Letters in Drug Design & Discovery - Volume 5, Issue 2, 2008

The present CoMFA study on thiazolidine-2,4-diones attempts to quantitatively describe the structural features of the compounds for high PPAR-γ agonistic action. A set of 50 compounds was used for the analysis. A training set and a test set were designed consisting of 39 and 11 compounds, respectively. All the molecules were modeled and energy minimized using SYBYL 6.7 software. The molecules were aligned using the mo Read More

This article presents a review on artepillin C, a diprenyl-p-hydroxycinnamic acid derivative mainly isolated from Baccharis species, and one of the principal phenolic acids present in Brazilian propolis, covering aspects of its occurrence, synthesis, biological activities and pharmacokinetics.

Bromo- and alkoxymethyl-furocoumarins were synthesized and evaluated for their ability to photoinduce cell death in human tumoral cell culture. Bromo substituted compounds resulted to be the most phototoxic compounds giving rise to a significant induction of apoptosis at 24 h from irradiation as demonstrated by a remarkable percentage of Annexin- V positive cells. The DNA photocleavaging properties of these deri Read More

Linear peptide analogs of complestatin were synthesized via solid phase peptide synthesis and tested in vitro as inhibitors against N-methyl-D-aspartic acid (NMDA) neurotoxicity as possible new peptidic neuroprotectants. While none of the analogs were as potent as the parent compound (IC50 = 2.5 μM), hexamer 11c and heptamer 1c, which contain all D-amino acids, showed modestly potent neuroprotective effects with I Read More

Four known small molecule uracil-DNA glycosylase (UNG) inhibitors were synthesized and tested against human melanoma cells, IgR3 and MM200. They were found to be effective against cell proliferation at micromolar concentrations and to operate through a nonapoptotic mechanism. Thus, small molecules that target UNG may be useful as potential chemotherapeutic agents against human melanoma.

In research for a new immunomodulator, we discoverd a novel hydroxypiperidine derivative 9h which was a potent inhibitor of IL-15induced T cell activation. Further modification of 9h gave a potent and orally active agent 10 which was effective in a mouse CIA model.

We have explored a series of spirocyclic piperidine amide derivatives with respect to the N-acyl portion (viz. 6) for inhibition of tryptase. Thus, we identified analogues 6nn and 6oo as potent tryptase inhibitors (IC50 < 10 nM) with excellent selectivity vs. trypsin. Other interesting compounds (IC50 = 10-20 nM) in this chemical series are 6k, 6m, 6ff, and 6bbb. X-ray co-crystal structures of 6nn•tryptase and 6pp•tryptase are reported.

Intramolecular N-7 alkylation of 6-substituted purines gave rise to a new series of tricyclic purine derivatives. The new compounds were evaluated for their cytotoxicity, their antileishmania activity together with their capacity to modulate NO production in macrophages. As a result compound 1 exhibited a modest activity against KB cells. On the other hand 4a was active against Leishmania and it diminished NO production of BC Read More

In this work we reported the design, synthesis and evaluation of the new diaryl heterocyclic derivatives based on the lead compounds of Rofecoxib and Celecoxib by application of the principle of isosterism. The in vivo pharmacological evaluation of these new compounds lead us to select the compounds (Ia) and (IIc) as a new prototype which a substituent ortho to the methylsulfone or sulfonamide group was introduced for fur Read More

Mycophenolate mofetil, an inosine monophosphate dehydrogenase inhibitor, that inhibits the de novo pathway of guanosine nucleotide synthesis, inhibits proliferative responses of T and B lymphocytes as well as antibody production by B-lymphocytes. It is indicated for the prophylaxis of organ rejection after allogeneic cardiac, hepatic and renal transplants. It has also been recently used with good success in patients with lupus Read More

The present article describes a series of eighteen N'-[(E)-(hydroxy, methoxy and ethoxy substitutedphenyl) methylidene]isonicotinohydrazide derivatives, which were synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis, and the activity expressed as the minimum inhibitory concentration (MIC) in μg/ml. Compounds 2a, 2d-f, and 2h exhibited a significant activity (0.31-1.25 Read More

Chemotherapeutic options for androgen-independent prostate cancer are extremely limited with minimum survival advantage. The benzyl-substituted unbridged titanocene bis-[(p-methoxybenzyl)cyclopentadienyl] titanium(IV) dichloride (Titanocene Y) was tested in vitro against the human prostate cancer androgen-independent cell, PC-3, which demonstrated an IC50 value of 56 x 10-6 mol/L compared to 5.6 x 10-6 Read More

The present investigation was focused on the effects induced by haloperidol and apomorphine on the antinociception induced by DAMGO (highly selective μ-agonist), U50-488H (highly selective k-agonist) and deltorphin II (highly selective δ-agonists). Haloperidol (a dopamine receptor antagonist) and apomorphine (a dopamine receptor agonist) (0.1-1.0-2.0 mg/kg/i.p.) per se did not change the pain threshold of mice bo Read More

Abdominal aortic surgery is relatively common associated with considerable postoperative morbidity and mortality. The aortic cross-clamping for the implantation of a vascular prosthetic graft induces a systemic inflammatory response (SIR) because of an ischemia-reperfusion (IR) injury. In our experimental models we have reported that propofol anesthesia, compared with sevoflurane, after IR modulates SIR and this effect Read More