Alejandro Speck Planche

University of Porto | UP · LAQV@REQUIMTE/Department of Chemistry and Biochemistry

Introduction: Drug discovery has provided modern societies with the means to fight against many diseases. In this sense, computational methods have been at the forefront, playing an important role in rationalizing the search for novel drugs. Yet, tackling phenomena such as the multi-genic nature of diseases and drug resistance are limitations of t...

Peptide discovery is a very active research area. Computational methods have become an essential part of the process of designing peptides with desired properties. However, such methods have several drawbacks such as the prediction of unspecific biological effects (generally activity or hemotoxicity), the consideration of only one type of endpoint,...

Respiratory viruses are infectious agents, which can cause pandemics. Although nowadays the danger associated with respiratory viruses continues to be evidenced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as the virus responsible for the current COVID-19 pandemic, other viruses such as SARS-CoV-1, the influenza A and B virus...

Pancreatic cancer (PANC) is a dangerous type of cancer that is a major cause of mortality worldwide and exhibits a remarkably poor prognosis. To date, discovering anti-PANC agents remains a very complex and expensive process. Computational approaches can accelerate the search for anti-PANC agents. We report for the first time two models that combin...

Inflammation involves a complex biological response of the body tissues to damaging stimuli. When dysregulated, inflammation led by biomolecular mediators such as caspase-1 and tumor necrosis factor-alpha (TNF-alpha) can play a detrimental role in the progression of different medical conditions such as cancer, neurological disorders, autoimmune dis...

Hypertension is a medical condition that affects millions of people worldwide. Despite the high efficacy of the current antihypertensive drugs, they are associated with serious side effects. Peptides constitute attractive options for chemical therapy against hypertension, and computational models can accelerate the design of antihypertensive peptid...

Respiratory viruses continue to afflict mankind. Among them, pathogens such as coronaviruses [including the current pandemic agent known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] and the one causing influenza A (IAV) are highly contagious and deadly. These can evade the immune system defenses while causing a hyperinflammatory...

Tuberculosis remains the most afflicting infectious disease known by humankind, with one quarter of the population estimated to have it in the latent state. Discovering antituberculosis drugs is a challenging, complex, expensive, and time-consuming task. To overcome the substantial costs and accelerate drug discovery and development, drug repurposi...

Parasitic diseases remain as unresolved health issues worldwide. While for some parasites the treatments involve drug combinations with serious side effects, for others, chemical therapies are inefficient due to the emergence of drug resistance. This urges the search for novel antiparasitic agents able to act through multiple mechanisms of action....

Background Cyclin-dependent kinase 4 (CDK4) and the human epidermal growth factor receptor 2 (HER2) are two of the most promising targets in oncology research. Thus, a series of computational approaches have been applied to the search for more potent inhibitors of these cancer-related proteins. However, current approaches have focused on chemical a...

Artificial Intelligence revolutionizes the drug development process that can quickly identify potential biologically active compounds from millions of candidate within a short span of time. The present review is an overview based on some applications of Machine Learning based tools such as GOLD, DeepPVP, LIBSVM, etc and the algorithms involved such...

Liver cancers are one of the leading fatal diseases among malignant neoplasms. Current chemotherapeutic treatments used to fight these illnesses have become less efficient in terms of both efficacy and safety. Therefore, there is a great need of search for new anti-liver cancer agents and this can be accelerated by using computer-aided drug discove...

Progress in the application of machine learning (ML) to the physical and life sciences has been rapid. A decade ago, the method was mainly of interest to those in computer science departments, but more recently ML tools have been developed that show significant potential across wide areas of science. There is a growing consensus that ML software, a...

Background Alzheimer’s disease is characterized by a progressive pattern of cognitive and functional impairment, which ultimately leads to death. Computational approaches have played an important role in the context of drug discovery for anti-Alzheimer therapies. However, most of the computational models reported to date have been focused on only o...

Background Fragment-based drug design (FBDD) has established itself as a promising approach in modern drug discovery, accelerating and improving lead optimization, while playing a crucial role in diminishing the high attrition rates at all stages in the drug development process. On the other hand, FBDD has benefited from the application of computat...

Pesticides are chemical or biological agents, whose ultimate purpose is to eradicate pests, thus preventing crop losses by protecting the plants from multiple diseases. Despite the importance of their use, pesticides constitute a focus of serious concern because of their harmful effects on the environment. In silico approaches have played a key rol...

Background: Staphylococcus aureus is a gram-positive spherical bacterium commonly present in nasal fossae and in the skin of healthy people; however, in high quantities, it can lead to complications that compromise health. The pathologies involved include simple infections, such as folliculitis, acne, and delay in the process of wound healing, as...

