Chemical Biology & Drug Design

Many neurodegenerative diseases are thought to be caused by highly ordered, protein aggregates termed amyloids. The heterogeneity of amyloids creates challenges in determining their structure by typical methods. Rather, small molecules have proven to be powerful probes. Moreover, next generation amyloid ligands promise to provide insight into how distinct amyloid conformers contribute to disease.

Crystallography, molecular dynamics simulations, and structural analysis reveal a rare “expanded pocket” state key to drug design for undecaprenyl pyrophosphate synthase, an attractive target for anti-microbial therapy

Data are presented showing the inhibitory activity of two synthetic derivatives on the activity of an Antiproliferative Factor (APF) from patients with interstitial cystitis/painful bladder syndrome

Compstatin family peptides are potent inhibitors of the complement system and promising drug candidates against diseases involving under-regulated complement activation. The design of new compstatin variants is presented, together with SPR and ELISA characterisation.

A series of 2,3-dihydro-4H-pyridinone derivatives has been prepared and evaluated for antiviral activity. In the antiviral screening, several compounds showed to be fairly active against viruses belonging to the Flaviviridae family. Among these, three compouds (4a cis, 4c cis and 6a) showed an interesting activity against YFV, BVDV and HCV with an EC₅₀ in a low micromolar range

Prostate cancer is one of the most often diagnosed cancers in men and treated with androgen receptor (AR) antagonists. Derivatives of the natural compound anthranilic acid provide a novel scaffold for new AR antagonists that bind to the AR, inhibit the AR-mediated transactivation, the expression of the AR target gene PSA, and prostate cancer cell proliferation.

The downregulation of cyclin D-1 and ET-1, via NFκB inhibition, and the increase in NO, via Ca⁺⁺/eNOS, are responsible for growth arrest. The loss of ET-1 and the production of NO contribute to the Rottlerin anti-hypertensive effect.

The good correlation between experimental and calculated values of an endpoint for sub-training and calibration sets can be in fact a poor model

A spermine dinuclear palladium(II) complex (Pd₂-Spm) was synthesized and tested towards two human breast cancer cell lines (MCF-7 and MDA-MB-231) as to its antiproliferative properties, and compared to the widely used drug cisplatin (cDDP). For optimized concentrations Pd₂-Spm induced a rapid growth-inhibiting effect, as opposed to cDDP which seems to have a slower kinetics. The results evidence a possible distinct mechanism of action for these two Pt(II) complexes, which may explain their synergistic activity when co-administered.

The present article describes a series of twenty-one coumarine derivatives, which were synthesized and evaluated against Mycobacterium tuberculosis.

The inhibition effects of some natural phenolic derivatives such as resveratrol, catechin, silymarin, dobutamin, and curcumin were determined on human cytosolic carbonic anhydrase isozymes I and II. These natural product phenols had marked inhibitory effects and were generally found as competitive inhibitors with 4-nitrophenyl acetate substrate