Targeting bacterial growth in biofilm conditions: rational design of novel inhibitors to mitigate clinical and food contamination using QSAR.

Antimicrobial resistance (AMR) is a pressing global issue exacerbated by the abuse of antibiotics and the formation of bacterial biofilms, which cause up to 80% of human bacterial infections. This study presents a computational strategy to address AMR by developing three novel quantitative structure-activity relationship (QSAR) models based on molecular topology to identify potential anti-biofilm and antibacterial agents. The models aim to determine the chemo-topological pattern of Gram (+) antibacterial, Gram (-) antibacterial, and biofilm formation inhibition activity.

Rational Design of a Potential New Nematicide Targeting Chitin Deacetylase.

In a previously published study, the authors devised a molecular topology QSAR (quantitative structure-activity relationship) approach to detect novel fungicides acting as inhibitors of chitin deacetylase (CDA). Several of the chosen compounds exhibited noteworthy activity. Due to the close relationship between chitin-related proteins present in fungi and other chitin-containing plant-parasitic species, the authors decided to test these molecules against nematodes, based on their negative impact on agriculture.

Elucidating the mechanism of action of mycotoxins through machine learning-driven QSAR models: Focus on lipid peroxidation.

Understanding the mechanisms of mycotoxin toxicity is crucial for establishing effective guidelines and preventive strategies. In this study, machine learning models based on quantitative structure-activity relationship (QSAR) were employed to predict the lipid peroxidation activity of mycotoxins. Two different algorithms using Linear Discriminant Analysis (LDA) and Artificial Neural Networks (ANNs) have been trained using a dataset of 70 mycotoxins.

Drug screening of α-amylase inhibitors as candidates for treating diabetes.

In the present study, the identification of potential α-amylase inhibitors is explored as a potential strategy for treating type-2 diabetes mellitus. A computationally driven approach using molecular docking was employed to search for new α-amylase inhibitors. The interactions of potential drugs with the enzyme's active site were investigated and compared with the contacts established by acarbose (a reference drug for α-amylase inhibition) in the crystallographic structure 1B2Y.

Rational Design of Chitin Deacetylase Inhibitors for Sustainable Agricultural Use Based on Molecular Topology.

Fungicide resistance is a major concern in modern agriculture; therefore, there is a pressing demand to develop new, greener chemicals. Chitin is a major component of the fungal cell wall and a well-known elicitor of plant immunity. To overcome chitin recognition, fungal pathogens developed different strategies, with chitin deacetylase (CDA) activity being the most conserved.

COVID-19 and the Importance of Being Prepared: A Multidisciplinary Strategy for the Discovery of Antivirals to Combat Pandemics.

During an emergency, such as a pandemic in which time and resources are extremely scarce, it is important to find effective and rapid solutions when searching for possible treatments. One possibility in this regard is the repurposing of available “on the market” drugs. This is a proof of the concept study showing the potential of a collaboration between two research groups, engaged in computer-aided drug design and control of viral infections, for the development of early strategies to combat future pandemics.

How Molecular Topology Can Help in Amyotrophic Lateral Sclerosis (ALS) Drug Development: A Revolutionary Paradigm for a Merciless Disease.

Even if amyotrophic lateral sclerosis is still considered an orphan disease to date, its prevalence among the population is growing fast. Despite the efforts made by researchers and pharmaceutical companies, the cryptic information related to the biological and physiological onset mechanisms, as well as the complexity in identifying specific pharmacological targets, make it almost impossible to find effective treatments. Furthermore, because of complex ethical and economic aspects, it is usually hard to find all the necessary resources when searching for drugs for new orphan diseases.

Macrolides May Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Entry into Cells: A Quantitative Structure Activity Relationship Study and Experimental Validation.

The global pandemic caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is threatening the health and economic systems worldwide. Despite the enormous efforts of scientists and clinicians around the world, there is still no drug or vaccine available worldwide for the treatment and prevention of the infection. A rapid strategy for the identification of new treatments is based on repurposing existing clinically approved drugs that show antiviral activity against SARS-CoV-2 infection.