This work discusses the idea that drug discovery, instead of being performed through a series of filtering-based stages, should be viewed as a multi-scale optimization problem. Here, the most promising multi-scale models are analyzed in terms of their applications, advantages, and limitations in the search for more potent and safer chemicals agains...

Epigenetics has become a focus of interest in drug discovery. In this sense, bromodomain-containing proteins have emerged as potential epigenetic targets in cancer research and other therapeutic areas. Several computational approaches have been applied to the prediction of bromodomain inhibitors. Nevertheless, such approaches have several drawbacks...

Pancreatic cancers are widely recognized as a group of neoplasms with one of the poorest prognoses in oncology research. Despite the advances achieved in drug design and development, there is no effective cure for pancreatic cancers, and the current chemotherapeutic regimens increase the survival rate by only a few months. As an integral part of al...

Machine learning methods have revolutionized modern science, providing fast and accurate solutions to multiple problems. However, they are commonly treated as "black boxes". Therefore, in important scientific fields such as medicinal chemistry and drug discovery, machine learning methods are restricted almost exclusively to the task of performing p...

In this work, we introduce the first multitasking model for quantitative structure-biological effect relationships focused on the simultaneous exploration of antibacterial activity against Gram-negative pathogens and in vitro safety profiles related to absorption, distribution, metabolism, elimination, and toxicity (ADMET). The multitasking model f...

Nanoparticles (NPs) are part of our daily life, having a wide range of applications in engineering, physics, chemistry, and biomedicine. However, there are serious concerns regarding the harmful effects that NPs can cause to the different biological systems and their ecosystems. Toxicity testing is an essential step for assessing the potential risk...

Breast cancer is the most frequent cancer reported in women, being responsible for hundreds of thousands of deaths. Chemotherapy has proven to be effective against this malignant neoplasm depending on different biological factors such as the histopathology, grade, and stage, among others. However, breast cancer cells have become resistant to curren...

Hepatitis C constitutes an unresolved global health problem. This infectious disease is caused by the hepatotropic hepatitis C virus (HCV), and it can lead to the occurrence of life-threatening medical conditions such as cirrhosis and liver cancer. Nowadays, major clinical concerns have arisen due to the appearance of multidrug resistance (MDR), an...

Drug discovery is an expensive, time-consuming process and the modern drug discovery community is constantly challenged not only with discovering novel bioactive agents to combat resistance from known diseases and fight against new ones, but to do so in a way that is economically effective. Advances in both experimental and theoretical/computationa...

In this chapter, we propose a novel computational methodology for the virtual design and screening of peptides with potential anticancer activity against different cancer cell lines, and low cytotoxicity against diverse healthy mammalian cells. In this context, a multitasking (mtk) chemoinformatic model combining Broto–Moreau autocorrelations with...

Human immunodeficiency virus (HIV) is responsible for causing the life-threatening condition known as acquired immune deficiency syndrome (AIDS). Current antiretroviral regimens are usually effective in halting the progression of HIV/AIDS, but serious concerns exist regarding the emergence of multidrug resistance and the prevalence of side effects....

The last decade has been seeing an increase of public-private partnerships in drug discovery, mostly driven by factors such as the decline in productivity, the high costs, time, and resources needed, along with the requirements of regulatory agencies. In this context, traditional computer-aided drug discovery techniques have been playing an importa...

Nanotechnology is a newly emerging field, posing substantial impacts on society, economy, and the environment. In recent years, the development of nanotechnology has led to the design and large-scale production of many new materials and devices with a vast range of applications. However, along with the benefits, the use of nanomaterials raises many...

Nanotechnology is a newly emerging field, posing substantial impacts on society, economy, and theenvironment. In recent years, the development of nanotechnology has led to the design and large-scaleproduction of many new materials and devices with a vast range of applications. However, along withthe benefits, the use of nanomaterials raises many qu...

Antimicrobial peptides (AMPs) represent promising alternatives to fight against bacterial pathogens. However, cellular toxicity remains one of the main concerns in the early development of peptide-based drugs. This work introduces the first multitasking (mtk) computational model focused on performing simultaneous prediction of antibacterial activit...

Fullerenes are carbon allotropes, and they have called the attention of scientists in the last 15 years. In nanotechnology, fullerenes have had several promising applications in medicinal chemistry, pharmaceutical sciences, biomedicine, and related disciplines. Particularly, the design and biological evaluation of fullerene-C-60 derivatives as anti...

