites and the dopamine transporter...

Parkinson's disease (PD) drug therapy remains a challenge. Dual modulation of dopamine and 5-HT receptors has emerged as a promising approach in anti-PD drug development. Taking advantage of the newly discovered aporphine analogue(s), (6aR)-11-amino-N-propyl-noraporphine (SOMCL-171), which ...

Glutamate receptors were studied in the brains of controls and Parkinson's disease (PD) patients, of which 10 of 14 developed motor complications (dyskinesias and/or wearing-off) following levodopa therapy. 125I-RTI binding to the dopamine transporter and dopamine concentrations show compar...

Dopamine denervation in Parkinson's disease and repeated Levodopa (L-DOPA) administration that induces dyskinesias are associated with an enhancement of basal ganglia neuropeptide transmission. Various adjunct non-dopaminergic treatments to Levodopa were shown to reduce and/or prevent dyski...

Fatty acids play a critical role in brain function but their specific role in the pathophysiology of Parkinson disease (PD) and levodopa-induced motor complications is still unknown. From a therapeutic standpoint, it is important to determine the relation between brain fatty acids and PD because...

A chiral lithium binaphtholate catalyzes the enantioselective amination of α-alkyl-β-keto esters with azodicarboxylates to produce optically active α,α-disubstituted α-amino acid derivatives in high yields and with good to high enantioselectivities. A stoichiometric amount of lithium hydrox...

The aim of this work was to carry out preliminary experiments for preparation of levodopa (LEVO)-containing intranasal powder. The experiments were designed according to the Quality by Design (QbD) concept. Based on prior risk assessment, LEVO and chitosan (CH) or sodium hyaluronate (HA) as muco...

This study aims to investigate the feasibility of Levodopa transdermal delivery systems (TDSs). Levodopa TDSs were formulated using various vehicles and permeation enhancers, and in vitro permeation and in vivo pharmacokinetic studies were carried out. In the in vitro study, ester-type vehicles ...