Molecular Topology QSAR Strategy for Crop Protection: New Natural Fungicides with Chitin Inhibitory Activity.

Nowadays, crop protection is a major concern and how to proceed is a delicate point of contention. New products must be safe and ecofriendly in accordance with the actual legislation. In this context, we present a quantitative structure-activity relationship strategy based on molecular topology as a tool for generating natural products as potential fungicides following a mechanism of action based on the synthesis of chitin inhibition (chitinase inhibition).

What place does molecular topology have in today's drug discovery?

Introduction: Most methods in molecular and drug design are currently based on physicochemical descriptors. However, molecular topology, which relies on topological descriptors, has also shown value for molecular design even if it does not take into account the physical or chemical properties of ligands and receptors, including the ligand-receptor interaction itself.

Areas Covered: Herein, the authors provide new insights into the importance of molecular topology according to some of the latest discoveries in physics and chemistry.

Identification of New Templates for the Synthesis of BEA, BEC, and ISV Zeolites Using Molecular Topology and Monte Carlo Techniques.

The presence of organic structure directing agents (templates) in the synthesis of zeolites allows the synthesis to be directed, in many cases, toward structures in which there is a large stabilization between the template and the zeolite micropore due to dispersion interactions. Although other factors are also important (temperature, pH, Si/Al ratio, etc.), systems with strong zeolite-template interactions are good candidates for an application of new computational algorithms, for instance those based in molecular topology (MT), that can be used in combination with large databases of organic molecules.

DesMol2, an Effective Tool for the Construction of Molecular Libraries and Its Application to QSAR Using Molecular Topology.

A web application, DesMol2, which offers two main functionalities, is presented: the construction of molecular libraries and the calculation of topological indices. These functionalities are explained through a practical example of research of active molecules to the formylpeptide receptor (FPR), a receptor associated with chronic inflammation in systemic amyloidosis and Alzheimer's disease. Starting from a data(base) of 106 dioxopiperazine pyrrolidin piperazine derivatives and their respective constant values of binding affinity to FPR, multilinear regression and discriminant analyses are performed to calculate several predictive topological-mathematical models.

Molecular topology and QSAR multi-target analysis to boost the in silico research for fungicides in agricultural chemistry.

The aim of the present study is to show how molecular topology can be a powerful in silico tool for the prediction of the fungicidal activity of several diphenylamine derivatives against three fungal species (cucumber downy mildew, rice blast and cucumber gray mold). A multi-target QSAR model was developed, and two strategies were followed. First is the construction of a virtual library of molecules using DesMol2 program and a subsequent selection of potential active ones.

Alzheimer: A Decade of Drug Design. Why Molecular Topology can be an Extra Edge?

Background: The last decade was characterized by a growing awareness about the severity of dementia in the field of age-related and no age-related diseases and about the importance to invest resources in the research of new, effective treatments. Among the dementias, Alzheimer's plays a substantial role because of its extremely high incidence and fatality. Several pharmacological strategies have been tried but still now, Alzheimer keeps being an untreatable disease.

Molecular topology: A new strategy for antimicrobial resistance control.

The control of antimicrobial resistance (AMR) seems to have come to an impasse. The use and abuse of antibacterial drugs has had major consequences on the genetic mutability of both pathogenic and nonpathogenic microorganisms, leading to the development of new highly resistant strains. Because of the complexity of this situation, an in silico strategy based on QSAR molecular topology was devised to identify synthetic molecules as antimicrobial agents not susceptible to one or several mechanisms of resistance such as: biofilms formation (BF), ionophore (IA) activity, epimerase (EI) activity or SOS system (RecA inhibition).

Molecular topology: a strategy to identify novel compounds against ulcerative colitis.

