Letters in Drug Design & Discovery - Volume 9, Issue 1, 2012

Letters in Drug Design and Discovery is now commencing its 9th year. It has grown over the years to become a reputable international journal widely known for rapidly publishing exciting new researches in the field. I look forward to receiving continued support from the Associate and Regional Editors as well as the Editorial Board Members whose constant help and guidance has been a major factor in its growth and popularity.

Two synthetic libraries based on a core isoxazoline motif have been designed and prepared specifically to probe the S1 and S4 binding pockets of the Factor Xa enzyme active sites. A highly efficient parallel solution phase synthetic method resulted in the synthesis of 3-arylisoxazoline-5-carboxamides and 3-arylisoxazoline-5-acetamides libraries yielding 192 compounds in total. Highlights of this work include preparation o Read More

This study evaluated the antioxidant activity of five resveratrol analogs by relating the activity of the molecule with its chemical structure. The five resveratrol analogs were synthesized and the antioxidant activity was evaluated using the DPPH method. The resveratrol was used as the reference standard. A descriptive statistical analysis and ANOVA followed by the Tukey test, with the aid of software. The antioxidant activity of res Read More

Three groups of distamycin analogues containing benzene units, potential minor groove binders, each containing six compounds, have been synthesized using Syncore Reactor. Ethidium bromide assay was used to show that these compounds bind to plasmid pBR322. The most active in fluorescence reduction appeared to be compounds with configuration meta-meta of benzene rings, formed library D.

The inhibition of Histamine N-methyltransferase (HNMT) has been recently shown to play potential roles in the treatment of neurodegenerative diseases, allergic vasoconstriction and anaphylactic manifestation. For designing and discovering new potential human HNMT inhibitors, the ligand (Hypo1) and structure-based (SB_Hypo1) pharmacophore models were developed based on the most active inhibitors and the highest re Read More

Fungi are some of the most neglected pathogens in terms of new drug discovery. Paracoccidioidomycosis, an endemic disease to South America, is caused by dimorphic fungi of Paracoccidioides genus. Reasonable citotoxicity, limited efficacy, and frequent use of current commercial antifungals have led to the emergence of resistance. Thus, the development of new antifungals with more selectivity and large spectrum of action i Read More

A series of aminoalkanol and amino acid derivatives of trans-cinnamic acid as well as aminoalkanol derivatives of α-phenylcinnamic acid was synthesized and evaluated for anticonvulsant activity. All compounds were verified in mice after intraperitoneal (i.p.) administration in maximal electroshock (MES) and subcutaneous pentetrazole (ScMet) induced seizures as well as neurotoxicity assessment. Six of them showed pr Read More

In continuation of our program to find compounds with potent anti-human immunodeficiency virus type 1 (HIV-1) activities, seventeen 5,6-dihydro-indolo[1,2-a]quinoxaline derivatives (1-17) were preliminarily evaluated as HIV-1 inhibitors in vitro. Among all the derivatives, especially compounds 10 and 17 showed the most potent anti-HIV-1 activities with EC50 values of 2.42 and 3.39 μg/mL, and TI values of 63.76 and 53.60, respectively.

There is an obvious need to develop efficient countermeasure agents for use in emergency situations or as adjuncts to radiotherapy to protect healthy tissues from the consequences of an irradiation. To this end, we have investigated the capacity of norbadione A, a polyphenol extracted from the edible mushroom Bay boletus to reduce the toxicity of ionizing radiation towards cultured cells and whole-body exposed mice. Read More

Docking of lobeline, a partial agonist of nicotinic acetylcholine receptors (nAChRs), was investigated at once into crystallographic structures of acetylcholine binding proteins (AChBP) and into α7 and α4β2 nAChRs homology models, and compared to behavior of full agonists, nicotine and epibatidine. The homology models were built using as templates the different pocket geometries established in crystallographic AChBP s Read More

Some novel thiazolylhydrazinomethylideneferrocenes 4 and 5 bearing phenyl and coumarin analogues respectively at position-4 of 1,3-thiazole were synthesized using established procedures and were evaluated for their in vitro antibacterial activity against four pathogenic bacterial strains namely, S. aureus, B. subtilis (Gram-positive), E. coli, P. aeruginosa (Gram-negative), and in vitro antifungal activity against two pathoge Read More

We report the use of sulfonate derivatives of estrone (E1) in the search for inhibitors of 17β-hydroxysteroid dehydrogenase, in particular, type 3 (17β-HSD3). Results suggest that the compounds are excellent inhibitors of 17β- HSD3 and a number were found to be extremely potent in comparison to the standard inhibitors used.

I describe a case of tachyphylaxis to pramipexole and its management in a patient with bipolar I disorder.

In order to improve the metabolic stability and bioavailability of scutellarin, some derivatives of its main metabolite (scutellarein) were designed and synthesized. The antioxidant activities of these target products were assessed by measuring its scavenging capacities toward DPPH and the protective effects on H2O2-induced cytotoxicity in PC12 cells. The results showed that the target compound 7g had a higher antioxidant Read More

Tyrosine kinases are important mediators of the signaling cascade, determining key roles in diverse biological processes like growth, differentiation, metabolism and apoptosis in response to external and internal stimuli. Recent advances have implicated the role of tyrosine kinases in the pathophysiology of cancer. Though their activity is tightly regulated in normal cells, they may acquire transforming functions due to mut Read More