Discovery of α-amylase and α-glucosidase dual inhibitors from NPASS database for management of Type 2 Diabetes Mellitus: A chemoinformatic approach.

Postprandial hyperglycemia, typical manifestation of Type 2 Diabetes Mellitus (T2DM), is associated with notable global morbidity and mortality. Preventing the advancement of this condition by delaying the rate of glucose absorption through inhibition of α-amylase and α-glucosidase enzymatic activities is of utmost importance. Finding a safe antidiabetic drug is essential since those that are currently on the market have drawbacks like unpleasant side effects.

Alkaloids Isolated from Vepris glandulosa with Antidiabetic Properties: An In Vitro and In Silico Analysis.

Diabetes is a major global health issue and as current treatments fail, the search for new antidiabetic drugs is crucial. This investigation, focusing on identifying potential antidiabetic compounds from the endangered plant species Vepris glandulosa, led to the isolation of two known alkaloids, choisyine acetate (1) and choisyine (2). The study established the in vitro inhibitory activities and in silico molecular interaction of the two alkaloids with α-amylase based on IC values, Linewaever-Burk/Dixon plot kinetic analyses and Molecular docking, respectively.

Ergostanes from the mushroom Trametes versicolor and their cancer cell inhibition: In vitro and in silico evaluation.

In this study, five steroid compounds were isolated from the fruiting bodies mushroom Trametes versicolor. The compounds, 9,19-cyclolanostane-3,29-diol (3), ergosta-7,22-dien-3-acetate (4), and ergosta-8(14),22-dien-3β,5α,6β,7α-tetrol (5), were identified from T. versicolor for the first time.

Analysis of Chemical Composition, Antioxidant Activity, and Toxicity of Essential Oil from Aubl (Myristicaceae).

Volatile oils or essential oils (EOs) were extracted from three samples (labeled as A, B, and C) in September 2018 and February 2019; the extraction process involved hydrodistillation of the leaves. The chemical compositions of the EOs were analyzed using gas chromatography-mass spectrometry (GC/MS). The volatile components were identified by comparing their retention indices and mass spectra with standard substances documented in the literature (ADAMS).

Rational Approach toward COVID-19's Main Protease Inhibitors: A Hierarchical Biochemoinformatics Analysis.

This study investigated the potential of selected compounds as inhibitors of SARS-CoV-2 M through pharmacokinetic and toxicological analyses, molecular docking, and molecular dynamics simulations. In silico molecular docking simulations revealed promising ligands with favorable binding affinities for M, ranging from -6.2 to -9.

Unveiling the Potential of -Kaurane Diterpenoids: Multifaceted Natural Products for Drug Discovery.

Natural products hold immense potential for drug discovery, yet many remain unexplored in vast libraries and databases. In an attempt to fill this gap and meet the growing demand for effective drugs, this study delves into the promising world of -kaurane diterpenoids, a class of natural products with huge therapeutic potential. With a dataset of 570 -kaurane diterpenoids obtained from the literature, we conducted an in silico analysis, evaluating their physicochemical, pharmacokinetic, and toxicological properties with a focus on their therapeutic implications.

Development of Potential Multi-Target Inhibitors for Human Cholinesterases and Beta-Secretase 1: A Computational Approach.

Alzheimer's disease causes chronic neurodegeneration and is the leading cause of dementia in the world. The causes of this disease are not fully understood but seem to involve two essential cerebral pathways: cholinergic and amyloid. The simultaneous inhibition of AChE, BuChE, and BACE-1, essential enzymes involved in those pathways, is a promising therapeutic approach to treat the symptoms and, hopefully, also halt the disease progression.

Analgesic Activity of 5-Acetamido-2-Hydroxy Benzoic Acid Derivatives and an In-Vivo and In-Silico Analysis of Their Target Interactions.

The design, synthesis, and evaluation of novel non-steroidal anti-inflammatory drugs (NSAIDs) with better activity and lower side effects are big challenges today. In this work, two 5-acetamido-2-hydroxy benzoic acid derivatives were proposed, increasing the alkyl position (methyl) in an acetamide moiety, and synthesized, and their structural elucidation was performed using H NMR and C NMR. The changes in methyl in larger groups such as phenyl and benzyl aim to increase their selectivity over cyclooxygenase 2 (COX-2).

Hierarchical Virtual Screening of Potential New Antibiotics from Polyoxygenated Dibenzofurans against Strains.

is a microorganism with high morbidity and mortality due to antibiotic-resistant strains, making the search for new therapeutic options urgent. In this context, computational drug design can facilitate the drug discovery process, optimizing time and resources. In this work, computational methods involving ligand- and structure-based virtual screening were employed to identify potential antibacterial agents against the MRSA and VRSA strains.

Therapeutic Potential of the Genus Phytochemicals: A Theoretical ADME/Tox Analysis.

Natural products (NPs) are essential in the search for new drugs to treat a wide range of diseases, including infectious and malignant disorders. However, despite the discovery of many bioactive NPs, they often do not make it to market as drugs due to toxicity and other challenges. The development of NPs into drugs is a long and expensive process, and many promising compounds are abandoned along the way.

Multivariate QSAR, similarity search and ADMET studies based in a set of methylamine derivatives described as dopamine transporter inhibitors.

