Search results for "Docking studies"
showing 4 items of 14 documents
Modeling of interactions between xenobiotics and cytochrome P450 (CYP) enzymes
2015
The adverse effects to humans and environment of only few chemicals are well known. Absorption, distribution, metabolism, and excretion (ADME) are the steps of pharmaco/toxicokinetics that determine the internal dose of chemicals to which the organism is exposed. Of all the xenobiotic-metabolizing enzymes, the cytochrome P450 (CYP) enzymes are the most important due to their abundance and versatility. Reactions catalyzed by CYPs usually turn xenobiotics to harmless and excretable metabolites, but sometimes an innocuous xenobiotic is transformed into a toxic metabolite. Data on ADME and toxicity properties of compounds are increasingly generated using in vitro and modeling (in silico) tools.…
Pyrrolomycins as antimicrobial agents. Microwave-assisted organic synthesis and insights into their antimicrobial mechanism of action
2019
Abstract New compounds able to counteract staphylococcal biofilm formation are needed. In this study we investigate the mechanism of action of pyrrolomycins, whose potential as antimicrobial agents has been demonstrated. We performed a new efficient and easy method to use microwave organic synthesis suitable for obtaining pyrrolomycins in good yields and in suitable amount for their in vitro in-depth investigation. We evaluate the inhibitory activity towards Sortase A (SrtA), a transpeptidase responsible for covalent anchoring in Gram-positive peptidoglycan of many surface proteins involved in adhesion and in biofilm formation. All compounds show a good inhibitory activity toward SrtA, havi…
Synthesis and Molecular Modeling Studies of Derivatives of a Highly Potent Peptidomimetic Vinyl Ester as Falcipain-2 Inhibitors
2012
Herein we report the synthesis of a set of constrained peptidomimetics endowed with an electrophilic vinyl ester warhead and structurally related to a previously identified lead compound, a potent and irreversible inhibitor of falcipain-2 (FP-2). FP-2 is the main hemoglobinase of the malaria parasite P. falciparum. The new compounds were evaluated for their inhibition against FP-2, and the results were rationalized on the basis of docking experiments. These studies underscore the pivotal role of both the ester function at the P1' site and the trifluoromethyl group of the P3 side chain in determining the correct orientation of the Michael acceptor warhead in the catalytic site, and as a cons…
Synthesis and Structure-Affinity Relationships of Spirocyclic Benzopyrans with Exocyclic Amino Moiety
2019
σ1 and/or σ2 receptors play a crucial role in pathological conditions such as pain, neurodegenerative disorders, and cancer. A set of spirocyclic cyclohexanes with diverse O-heterocycles and amino moieties (general structure III) was prepared and pharmacologically evaluated. In structure-activity relationships studies, the σ1 receptor affinity and σ1:σ2 selectivity were correlated with the stereochemistry, the kind and substitution pattern of the O-heterocycle, and the substituents at the exocyclic amino moiety. cis-configured 2-benzopyran cis-11b bearing a methoxy group and a tertiary cyclohexylmethylamino moiety showed the highest σ1 affinity ( Ki = 1.9 nM) of this series of compounds. In…