In the present paper, a strategy to identify novel compounds against ulcerative colitis (UC) by molecular topology (MT) is presented. Several quantitative structure-activity relationship (QSAR) models based on molecular topology have been developed to predict inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha ([Formula: see text]) mediated anti-ulcerative colitis (UC) activity and protective activity against a dextran sulfate sodium (DSS)-induced UC model. Each one has been used for the screening of four previously selected compounds as potential therapeutic agents for UC: alizarin-3-methyliminodiacetic acid (AMA), Calcein, (+)-dibenzyl-L-tartrate, and Ro 41-0960.

Latest advances in molecular topology applications for drug discovery.

Introduction: Molecular topology (MT) has emerged in recent years as a powerful approach for the in silico generation of new drugs. In the last decade, its application has become more and more popular among the leading research groups in the field of quantitative structure-activity relationships (QSAR) and drug design. This has, in turn, contributed to the rapid development of new techniques and applications of MT in QSAR studies, as well as the introduction of new topological indices.

Novel cancer chemotherapy hits by molecular topology: dual Akt and Beta-catenin inhibitors.

Background And Purpose: Colorectal and prostate cancers are two of the most common types and cause of a high rate of deaths worldwide. Therefore, any strategy to stop or at least slacken the development and progression of malignant cells is an important therapeutic choice. The aim of the present work is the identification of novel cancer chemotherapy agents.

Predicting antiprotozoal activity of benzyl phenyl ether diamine derivatives through QSAR multi-target and molecular topology.

Multi-target QSAR is a novel approach that can predict simultaneously the activity of a given chemical compound on different pharmacological targets. In this work, we have used molecular topology and statistical tools such as multilinear regression analysis and artificial neural networks, to achieve a multi-target QSAR model capable to predict the antiprotozoal activity of a group of benzyl phenyl ether diamine derivatives. The activity was related to three parasites with a high prevalence rate in humans: Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmania donovani.

Molecular topology applied to the discovery of 1-benzyl-2-(3-fluorophenyl)-4-hydroxy-3-(3-phenylpropanoyl)-2H-pyrrole-5-one as a non-ligand-binding-pocket antiandrogen.

We report the discovery of 1-benzyl-2-(3-fluorophenyl)-4-hydroxy-3-(3-phenylpropanoyl)-2H-pyrrole-5-one as a novel non-ligand binding pocket (non-LBP) antagonist of the androgen receptor (AR) through the application of molecular topology techniques. This compound, validated through time-resolved fluorescence resonance energy transfer and fluorescence polarization biological assays, provides the basis for lead optimization and structure-activity relationship analysis of a new series of non-LBP AR antagonists. Induced-fit docking and molecular dynamics studies have been performed to establish a consistent hypothesis for the interaction of the new active molecule on the AR surface.

The prediction of human intestinal absorption based on the molecular structure.

Human Intestinal Absorption (HIA) has been modeled many times by using classification models. However, regression models are scarce. Here, Artificial Neural Networks (ANNs) are implemented for this purpose.

QSAR multi-target in drug discovery: a review.

The main purpose of the present review is to summarize the most significant works up to date in the field of multi-target QSAR (mt-QSAR), in order to emphasize the importance that this technique has acquired over the last decade. Unlike traditional QSAR techniques, mt-QSAR permits to calculate the probability of activity of a given compound against different biological or pharmacological targets. In simple terms, a single equation for multiple outputs.

Molecular topology - dissimilar similarities.

The present paper depicts the role of molecular topology in the study of similarity-dissimilarity between molecular structures. It proves that molecular topology represents a very useful tool for getting common patterns of pharmacological activity and hence an efficient approach for the search of novel lead drugs.

Novel potential agents for ulcerative colitis by molecular topology: suppression of IL-6 production in Caco-2 and RAW 264.7 cell lines.

Ulcerative colitis (UC) is an immune-mediated chronic and relapsing intestinal inflammatory disease. Interleukin (IL)-6, a pro-inflammatory cytokine, plays a key role in the uncontrolled intestinal inflammatory process, which is a main characteristic of UC. In this work, a quantitative structure-activity relationship model based on molecular topology (MT) has been built up to predict the IL-6 mediated anti-UC activity.