The dopamine transporter (DAT), responsible for the regulation of dopaminergic neurotransmission, is implicated in the etiology of several neuropsychiatric disorders which, in turn, have contributed to high rates of disability and numerous deaths in recent years, significantly impacting the global health system. Although the research for new drugs for the treatment of neuropsychiatric disorders has evolved in recent years, the availability of DAT-selective drugs that do not generate the same psychostimulant effects observed in drugs of abuse remains scarce. Therefore, we performed a QSAR study based on a dataset of 36 methylamine derivatives described as DAT inhibitors.

Variation in the Chemical Composition of Endemic Specimens of J. Koenig from the Amazon and In Silico Investigation of the ADME/Tox Properties of the Major Compounds.

Four species of the genus can be found in Brazil. is a species endemic to India and Brazil. In this paper, we collected six specimens of for evaluation of their volatile chemical profiles.

In deep bioinformatic characterization of a novel fumarate hydratase variant FH c.199T > G; (p.Tyr67Asp) in hereditary leiomyomatosis and renal cell carcinoma.

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare, autosomal dominant tumor predisposition syndrome characterized by variable development of multiple skin and uterus leiomyomas and aggressive forms of renal cell carcinoma (RCC). Mutations in fumarate hydratase (FH), one of the proteins in homologous recombination repair, precede the development of HLRCC with high penetrance. Considering the risk of early metastasis of RCC, FH has been included in mutation screening panels.

Design and Identification of Inhibitors for the Spike-ACE2 Target of SARS-CoV-2.

When an epidemic started in the Chinese city of Wuhan in December 2019, coronavirus was identified as the cause. Infection by the virus occurs through the interaction of viral S protein with the hosts' angiotensin-converting enzyme 2. By leveraging resources such as the DrugBank database and bioinformatics techniques, ligands with potential activity against the SARS-CoV-2 spike protein were designed and identified in this investigation.

Pharmacological Characteristics of the Hydroethanolic Extract of (L) R. K. Jansen Flowers: ADME/Tox and Antihypertensive and Chronic Toxicity Evaluation.

(L.) R. K.

Inhibition Kinetics and Theoretical Studies on Engl. Dual Inhibitors of α-Glucosidase and α-Amylase.

Compounds from Engl. were previously reported for inhibitory activities of amylase and glucosidase enzymatic action on starch as a preliminary study toward the establishment of a management strategy against postprandial hyperglycemia, however, the inhibitory kinetics and molecular interaction of these compounds were never established. A study was thus designed to establish the inhibitory kinetics and in silico molecular interaction of α-glucosidase and α-amylase with metabolites based on Lineweaver-Burk/Dixon plot analyses and using Molecular Operating Environment (MOE) software, respectively.

Galantamine Based Novel Acetylcholinesterase Enzyme Inhibitors: A Molecular Modeling Design Approach.

Acetylcholinesterase (AChE) enzymes play an essential role in the development of Alzheimer's disease (AD). Its excessive activity causes several neuronal problems, particularly psychopathies and neuronal cell death. A bioactive pose on the AChE B site of the human acetylcholinesterase (AChE) enzyme employed in this investigation, which was obtained from the Protein Data Bank (PDB ID 4EY6), allowed for the prediction of the binding affinity and free binding energy between the protein and the ligand.

Antiplasmodial activity of coumarins isolated from : and studies.

is found in the Brazilian semiarid region. This specie is little chemically and biologically studied. spp.

Identification of a Novel Dual Inhibitor of Acetylcholinesterase and Butyrylcholinesterase: In Vitro and In Silico Studies.

The enhancement of cholinergic functions via acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition is considered a valuable therapeutic strategy for the treatment of Alzheimer's disease. This study aimed to evaluate the in vitro effect of ZINC390718, previously filtered using computational approaches, on both cholinesterases and to characterize, using a molecular dynamics (MD) simulation, the possible binding mode of this compound inside the cholinesterase enzymes. The in vitro cytotoxicity effect was also investigated using a primary astrocyte-enriched glial cell culture.

Hierarchical Virtual Screening and Binding Free Energy Prediction of Potential Modulators of Aedes Aegypti Odorant-Binding Protein 1.

The Aedes aegypti mosquito is the main hematophagous vector responsible for arbovirus transmission in Brazil. The disruption of A. aegypti hematophagy remains one of the most efficient and least toxic methods against these diseases and, therefore, efforts in the research of new chemical entities with repellent activity have advanced due to the elucidation of the functionality of the olfactory receptors and the behavior of mosquitoes.

Identification of Potential New Juvenile Hormone Inhibitors from N-Acyl Piperidine Derivatives: A Bioinformatics Approach.

mosquitoes transmit several human pathogens that cause millions of deaths worldwide, mainly in Latin America. The indiscriminate use of insecticides has resulted in the development of species resistance to some such compounds. Piperidine, a natural alkaloid isolated from , has been used as a hit compound due to its larvicidal activity against .

Identification of Potential Insect Growth Inhibitor against : A Bioinformatics Approach.

Aedes aegypti is the main vector that transmits viral diseases such as dengue, hemorrhagic dengue, urban yellow fever, zika, and chikungunya. Worldwide, many cases of dengue have been reported in recent years, showing significant growth. The best way to manage diseases transmitted by Aedes aegypti is to control the vector with insecticides, which have already been shown to be toxic to humans; moreover, insects have developed resistance.

A Computational Approach Applied to the Study of Potential Allosteric Inhibitors Protease NS2B/NS3 from Dengue Virus.

Dengue virus (DENV) is a danger to more than 400 million people in the world, and there is no specific treatment. Thus, there is an urgent need to develop an effective method to combat this pathology. NS2B/NS3 protease is an important biological target due it being necessary for viral replication and the fact that it promotes the spread of the infection.