Cancers constitute a group of biological complex diseases, which are associated with great prevalence and mortality. These medical conditions are very difficult to tackle due to their multi-factorial nature, which includes their ability to evade the...
Multi-target drug discovery has become an essential strategy for treating complex diseases involving multiple molecular pathways. Traditional single-target approaches often fall short in addressing the multifactorial nature of conditions such as canc...
Multi-target drug design represents a paradigm shift in tackling the complexity and heterogeneity of diseases such as cancer. Conventional single-target therapies frequently face limitations due to network redundancy, pathway compensation, and adapti...
Polypharmacology is nowadays considered an increasingly crucial aspect in discovering new drugs as a number of original single-target drugs have been performing far behind expectations during the last ten years. In this scenario, multi-target drugs a...
Polypharmacology, the rational design of small molecules that act on multiple therapeutic targets, offers a transformative approach to overcome biological redundancy, network compensation, and drug resistance. This review outlines the scientific rati...
Epigenetics, referring to genetic modifications that change gene expression, but which are not encoded in DNA, has been shown to be related to oncology, with the potential to influence associated treatments. As such, epigenetic drugs comprise an impo...
In this continuing work, we have updated our recently proposed Multi-fingerprint Similarity Search algorithm (MuSSel) by enabling the generation of dominant ionized species at a physiological pH and the exploration of a larger data domain, which incl...
Multitarget drug discovery is one of the hottest topics and most active fields in the search for new molecules against Alzheimer’s disease (AD). Over the last 20 years, many promising multitarget-directed ligands (MTDLs) have been identified and deve...
Human immunodeficiency virus type-1 and hepatitis C virus (HIV/HCV) coinfection occurs when a patient is simultaneously infected with both human immunodeficiency virus type-1 (HIV-1) and hepatitis C virus (HCV), which is common today in certain popul...
Garlic (Allium sativum L.) has served as a food source and medicinal agent for over thousands of years. Bioactive constituents, including allicin, diallyl sulfide/disulfide/trisulfide, ajoene, and S-allyl-cysteine, demonstrate antioxidant, anti-infla...
Despite tremendous research efforts at every level, globally, there is still a lack of effective drugs for the treatment of Alzheimer′s disease (AD). The biochemical mechanisms of this devastating neurodegenerative disease are not yet clearly u...
Amongst the most prevalent malignancies worldwide, head and neck squamous cell carcinoma (HNSCC) is characterized by high morbidity and mortality. The failure of standard treatment modalities, such as surgery, radiotherapy, and chemotherapy, demands...
We describe the design, synthesis and structure–activity relationship of a novel series of 1-(4-(7-azaindole)-3,6-dihydropyridin-1-yl)alkyl-3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives with combined effects on the serotonin (5-HT1A) and d...
Inhibitors of epigenetic writers such as DNA methyltransferases (DNMTs) are attractive compounds for epigenetic drug and probe discovery. To advance epigenetic probes and drug discovery, chemical companies are developing focused libraries for epigene...
Metabolic Syndrome (MetS), a cluster of interconnected metabolic abnormalities, poses a growing global health burden. A well-established therapeutic target for the diseases is the incretin hormone glucagon-like peptide-1 (GLP-1); however, synthetic a...
Bis-(3-bromo-4-hydroxy)benzylidene cyclic compounds have been reported by us as epigenetic multiple ligands, but different substitutions at the two wings provided analogues with selective inhibition. Since the 1-benzyl-3,5-bis((E)-3-bromobenzylidene)...
The epidermal growth factor receptor (EGFR) is upregulated in glioblastoma, becoming an attractive therapeutic target. However, activation of compensatory pathways generates inputs to downstream PI3Kp110β signaling, leading to anti-EGFR therapeu...
Multifactorial diseases demand therapeutics that can modulate multiple targets for enhanced safety and efficacy, yet the clinical approval of multitarget drugs remains rare. The integration of machine learning (ML) and deep learning (DL) in drug disc...
Quantum dots (QDs) possess unique optical and electronic properties, enabling wide applications in biomedicine and optoelectronics, but their nanoscale size and surface chemistry could pose potential toxicity risks. This study established a systemati...
Drug–targeted therapies are promising approaches to treating tumors, and research on receptor–ligand interactions for discovering high-affinity targeted drugs has been accelerating drug development. This study presents a mechanism-driven...
The development and spread of Mycobacterium tuberculosis multi-drug resistant strains still represent a great global health threat, leading to an urgent need for novel anti-tuberculosis drugs. Indeed, in the last years, several efforts have been made...
Drug repurposing is a valuable tool for combating the slowing rates of novel therapeutic discovery. The Computational Analysis of Novel Drug Opportunities (CANDO) platform performs shotgun repurposing of 2030 indications/diseases using 3733 drugs/com...
This Special Issue, entitled “Molecules against Alzheimer”, gathers a number of original articles, short communications, and review articles on recent research efforts toward the development of novel drug candidates, diagnostic agents and therapeutic...
Pharmacogenomics is a rapidly growing field with the goal of providing personalized care to every patient. Previously, we developed the Computational Analysis of Novel Drug Opportunities (CANDO) platform for multiscale therapeutic discovery to screen...
The complex network of malfunctioning pathways occurring in the pathogenesis of neurodegenerative diseases (NDDs) represents a huge hurdle in the development of new effective drugs to be used in therapy. In this context, redox reactions act as crucia...