Chagas' disease, which occurs particularly in South America is a human tropical parasitic disease, caused by Trypanosoma cruzi. A virtual screening in an in-house databank (SISTEMATX), of 469 Apocynaceae indole alkaloids, using models developed with fragment descriptors using Support Vector Machines (SVM) and Decision Trees (DT) were performed. A d...

Bacteria have been one of the world's most dangerous and deadliest pathogens for mankind, nowadays giving rise to significant public health concerns. Given the prevalence of these microbial pathogens and their increasing resistance to existing antibiotics, there is a pressing need for new antibacterial drugs. However, development of a successful dr...

Enterococci are Gram-positive bacteria responsible for causing multiple nosocomial infections in humans. Chemoinformatics could be a great ally of medicinal chemistry in the search for efficacious anti-enterococci drugs. Current methods cannot model the anti-enterococci activity and ADMET (absorption, distribution, metabolism, elimination, toxicity...

Drug discovery is aimed at finding therapeutic agents for the treatment of many diverse diseases and infections. However, this is a very slow an expensive process, and for this reason, in silico approaches are needed to rationalize the search for new molecular entities with desired biological profiles. Models focused on quantitative structure-activ...

Neglected diseases are infections that thrive mainly among underdeveloped countries, particularly those belonging to regions found in Asia, Africa, and America. One of the most complex diseases is noma, a dangerous health condition characterized by a polymicrobial and opportunistic nature. The search for potent and safer antibacterial agents agains...

Resistance of bacteria to current antibiotics is an alarming health problem. In this sense, Pseudomonas represents a genus of Gram-negative pathogens which has emerged as one of the most dangerous species causing nosocomial infections. Despite the effort of the scientific community, drug resistant strains of bacteria belonging to Pseudomonas spp. p...

The assessment of acute toxicity is one of the most important stages to ensure the safety of chemicals with potential applications in pharmaceutical sciences, biomedical research, or any other industrial branch. A huge and indiscriminate number of toxicity assays have been carried out on laboratory animals. Computational approaches involving models...

Introduction: Drug discovery is the process of designing new candidate medications for the treatment of diseases. Over many years, drugs have been identified serendipitously. Nowadays, chemoinformatics has emerged as a great ally, helping to rationalize drug discovery. In this sense, quantitative structure-activity relationships (QSAR) models have...

We introduce the first quantitative structure-activity relationship (QSAR) perturbation model for probing multiple antibacterial profiles of nanoparticles (NPs) under diverse experimental conditions. The dataset is based on 300 nanoparticles containing dissimilar chemical compositions, sizes, shapes and surface coatings. In general terms, the NPs w...

Nanotechnology is a newly emerging field, posing substantial impacts on society, economy, and the environment. In recent years, the development of nanotechnology has led to the design and large-scale production of many new materials and devices with a vast range of applications. However, along with the benefits, the use of nanomaterials raises many...

Gram-positive cocci are increasingly antibiotic-resistant bacteria responsible for causing serious diseases. Chemoinformatics can help to rationalize the discovery of more potent and safer antibacterial drugs. We have developed a chemoinformatic model for simultaneous prediction of anti-cocci activities, and profiles involving absorption, distribut...

Nanomaterials have revolutionized modern science and technology due to their multiple applications in engineering, physics, chemistry, and biomedicine. Nevertheless, the use and manipulation of nanoparticles (NPs) can bring serious damages to living organisms and their ecosystems. For this reason, ecotoxicity and cytotoxicity assays are of special...

The study of quantitative structure-property relationships (QSPR) is important to study complex networks of chemical reactions in drug synthesis or metabolism or drug-target interactions networks. A difficult but also possible goal is the prediction of drug absorption, distribution, metabolism, and excretion (ADME) process with a single QSPR model....

The immune system helps to halt the infections caused by pathogenic microbial and parasitic agents. The ChEMBL database lists very large datasets of cytotoxicity of organic compounds but notably, a large number of compounds have unknown effects over molecular and cellular targets in the immune system. Flow Cytometry Analysis (FCA) is a very importa...

Nowadays, the interest in the search for new nanomaterials with improved electrical, optical, catalytic, and biological properties has been increased. Despite the potential benefits that can be gathered from the use nanoparticles, only a little attention has been paid to their possible toxic effects that may affect human health. In this context, se...

The study of the metabolism of xenobiotics by the human body is an essential stage in the complex and expensive process of drug discovery, being one of the main causes of disapproval and/or withdrawal of drugs. Regarding this, enzymes known as cytochromes P450 (CYPs) play a very decisive role in the biotransformation of many chemicals. For this rea...

