New evidence for tamoxifen as an antischistosomal agent: , and target fishing studies.

Praziquantel is the only drug available to treat schistosomiasis, and there is an urgent demand for new anthelmintic agents. We conducted in-depth and  studies and report a target fishing investigation. , tamoxifen was active against adult and immature worms at low concentrations (<5 μM).

Polygodial, a sesquiterpene isolated from Drimys brasiliensis (Winteraceae), triggers glucocorticoid-like effects on pancreatic β-cells.

Despite its common use, the synthetic glucocorticoid dexamethasone can cause several adverse effects, such as diabetes and insulin-related metabolic impairment. Thus, research on molecules that could provide the same anti-inflammatory response with milder side effects is constant. In this work the anti-inflammatory activity of the natural sesquiterpene polygodial, extracted from the endemic Brazilian plant Drimys brasiliensis Miers (Winteraceae), was investigated.

Theoretical studies of the role of C-terminal cysteines in the process of S-nitrosylation of human Src kinases.

Src tyrosine kinases are a family of non-receptor proteins that are responsible for the growth process, cellular proliferation, differentiation and survival. Lack of Src kinase control has been associated with the development of certain human cancers. This family of proteins is constituted of four domains, with SH1 being the kinase or catalytic domain.

Molecular modeling study on the disassembly of dendrimers designed as potential antichagasic and antileishmanial prodrugs.

A molecular modeling study was carried out to investigate the most likely enzymatic disassembly mechanism of dendrimers that were designed as potential antichagasic and antileishmanial prodrugs. The models contained myo-inositol (core), L-malic acid (spacer), and active agents such as 3-hydroxyflavone, quercetin, and hydroxymethylnitrofurazone (NFOH). A theoretical approach that considered one, two, or three branches has already been performed and reported by our research group; the work described herein focused on four (models A and B), five, or six branches, and considered their physicochemical properties, such as spatial hindrance, electrostatic potential mapping, and the lowest unoccupied molecular orbital energy (E(LUMO)).

Molecular modeling approach to predict a binding mode for the complex methotrexate-carboxypeptidase G2.

Carboxypeptidase G(2) (CPG(2)) is a zinc-metalloenzyme employed in a range of cancer chemotherapy strategies by activating selectively nontoxic prodrugs into cytotoxic drugs in tumor as well as in the treatment of intoxication caused by high-doses of the anticancer drug methotrexate (MTX). CPG(2) catalyzes the hydrolytic cleavage of C-terminal of glutamate moiety from folic acid and analogues. Regardless of its extensive application, its mechanism of catalysis has not yet been determined and, so far, no co-crystallized complex has been published.

New antitumoral agents I: In vitro anticancer activity and in vivo acute toxicity of synthetic 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadien-3-one and derivatives.

This paper describes a new method for the preparation of 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadien-3-one 1 and its derivatives 2-5. This set of synthetic compounds exhibited high antitumoral activities regarding in vitro screening against several human tumor cell lines as lung carcinoma NCI-460, melanoma UACC-62, breast MCF-7, colon HT-29, renal 786-O, ovarian OVCAR-03 and ovarian expressing the resistance phenotype for adriamycin NCI-ADR/RES, prostate PC-3, and leukemia K-562. Compounds were also tested against murine tumor cell line B16F10 melanoma and lymphocytic leukemia L1210 as well as to their effect toward normal macrophages.

Antileishmanial activity screening of 5-nitro-2-heterocyclic benzylidene hydrazides.

A series of 53 nitro derivatives rationally designed were obtained by parallel synthesis and screened against Leishmania donovani. Six compounds exhibited IC(50) values lower than standard drugs. Brief SAR analysis revealed that substitution is important to the activity.

Prodrugs for the treatment of neglected diseases.

Recently, World Health Organization (WHO) and Medicins San Frontieres (MSF) proposed a classification of diseases as global, neglected and extremely neglected. Global diseases, such as cancer, cardiovascular and mental (CNS) diseases represent the targets of the majority of the R&D efforts of pharmaceutical companies. Neglected diseases affect millions of people in the world yet existing drug therapy is limited and often inappropriate.

A new monoclinic polymorph of methyl p-aminobenzoate.

Single crystals of methyl-p-aminobenzoate (MAB), C(8)H(9)NO(2), were obtained during the synthesis of 4-amino-N'-(5-nitro-2-thienylmethylene)benzohydrazide. A P2(1)/c polymorph [a = 8.5969 (4) A, b = 5.

Potential tuberculostatic agents. Topliss application on benzoic acid [(5-nitro-thiophen-2-yl)-methylene]-hydrazide series.

Nitroaromatic compounds such as nifuroxazide are used in many human enteropathogenic bacteria infections without causing an increase in the plasmidial antibiotic resistance of the aerobic Gram-negative intestinal Enterobacteriaceae. For these reasons, these compounds have been synthesized using the rational approach of Topliss' decision tree. Generally, this approach allows us to obtain the most active derivative from the series in a few steps.