Ebola virus disease (EVD) is extremely virulent with an estimated mortality rate of up to 90%. However, the state-of-the-art treatment for EVD is limited to quarantine and supportive care. The 2014 Ebola epidemic in West Africa, the largest in histor...
Overproduction of reactive oxygen species (ROS) and alterations in metallostasis are common and related hallmarks in several neurodegenerative diseases (NDDs). Nature-based derivatives always represent an attractive tool in MTDL drug design, especial...
During tumor angiogenesis different growth factors, cytokines and other molecules interact closely with each other to facilitate tumor cell invasion and metastatic diffusion. The most intensively studied as molecular targets in anti-angiogenic therap...
HIV and HBV infection are both serious public health challenges. There are more than approximately 4 million patients coinfected with HIV and HBV worldwide, and approximately 5% to 15% of those infected with HIV are coinfected with HBV. Disease progr...
Predicting compounds with single- and multi-target activity and exploring origins of compound specificity and promiscuity is of high interest for chemical biology and drug discovery. We present a large-scale analysis of compound promiscuity including...
Parkinson’s disease (PD) is a complex neurodegenerative disorder lacking effective disease-modifying treatments. In this study, we integrated large-scale protein–protein interaction networks with a multi-modal graph neural network (GNN) t...
Among the various drug discovery methods, a very promising modern approach consists in designing multi-target-directed ligands (MTDLs) able to modulate multiple targets of interest, including the pathways where hydrogen sulfide (H2S) is involved. By...
Alzheimer’s disease (AD) is one of the most devastating neurodegenerative disorders, characterized by multiple pathological features. Therefore, multi-target drug discovery has been one of the most active fields searching for new effective anti-AD th...
Chemotherapy is commonly used for cancer treatment, however the lack of selectivity on healthy cells and the development of resistance phenomena are the major issues. A better understanding of cancer genetics helped the development of new targeted an...
Antibacterial drugs (commonly known as antibiotics) are essential for eradicating bacterial infections. Nowadays, antibacterial discovery has become an imperative need due to the lack of efficacious antibiotics, the ever-increasing development of mul...
Current oral medications for type 2 diabetes target a single main physiological mechanism. They either activate or inhibit receptors to enhance insulin sensitivity, increase insulin secretion, inhibit glucose absorption, or inhibit glucose production...
Around 70–85% of all breast cancer (BC) cases are estrogen receptor-positive (ER+). The third generation of aromatase inhibitors (AIs) is the first-line treatment option for these tumors. Despite their therapeutic success, they induce several s...
While selective inhibition is one of the key assets for a small molecule drug, many diseases can only be tackled by simultaneous inhibition of several proteins. An example where achieving selectivity is especially challenging are ligands targeting hu...
Marine drugs have long been used and exhibit unique advantages in clinical practices. Among the marine drugs that have been approved by the Food and Drug Administration (FDA), the protein–ligand interactions, such as cytarabine–DNA polyme...
Background/Objectives: Endocrine therapies that comprise anti-estrogens and aromatase inhibitors (AIs) are the standard treatment for estrogen receptor-positive (ER+) (Luminal A) breast cancer—the most prevalent subtype. However, the emergence...
Recent advances in precision oncology have led to significant breakthroughs through the targeting of defined oncogenic drivers. However, the clinical efficacy of single-target therapies is increasingly constrained by the intrinsic complexity and adap...
Childhood neuroblastoma (NB) is a malignant tumour that is a member of a class of embryonic tumours that have their origins in sympathoadrenal progenitor cells. There are five stages in the clinical NB staging system: 1, 2A, 2B, 3, 4S, and 4. For tho...
Brain network dysfunction in Alzheimer’s disease (AD) involves many proteins (enzymes), processes and pathways, which overlap and influence one another in AD pathogenesis. This complexity challenges the dominant paradigm in drug discovery or a single...
Histone deacetylases (HDACs) have become one of the main targets in cancer therapy due to their involvement in various biological processes, including gene regulation, cell proliferation, and differentiation. Microtubules, as key elements of the cell...
Despite extensive progress in understanding the pathology of Alzheimer’s disease (AD) over the last 50 years, clinical trials based on the amyloid–beta (Aβ) hypothesis have kept failing in late stage human trials. As a result, just f...
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by multiple factors, such as the progressive decline in the levels of the neurotransmitter acetylcholine, and the deregulation of the homeostasis of bio-metals, such as coppe...
The recent developments of fast reliable docking, virtual screening and other algorithms gave rise to discovery of many novel ligands of histamine receptors that could be used for treatment of allergic inflammatory disorders, central nervous system p...
Diabetes, a multifactorial metabolic disorder, demands the discovery of multi-targeting drugs with minimal side effects. This study investigated the multi-targeting antidiabetic potential of quercetin and kaempferol. The druggability and binding affi...
Amyloid β protein (Aβ) deposition has been implicated as the molecular driver of Alzheimer’s disease (AD) progression. The modulation of the formation of abnormal aggregates and their post-translational modification is strongly sugges...
Platinum (Pt) drugs have developed rapidly in clinical applications because of their broad and highly effective antitumor effects. In recent years, with the rapid development of immunotherapy, Pt-based antitumor agents have gained new challenges and...
of 6