Caffeic Acid Enhances the Anti-Leukemic Effect of Imatinib on Chronic Myeloid Leukemia Cells and Triggers Apoptosis in Cells Sensitive and Resistant to Imatinib.

Among the phenolic acids tested on the K562 cell line, a model of chronic myeloid leukemia (CML), caffeic acid (CA) was biologically active on sensitive and imatinib (IM)-resistant cells at micro-molar concentration, either in terms of reduction of cell proliferation or triggering of apoptosis. The CA treatment provoked mitochondrial membrane depolarization, genomic DNA fragmentation and phosphatidylserine exposure, hallmarks of apoptosis. Cell cycle analysis following the treatment with comparable cytotoxic concentrations of IM or CA showed marked differences in the distribution profiles.

A comprehensive review on tyrosinase inhibitors.

Tyrosinase is a multi-copper enzyme which is widely distributed in different organisms and plays an important role in the melanogenesis and enzymatic browning. Therefore, its inhibitors can be attractive in cosmetics and medicinal industries as depigmentation agents and also in food and agriculture industries as antibrowning compounds. For this purpose, many natural, semi-synthetic and synthetic inhibitors have been developed by different screening methods to date.

Ab initio molecular simulations for proposing potent inhibitors to butyrylcholinesterases.

Butyrylcholinesterase (BChE) exists mainly at neuromuscular junctions and plays an important role in the hydrolyzing mechanism of neurotransmitter acetylcholine. A variety of compounds have been produced in order to inhibit the function of BChE. We here investigate the specific interactions between BChE and some ligands (Kx) with large binding affinity to BChE, using ligand-docking, classical molecular mechanics and ab initio fragment molecular orbital (FMO) methods.

A rational workflow for sequential virtual screening of chemical libraries on searching for new tyrosinase inhibitors.

The tyrosinase is a bifunctional, copper-containing enzyme widely distributed in the phylogenetic tree. This enzyme is involved in the production of melanin and some other pigments in humans, animals and plants, including skin pigmentations in mammals, and browning process in plants and vegetables. Therefore, enzyme inhibitors has been under the attention of the scientist community, due to its broad applications in food, cosmetic, agricultural and medicinal fields, to avoid the undesirable effects of abnormal melanin overproduction.

Flavonoid derivatives as potent tyrosinase inhibitors - a survey of recent findings between 2008-2013.

Tyrosinase (EC 1.14.18.

Tyrosinase enzyme: 1. An overview on a pharmacological target.

The tyrosinase enzyme (EC 1.14.18.

Dipeptide inhibitors of thermolysin and angiotensin I-converting enzyme.

Thermolysin (TLN) and other thermolysin-like zinc metalloproteinases (TLPs),are important virulence factors for pathogenesis of bacterial infections by suppressing the innate immune system of the host. Therapeutic inhibition ofTLPs is believed to be a novel strategy inthe development of a new generation antibiotics.In the present study inhibition of TLN and angiotensin I-converting enzyme (ACE) by small peptides were studied by in vitro binding assays and theoretical calculations.

Genome analysis of the new human polyomaviruses.

Polyomaviridae is a growing family of naked, double-stranded DNA viruses that infect birds and mammals. The last few years, several new members infecting birds or primates have been discovered, including seven human polyomaviruses: KI, WU, Merkel cell polyomavirus, HPyV6, HPyV7, trichodysplasia spinulosa-associated polyomavirus, and HPyV9. In addition, DNA and antibodies against the monkey lymphotropic polyomavirus have been detected in humans, indicating that this virus can also infect man.

Structure-based analysis of the molecular recognitions between HIV-1 TAR-RNA and transcription factor nuclear factor-kappaB (NFkB).

In this paper we applied the "macromolecular docking" procedure to perform molecular modeling with the aim of screening transcription factor sequences for possible interaction to the HIV-1 TAR-RNA, employing the software Hex version 4.2. The molecular modeling data were compared with electrophoretic mobility shift assays (EMSA) and surface plasmon resonance (SPR) based biospecific interaction analysis (BIA) using an optical biosensor.

Specific interactions and binding energies between thermolysin and potent inhibitors: molecular simulations based on ab initio molecular orbital method.

Biochemical functions of the metalloprotease thermolysin (TLN) are controlled by various inhibitors. In a recent study we identified 12 compounds as TLN inhibitors by virtual screening and in vitro competitive binding assays. However, the specific interactions between TLN and these inhibitors have not been clarified.

Specific interactions and binding free energies between thermolysin and dipeptides: molecular simulations combined with ab initio molecular orbital and classical vibrational analysis.

Thermolysin (TLN) is a metalloprotease widely used as a nonspecific protease for sequencing peptide and synthesizing many useful chemical compounds by the chemical industry. It was experimentally shown that the activity and functions of TLN are inhibited by the binding of many types of amino acid dipeptides. However, the binding mechanisms between TLN and dipeptides have not been clarified at the atomic and electronic levels.

BK virus-associated infection in cerebrospinal fluid of neurological patients and mutation analysis of the complete VP1 gene in different patient groups.

While BK virus (BKV) is frequently associated with pathological conditions in bone marrow and renal transplant recipients, BKV infection in neurological individuals has been rarely reported. As a result of a BKV, JCV, and SV40 large T antigen-specific multiplex PCR on 2,062 cerebrospinal fluid (CSF) samples from neurological patients suspicious of JCV infection, we identified 20 subjects with at least 1 CSF specimen positive for BKV large T antigen DNA. Because VP1 protein has been suggested to influence the biological/pathological properties of BKV, we tried to sequence the entire VP1 gene in the BKV-positive neurological patients and succeeded in 14 of the 20 neurological patients.

