Introduction: Even though there have been substantial advances in our understanding of biological systems, research drug discovery is only just now beginning to utilize this type information. The single-target paradigm, which exemplifies the reductionist approach, remains a mainstay today. A deeper view complexity involved necessary advance on field.Areas covered: This perspective provides summary areas where cheminformatics has played key role discovery, including available resources as...

Natural products are an invaluable source of molecules with a large variety biological activities. Interest in natural drug discovery is documented increasing number publications bioactive secondary metabolites. Among those, medicinal plants one the most studied for this endeavor. An ever thriving area opportunity within field concerns antidiabetic products. As result, vast amount metabolites isolated from used against diabetes mellitus but whose information has not been organized...

Abstract Secondary metabolites, commonly referred to as natural products, are produced by living organisms and usually have pharmacological or biological activities. metabolites the primary source for discovery of new drugs. Furthermore, secondary also used food preservatives, biopesticides research tools. Although mainly their beneficial activity, toxicity some them may limit use. The assessment any compound that is prone be in direct contact with human beings vital importance. There a vast...

Extensive fractionation of an extract from the grain-based culture endophytic fungus Preussia minimoides led to isolation two new polyketides with novel skeletons, minimoidiones A (1) and B (2), along known compounds preussochromone C (3), corymbiferone (4), 5-hydroxy-2,7-dimethoxy-8-methylnaphthoquinone (5). The structures 1 2 were elucidated using 1D 2D NMR data analysis, DFT calculations 1H chemical shifts. absolute configuration was established by a single-crystal X-ray diffraction...

A new malbrancheamide analogue, isomalbrancheamide B (3), along with three known compounds, (1), (2), and premalbrancheamide (4), were isolated in higher yields from the alkaloid fraction of fungus Malbranchea aurantiaca. The interaction alkaloids 1–4 calmodulin (CaM) was analyzed using different enzymatic, fluorescence, spectroscopic, nuclear magnetic resonance (NMR), molecular modelling techniques. On basis enzymatic fluorescence experiments, malbrancheamides 1–3 are classical CaM...

From an extract prepared from the grain-based culture of Malbranchea flavorosea two new polyketides, namely, 8-chloroxylarinol A (1) and flavoroseoside (2), along with known compounds xylarinol (3), B (4), massarigenins C (5 6), clavatol (7), were isolated. The structures 1 2 elucidated using spectroscopic methods corroborated by single-crystal X-ray diffraction analysis. In case compound absolute configuration at stereogenic centers was established according to method Flack. addition,...

Bioassay-guided fractionation of an extract prepared from the culture medium and mycelium Purpureocillium lilacinum allowed isolation two calmodulin (CaM) inhibitors, namely, acremoxanthone C (1) acremonidin A (2). The absolute configuration 1 was established as 2R, 3R, 1′S, 11′S, 14′R through extensive NMR spectroscopy molecular modeling calculations at DFT B3LYP/DGDZVP level, which included comparison between theoretical experimental specific rotation, 3JC,H, 3JH,H values. Compounds 2 bind...

The purpose of this research was to examine the preclinical efficacy a decoction from roots Acourtia thurberi as hypoglycemic, antihyperglycemic, and antihyperalgesic agent using well-known experimental models in mice. Acute oral administration A. did not produce toxic effects mice, according Lorke procedure. (31.6-316.2 mg/kg, p. o.) decreased blood glucose levels during acute hypoglycemic tolerance sucrose tests, both normoglycemic hyperglycemic animals. Phytochemical analysis led...

In order to contribute the structural basis for rational design of calmodulin (CaM) inhibitors, we analyzed interaction CaM with 14 classic antagonists and two compounds that do not affect CaM, using docking molecular dynamics (MD) simulations, data were compared available experimental data. The Ca(2+)-CaM-Ligands complexes simulated 20 ns, starting in "open" "closed" conformations. analysis MD simulations provided insight into conformational changes undergone by during its these ligands....

Chagas disease affects 8–11 million people worldwide, most of them living in Latin America. Moreover, migratory phenomena have spread the infection beyond endemic areas. Efforts for development new pharmacological therapies are paramount as profile two marketed drugs currently available, nifurtimox and benznidazole, needs to be improved. Cruzain, a parasitic cysteine protease, is one attractive biological targets due its roles parasite survival immune evasion. In this work, we compiled...

Abstract Objectives This study was conducted to evaluate the vasorelaxant effect of fungal alkaloids malbrancheamides on pre-contracted rat aorta rings. Also, we explored probable mode action using experimental and theoretical docking studies. Methods The assessed rings with noradrenaline (0.1 μm). mechanism evaluated different inhibitors pathways involved in vasorelaxation process, such as l-NAME, indomethacin, tetraethylammonium atropine. analyses were carried out AutoDock 4.2 software...

Seven cyclotetradepsipeptides, namely beauverolides C (1), F (2), I (3), Ja (4), L (5), M (6), and N (7), were isolated from the entomopathogenic fungus Isaria fumosorosea. The evaluated as potential calmodulin (CaM) inhibitors using newly designed CaM biosensor hCaM M124C-AF350; these peptides displayed high affinity to protein with dissociation constants (Kd) ranging 0.078 μM 3.44 μM. Beauverolide Ja, only one containing a tryptophan residue in its structure, showed highest affinity....

Mammea-type coumarins are a particular type of secondary metabolites biosynthesized by the tropical rainforest tree Calophyllum Brasiliense, which is distributed from South America to Mexico. Particularly, mammea A/BA and A/BB (alone or as mixture) possess biological properties such cytotoxic antitumoral activities, however, most its molecular targets remain unknown. In this context, novel bioinformatic approaches, network pharmacology analysis, have been successfully used in herbal medicine...

Protein–protein interactions play central roles in physiological and pathological processes. The bases of the mechanisms drug action are relevant to discovery new therapeutic targets. This work focuses on understanding protein–protein–ligands complexes, using proteins calmodulin (CaM), human calcium/calmodulin‐dependent 3′,5′‐cyclic nucleotide phosphodiesterase 1A active (PDE1A), myosin light chain kinase (MLCK) ligands αII–spectrin peptide (αII–spec), two inhibitors CaM (chlorpromazine...

Abstract G-protein-biased agonism of the mu-opioid receptor (μ-OR) is emerging as a promising strategy in analgesia. A deep understanding how biased agonists modulate and differentiate G-protein-coupled receptors (GPCR) signaling pathways this transferred into cell are open questions. Here, using extensive all-atom molecular dynamics simulations, we analyzed binding recognition process effects three prototype μ-OR agonists. Our suggested structural mechanism involves an allosteric sodium ion...

Pesticides classified by mode of action as a source predictive models toxicity.

This work aimed to discover protein tyrosine phosphatase 1B (PTP1B) inhibitors from a small molecule library of natural products (NPs) derived selected Mexican medicinal plants and fungi find new hits for developing antidiabetic drugs. The showing similar IC50 values ursolic acid (UA) (positive control, = 26.5) were considered hits. These compounds canophyllol (1), 5-O-(β-D-glucopyranosyl)-7-methoxy-3',4'-dihydroxy-4-phenylcoumarin (2), 3,4-dimethoxy-2,5-phenanthrenediol (3), masticadienonic...

Abstract The prediction of toxicological endpoints has gained broad acceptance; it is widely applied in early stages drug discovery as well for impurities obtained the production generic or equivalent products. In this work, we describe methodologies compounds, with a particular focus on secondary metabolites. Case studies include toxicity natural compound databases anti-diabetic, anti-malaria and anti-HIV properties.