Evaluating efflux pump inhibition in Staphylococcus aureus 1199B strain using thiadiazine-derived compounds: In vitro and in silico approaches.

Thiadiazines are heterocyclic compounds known for some pharmacological activities. However, the ability of these compounds and their derivatives to act as antibacterial agents and inhibitors of the efflux system in resistant bacteria remains unknown. This study aims to evaluate the antibacterial and NorA efflux pump inhibitory activities of thiadiazine-derived compounds (IJ14, IJ15, IJ16, IJ17, IJ18, IJ19, and IJ20) against the Staphylococcus aureus 1199B strain.

Nanomolar activity of coumarin-3-thiosemicarbazones targeting Trypanosoma cruzi cruzain and the T. brucei cathepsin L-like protease.

Trypanosoma cruzi (T. cruzi) and Trypanosoma brucei (T. brucei) urgently demand innovative drug development due to their impact on public health worldwide.

Anticancer Drug Discovery from Natural Compounds Targeting PI3K/AKT/mTOR Signaling Pathway.

The term cancer is used to describe a complex pathology characterized by the uncontrollable proliferation of cells, which displays a fast metastatic spread, being a disease with difficult treatment. In this context, Phosphatidylinositol 3-kinase (PI3K) represents a promising pathway to be inhibited, aiming to develop anticancer agents, since it performs a pivotal role in regulating essential cellular processes, including cell proliferation, growth, autophagy, and apoptosis. In parallel, natural compounds can effectively represent a therapeutic strategy to fight against malignant cells.

The Multitarget Action of Vitamins in the Ischemic Stroke.

A stroke, also known as a cerebral hemorrhage, occurs when there is an interruption in the blood supply to a part of the brain, resulting in damage to brain cells. This issue is one of the leading causes of death in developed countries, currently killing about 5 million people annually. Individuals who survive ischemic stroke often face serious vision problems, paralysis, dementia, and other sequelae.

Assessment In vitro and In silico of the Activity of Thiadiazines as NorA Efflux Pump Inhibitors.

Antimicrobials fight microorganisms, preventing and treating infectious diseases. However, antimicrobial resistance (AMR) is a growing concern due to the inappropriate and excessive use of these drugs. Several mechanisms can lead to resistance, including efflux pumps such as the NorA pump in Staphylococcus aureus, which reduces the effectiveness of fluoroquinolones.

Recent advances in the molecular design and applications of viral RNA-targeting antiviral modalities.

Pathogenic viruses are a profound threat to global public health, underscoring the urgent need for the development of efficacious antiviral therapeutics. The advent of RNA-targeting antiviral strategies has marked a significant paradigm shift in the management of viral infections, offering a potent means of control and potential cure. In this review, we delve into the cutting-edge progress in RNA-targeting antiviral agents, encompassing antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), small and bifunctional molecules.

Oropouche virus - The "Newest" invisible public enemy?

This perspective underscores the rising challenge posed by emerging diseases against the backdrop of modern advancements in global public health understanding. It particularly highlights the emergence of the Oropouche virus (OROV) as a significant global threat, detailing its transmission dynamics, symptoms, and epidemiological impact, with a focus on its historical and current manifestations. It further delves into the molecular aspects of OROV, elucidating its unique characteristics, lack of structural similarity with other arboviruses, and the limited progress in medicinal chemistry research.

A consensus reverse docking approach for identification of a competitive inhibitor of acetyltransferase enhanced intracellular survival protein from Mycobacterium tuberculosis.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), which remains a significant global health challenge. The emergence of multidrug-resistant (MDR) Mtb strains imposes the development of new therapeutic strategies. This study focuses on the identification and evaluation of potential inhibitors against Mtb H37Ra through a comprehensive screening of an in-house chemolibrary.

Insights on Natural Products Against Amyotrophic Lateral Sclerosis (ALS).

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that causes the death of motor neurons and consequent muscle paralysis. Despite many efforts to address it, current therapy targeting ALS remains limited, increasing the interest in complementary therapies. Over the years, several herbal preparations and medicinal plants have been studied to prevent and treat this disease, which has received remarkable attention due to their blood-brain barrier penetration properties and low toxicity.

Cyrene™ as a tyrosinase inhibitor and anti-browning agent.

The tyrosinase pathway takes part in the enzymatic process of food browning and is primarily responsible for food spoilage - manifesting itself from a decrease in its nutritional value to a deterioration of taste, which consequently leads to a gradual loss of shelf life. Finding safe and bio-based tyrosinase inhibitors and anti-browning agents may be of great importance in agriculture and food industries. Herein, we showed that Cyrene™ exhibits tyrosinase inhibitory activity (IC: 268.

Emerging drug design strategies in anti-influenza drug discovery.

Influenza is an acute respiratory infection caused by influenza viruses (IFV), According to the World Health Organization (WHO), seasonal IFV epidemics result in approximately 3-5 million cases of severe illness, leading to about half a million deaths worldwide, along with severe economic losses and social burdens. Unfortunately, frequent mutations in IFV lead to a certain lag in vaccine development as well as resistance to existing antiviral drugs. Therefore, it is of great importance to develop anti-IFV drugs with high efficiency against wild-type and resistant strains, needed in the fight against current and future outbreaks caused by different IFV strains.

Natural Compounds as Inhibitors of Aβ Peptide and Tau Aggregation.