Alpha-glucosidase and tyrosinase inhibitors from fungal hydroxylation of tibolone and hydroxytibolones.

Sixteen new and one known metabolites 4-20 were obtained by incubation of tibolone (1) and hydroxytibolones (2 and 3) with various fungi. Their structures were elucidated by means of a homo and heteronuclear 2D NMR and by HREI-MS techniques. The relative stereochemistry was deduced by 2D NOESY experiment.

Ligand-based computer-aided discovery of tyrosinase inhibitors. Applications of the TOMOCOMD-CARDD method to the elucidation of new compounds.

In this review an overview of the application of computational approaches is given. Specifically, the uses of Quantitative Structure-Activity Relationship (QSAR) methods for in silico identification of new families of compounds as novel tyrosinase inhibitors are revised. Assembling, validation of models through prediction series, and virtual screening of external data sets are also shown, to prove the accuracy of the QSAR models obtained with the TOMOCOMD-CARDD (TOpological MOlecular COMputational Design-Computer-Aided Rational Drug Design) software and Linear Discriminant Analysis (LDA) as statistical technique.

The diterpenoid alkaloid noroxoaconitine is a Mapkap kinase 5 (MK5/PRAK) inhibitor.

The mitogen-activated protein kinase-activated protein kinase MK5 is ubiquitously expressed in vertebrates and is implicated in cell proliferation, cytoskeletal remodeling, and anxiety behavior. This makes MK5 an attractive drug target. We tested several diterpenoid alkaloids for their ability to suppress MK5 kinase activity.

Identification of novel quinazolin-4(3H)-ones as inhibitors of thermolysin, the prototype of the M4 family of proteinases.

A combinatorial series of novel quinazolin-4(3H)-ones were synthesised and their structures were established based on spectroscopic data (IR, NMR, EI-MS, and FAB-MS). The compounds were tested for inhibition of the zinc metalloproteinase thermolysin (TLN) utilizing a chemical array-based approach. Some of the compounds were found to inhibit TLN, with IC(50) values ranging from 0.

Tyrosinase inhibitory effect of benzoic acid derivatives and their structure-activity relationships.

A series of benzoic acid derivatives 1-10 have been synthesised by two different methods. Compounds 1-6 were synthesised by a facile procedure for esterification using N,N'-dicyclohexylcarbodiimide (DCC) as a coupling agent, methylene chloride as a solvent system and dimethylaminopyridine (DMAP). While 7-10 were synthesised by converting benzoic acid into benzoyl chloride by treating with thionyl chloride in the presence of benzene and performing a further reaction with amine in dried benzene.

Predictions of the ADMET properties of candidate drug molecules utilizing different QSAR/QSPR modelling approaches.

The integration of early ADMET (absorption, distribution, metabolism, excretion and toxicity) profiling, or simply prediction, of 'lead' molecules to speed-up the 'lead' selection further for phase-I trial without losing large amount of revenue. The ADMET profiling and prediction is mostly dependent of a number of molecular descriptors, for example, Lipinski's 'Rule of 5' (Ro5). Recently a large number of articles have been reporting that it possible to do some prediction of the ADMET properties using the structural features of the molecules, utilizing several and multiple approaches.

Determinants for psychrophilic and thermophilic features of metallopeptidases of the M4 family.

Naturally occurring peptidases from organisms living under extreme conditions are adapted to function in environmental extremes, including temperature, salinity, pH, or pressure. These organisms represent unique sources for new bio-molecules that have both industrial and medicinal application. Adaptive strategies for functioning under extreme conditions are reflected at the enzyme sequence and structural level.

Cholinesterase inhibitory activities of some flavonoid derivatives and chosen xanthone and their molecular docking studies.

Flavonoids are one of the largest classes of plant secondary metabolites and are known to possess a number of significant biological activities for human health. In this study, we examined in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of four flavonoid derivatives--quercetin, rutin, kaempferol 3-O-beta-D-galactoside and macluraxanthone. The in vitro results showed that quercetin and macluraxanthone displayed a concentration-dependant inhibition of AChE and BChE.

Molecular interactions of cholinesterases inhibitors using in silico methods: current status and future prospects.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a low amount of acetylcholine (ACh) in hippocampus and cortex. Acetylcholinesterase (AChE) is one of the most important enzymes in many living organisms including human being and other vertebrates, insects like mosquitoes, among others. Several reports have been published where it has been clearly shown that the genesis of amyloid protein plaques associated with AD is connected to modifications of both AChE and butyrylcholinesterase (BChE), since the plaque is significantly decreased in AD patients using cholinesterase inhibitors (ChEIs).

Recent advancements for the evaluation of anti-viral activities of natural products.

Significant progress has been achieved for the development of novel anti-viral drugs in the recent years. Large numbers of these newly developed drugs belong to three groups of compounds, nucleoside analogues, thymidine kinase-dependent nucleotide analogues and specific viral enzyme inhibitors. It has been found that the natural products, like plant extract, plant-derived compounds (phytochemicals) and so on, as well as traditional medicines, like Ayurvedic, traditional Chinese medicine (TCM), Chakma medicines and so on, are the potential sources for potential and novel anti-viral drugs based on different in vitro and in vivo approaches.