Escherichia coli remains as one of the principal pathogens that cause nosocomial infections, being these, medical conditions which are increasingly common in healthcare facilities. Escherichia coli is intrinsically resistant to many antibiotics, and multidrug resistant (MDR) strains have emerged recently. Chemoinformatics has been a great ally of e...

Enterococci are dangerous opportunistic pathogens which are responsible of a huge number of nosocomial infections, displaying intrinsic resistance to many antibiotics. The battle against enterococci by using antimicrobial chemotherapies will depend on the design of new antibacterial agents with high activity and low toxicity. Multi-target methodolo...

Cancers can be considered as a group of diseases, where cells undergo an uncontrolled growth, and malignant tumors are formed. Between them, bladder cancer (BLC) is an aggressive type of cancer, which can propagate from the urinary bladder to other organs in the human body. BLC is the seventh most common cancer around the world, contributing with m...

Resistance of bacteria to current antibiotics has increased worldwide, being one of the leading unresolved situations in public health. Due to negligence regarding the treatment of community-acquired diseases, even healthcare facilities have been highly impacted by an emerging problem: nosocomial infections. Moreover, infectious diseases, including...

We develop a new QSPR-Perturbation theory model for Synthetic Pathways involving Assymetric Catalysis of Intra-molecular Carbolithiations. In doing so, we used calculated spectral moments of markov electron delocalization matrix for all molecules involved in the reactions. These descriptors and physical variables (temperature etc.) were used to cal...

Human immunodeficiency virus (HIV) is the responsible causal agent of acquired immunodeficiency syndrome (AIDS), a condition in humans where the immune system begins to fail, permitting the entry of diverse opportunistic infections. Until now, there is currently no available vaccine or cure for HIV or AIDS. Thus, the search for new anti-HIV therapi...

Leishmanioses is a human tropical parasitic disease that causes approximately 50,000 death cases annually. Secondary metabolites play an important role to propose new active lead structures, and studies highlights antiprotozoal activities of sesquiterpene lactones (SLs)¹. In view of this, we performed a virtual screening (VS) in an in-house databan...

Mycobacteria represent a group of pathogens which cause serious diseases in mammals, including the lethal tuberculosis (Mycobacterium tuberculosis). Despite the mortality of this community-acquired and nosocomial disease mentioned above, other mycobacteria may cause similar infections, acting as dangerous opportunistic pathogens. Additionally, resi...

Streptococci are a group of Gram-positive bacteria which are responsible for causing many diverse diseases in humans and other animals worldwide. The high prevalence of resistance of these bacteria to current antibacterial drugs is an alarming problem for the scientific community. The battle against streptococci by using antimicrobial chemotherapie...

Tuberculosis (TB) constitutes one of the most dangerous and serious health problems around the world. It is a very lethal disease caused by microorganisms of the genus mycobacterium, principally Mycobacterium tuberculosis (MTB) which affects humans. A very active field for the search of more efficient anti-TB chemotherapies is the use in silico met...

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The discovery of anti-cancer agents is an area which continues in accelerated expansion. Leukemias (Lkms) are among the most investigated cancers due to its high and dominant prevalence in children. Computer-aided drug design (CADD) methodologies have been extremely important for the discovery of potent anti-Lkms agents, providing essential insight...

The chemical risk assessment is determinant for the approval of any kind of chemical. Each aspect of chemical is taken into consideration for the new chemical legislation registration, evaluation, and authorization of chemicals (REACH). However, some improvements can be made in order to select and authorize a chemical. QSAR techniques have been use...

Bladder cancer (BLC) is a very dangerous and common disease which is characterized by an uncontrolled growth of the urinary bladder cells. In the field of chemotherapy, many compounds have been synthesized and evaluated as anti-BLC agents. The future design of more potent anti-BLC drugs depends on a rigorous and rational discovery, where the comput...

The search for new therapies against neurodegenerative disorders (NDs) such as Alzheimer (AD) and Parkinson (PD) constitutes a very active area. Although the scientific community has realized great efforts for the study of AD and PD from the most diverse points of view, these diseases remain incurable. Consequently, the design of new and more poten...

The discovery of new and more potent anti-cancer agents constitutes one of the most active fields of research in chemotherapy. Colorectal cancer (CRC) is one of the most studied cancers because of its high prevalence and number of deaths. In the current pharmaceutical design of more efficient anti-CRC drugs, the use of methodologies based on Chemoi...

Acquired immunodeficiency syndrome (AIDS) is a dangerous disease, which damages the immune system cells to the point that the immune system can no longer fight against other infections that it would usually be able to prevent. The causal agent is the human immunodeficiency virus (HIV), and for this reason, the search for more effective chemotherapi...