Neurodegenerative conditions like Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) encompass disorders characterized by the degeneration of neurons in specific circumstances. The quest for novel agents to influence these diseases, particularly AD, has unearthed various natural compounds displaying multifaceted activities and diverse pharmacological mechanisms. Given the ongoing extensive study of pathways associated with the accumulation of neurofibrillary aggregates and amyloid plaques, this paper aims to comprehensively review around 130 studies exploring natural products.

Development of chalcone-like derivatives and their biological and mechanistic investigations as novel influenza nuclear export inhibitors.

Concerning the emergence of resistance to current anti-influenza drugs, our previous phenotypic-based screening study identified the compound A9 as a promising lead compound. This chalcone analog, containing a 2,6-dimethoxyphenyl moiety, exhibited significant inhibitory activity against oseltamivir-resistant strains (H1N1 pdm09), with an EC value of 1.34 μM.

"You've got the Body I've got the Brains" - Could the current AI-based tools replace the human ingenuity for designing new drug candidates?

The emergence of artificial intelligence (AI) tools has transformed the landscape of drug discovery, providing unprecedented speed, efficiency, and cost-effectiveness in the search for new therapeutics. From target identification to drug formulation and delivery, AI-driven algorithms have revolutionized various aspects of medicinal chemistry, significantly accelerating the drug design process. Despite the transformative power of AI, this perspective article emphasizes the limitations of AI tools in drug discovery, requiring inventive skills of medicinal chemists.

Naphthoquinone Derivatives Targeting Melanoma.

Cancer is responsible for high mortality rates worldwide, representing a serious health problem. In this sense, melanoma corresponds to the most aggressive type of skin cancer, being the cause of the highest death rates. Therapeutic strategies for the treatment of melanoma remain limited, with problems associated with toxicity, serious side effects, and mechanisms of resistance.

PI3K Signaling Pathways as a Molecular Target for Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most common type of cancer that affects the central nervous system (CNS). It currently accounts for about 2% of diagnosed malignant tumors worldwide, with 296,000 new cases reported per year. The first-choice treatment consists of surgical resection, radiotherapy, and adjuvant chemotherapy, which increases patients' survival by 15 months.

Potentiating-antibiotic activity and absorption, distribution, metabolism, excretion and toxicity properties (ADMET) analysis of synthetic thiadiazines against multi-drug resistant (MDR) strains.

Background: Thiadiazines are heterocyclic compounds that contain two nitrogen atoms and one sulfur atom in their structure. These synthetic molecules have several relevant pharmacological activities, such as antifungal, antibacterial, and antiparasitic.

Objectives: The present study aimed to evaluate the possible in vitro and in silico interactions of compounds derived from thiadiazines.

Inhibitors Targeting Hepatitis C Virus (HCV) Entry.

Infections caused by the Hepatitis C virus (HCV) affect around 70 million people worldwide, leading to serious liver problems, such as fibrosis, steatosis, and cirrhosis, in addition to progressing to hepatocellular carcinoma and becoming globally the main cause of liver disease. Despite great therapeutic advances in obtaining pan-genotypic direct-acting antivirals (DAAs), around 5-10% of affected individuals are unable to eliminate the virus by their own immune system's activity. Still, there are no licensed vaccines so far.

Design, synthesis, antiviral evaluation, and In silico studies of acrylamides targeting nsP2 from Chikungunya virus.

The Togaviridae family comprises several New- and Old-World Alphaviruses that have been responsible for thousands of human illnesses, including the RNA arbovirus Chikungunya virus (CHIKV). Firstly, it was reported in Tanzania in 1952 but rapidly it spread to several countries from Europe, Asia, and the Americas. Since then, CHIKV has been circulating in diverse countries around the world, leading to increased morbidity rates.

BACE-1 Inhibitors Targeting Alzheimer's Disease.

The accumulation of amyloid-β (Aβ) is the main event related to Alzheimer's disease (AD) progression. Over the years, several disease-modulating approaches have been reported, but without clinical success. The amyloid cascade hypothesis evolved and proposed essential targets such as tau protein aggregation and modulation of β-secretase (β-site amyloid precursor protein cleaving enzyme 1 - BACE-1) and γ-secretase proteases.

Preclinical data on morpholine (3,5-di-tertbutyl-4-hydroxyphenyl) methanone induced anxiolysis.

Trimetozine is used to be indicated for the treatment of mental illnesses, particularly anxiety. The present study provides data on the pharmacological profile of trimetozine derivative morpholine (3,5-di-tert-butyl-4-hydroxyphenyl) methanone (LQFM289) which was designed from molecular hybridization of trimetozine lead compound and 2,6-di-tert-butyl-hydroxytoluene to develop new anxiolytic drugs. Here, we conduct molecular dynamics simulations, docking studies, receptor binding assays, and in silico ADMET profiling of LQFM289 before its behavioral and biochemical assessment in mice within the dose range of 5-20 mg/kg.

Natural Coumarin Derivatives Targeting Melanoma.

In general, a cancerous process starts from uncontrolled cell growth, apoptosis, and rapid proliferation of cellular clones, as well as, reactive oxygen species (ROS) and imbalance of ROS-antioxidant production also could be involved in the genesis of the disease. Cancer has accounted for millions of deaths worldwide every year, representing a relevant threat to human lives. In this context, malignant melanoma represents the most aggressive and deadliest type of cancer, leading to increased rates of patient deaths.