Phylum Cnidaria has been an excellent source of natural products, with thousands of metabolites identified. Many of these have not been screened in bioassays. The aim of this study was to explore the potential of 5600 Cnidaria natural products (after...
The chemical structure of a drug determines its physicochemical properties, further determines its ADME/Tox properties, and ultimately affects its pharmacological activity. Medicinal chemists can regulate the pharmacological activity of drug molecule...
Acylhydrazones are still an important framework to the design of new bioactive compounds. As treatment of chronic pain represents a clinical challenge, we decided to modify the structure of LASSBio-1514 (1), previously described as anti-inflammatory...
This review covers the construction of drug-like 2H-benzopyrans and related libraries using solid-phase parallel synthesis. In this context, the preparation of substituted benzopyrans such as mono-, di- and trisubstituted benzopyran derivatives and a...
The purpose of the present study was to experimentally confirm the thermodynamic correlation between the intrinsic liquid–liquid phase separation (LLPS) concentration (
We propose a computational workflow to design novel drug-like molecules by combining the global optimization of molecular properties and protein-ligand docking with machine learning. However, most existing methods depend heavily on experimental data,...
We have achieved site-specific conjugation of several haloacetamide derivatives into designated cysteines on bacteriophage T7-displayed peptides, which are fused to T7 capsid protein gp10. This easiest gp10 based-thioetherification (10BASEd-T) underg...
Terpenoids constitute one of the most widespread phytoconstituents, with complex chemical structures, a plurality of biological activities, and variable pharmacokinetic profiles. The emerging roles of terpenoids in drug design require an understandin...
Most pharmaceutical substances interact with several or even many molecular targets in the organism, determining the complex profiles of their biological activity. Moreover, due to biotransformation in the human body, they form one or several metabol...
The drug development pipeline involves several stages including in vitro assays, in vivo assays, and clinical trials. For candidate selection, it is important to consider that a compound will successfully pass through these stages. Using graph neural...
Background: Flavonoids and phenolic acids are recognized for their diverse therapeutic potential, yet their translation into clinical applications remains limited by varying bioavailability and fragmented characterization across databases. A systemat...
A cheminformatics procedure for a partitioning model based on 135 natural compounds including Flavonoids, Saponins, Alkaloids, Terpenes and Triterpenes with drug-like features based on a descriptors pool was developed. The knowledge about the applica...
A series of 5-fluorouracil/coumarin and 5-fluorouracil/chromone hybrids were synthesized with good yields using click chemistry as the key step. The structures of these compounds and all intermediates were elucidated by spectroscopic analysis. Furthe...
Senkyunolide I (SI) is a natural phthalide that has drawn increasing interest for its potential as a cardio-cerebral vascular drug candidate. In this paper, the botanical sources, phytochemical characteristics, chemical and biological transformations...
Lipinski’s Rule of Five and Ghose filter are empirical guidelines for evaluating the drug-likeness of a compound, suggesting that orally active drugs typically fall within specific ranges for molecular descriptors such as hydrogen bond donors a...
Targeting cancer stem cells (CSCs) in anticancer discovery is very difficult due to the resistance of CSCs to conventional drugs, their low proliferation rate, improved DNA damage repair, and the overexpression of anti-apoptotic proteins and multidru...
Asthma is a chronic obstructive pulmonary disease, affecting approximately 300 million people worldwide. Current therapies have disadvantages such as side effects and high costs. Alternatively, herbal plants have been used for decades as focal medici...
Peptide therapeutics often fall outside classical small-molecule heuristics, such as Lipinski’s Rule of Five (Ro5), motivating the development of adapted filters and data-driven approaches to early drug-likeness assessment. We curated >300 k...
Molecular hybridization (MH) of heterocyclic rings has enabled scientists to design and develop novel drugs and drug-like candidates. In our previous work, considering the importance of MH, we synthesized different kinds of chloropyrazine-tethered py...
Diarrhea diseases caused by the intestinal protozoan parasite Giardia intestinalis are a major global health burden. Moreover, there is an ongoing need for novel anti-Giardia drugs due to drawbacks with currently available treatments. This paper repo...
The p53 protein is one of the most important tumor suppressors that are frequently inactivated in cancer cells. This inactivation occurs either because the TP53 gene is mutated or deleted, or due to the p53 protein inhibition by endogenous negative r...
Tauopathies, including Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and frontotemporal lobar degeneration with tau pathology, are unified by pathogenic tau misfolding, post-translational modif...
Background/Objectives: Early-stage antibacterial discovery requires balancing activity with broader developability-related properties. This study developed a Fivefold Maximum Drug-Likeness strategy (5F-MDL) as a multidimensional, developability-aware...
A highly stereo-selective, one-pot, multicomponent method was chosen to synthesize the novel functionalized 1, 3-cycloaddition spirooxindoles (SOXs) (4a–4h). Synthesized SOXs were analyzed for their drug-likeness and ADME parameters and screene...
Along with the increasing resistance of Candida spp. to some antibiotics, it is necessary to find new antifungal drugs, one of which is from the medicinal plant Red Betel (Piper crocatum). The purpose of this research is to isolate antifungal constit...
The innate immunity toll-like receptor 4 (TLR4) system is a receptor of paramount importance as a therapeutic target. Virtual screening following a “computer-aided drug repurposing” approach was applied to the discovery of novel TLR4 modu...
The quantitative structure–activity relationship (QSAR) methodology was used to predict the blood–brain permeability (log BB) for 65 synthetic heterocyclic compounds tested as promising drug candidates. The compounds were characterized by...
A series of 5-FU-ASA hybrids were synthesized with good yields using click chemistry as the key step. The structures of these compounds were elucidated by spectroscopic analysis. Finally, an optimal pharmacokinetic profile was also estimated for each...
The physicochemical properties of classical lignans, neolignans, flavonolignans and carbohydrate-lignan conjugates (CLCs) were analysed to assess their ADMET profiles and establish if these compounds are lead-like/drug-like and thus have potential to...
The success of antibody therapeutics is strongly influenced by their multifunctional nature that couples antigen recognition mediated by their variable regions with effector functions and half-life extension mediated by a subset of their constant reg...
Chinese herbal medicine has recently gained worldwide attention. The curative mechanism of Chinese herbal medicine is compared with that of western medicine at the molecular level. The treatment mechanism of most Chinese herbal medicines is still not...
Cyclin D1 (CCND1) and cyclin-dependent kinase 4 (CDK4) both play significant roles in regulating cell cycle progression, while polo-like kinase 1 (PLK1) regulates cell differentiation and tumor progression, and activates cancer stem cells (CSCs), wit...
Pyrrolizidine alkaloids (PAs) are heterocyclic organic compounds of natural origin synthesized by either plants or microorganisms [...]
Background: The leading cause of cancer-related deaths globally is lung cancer, and the P2X7 receptor (P2X7R) is a promising therapeutic target due to its role in the disease progression. Methods: A deep learning-based molecular generation framework...
Despite the achievements of antiretroviral therapy, discovery of new anti-HIV medicines remains an essential task because the existing drugs do not provide a complete cure for the infected patients, exhibit severe adverse effects, and lead to the app...
The present work is devoted to the synthesis of imidazo[2,1-b][1,3]thiazine derivatives as possible anti-inflammatory agents. The synthetic approach to (2-pyridinyloxy) substituted imidazo[2,1-b][1,3]thiazines based on the interaction of the polysubs...
The discovery of novel therapeutic compounds through de novo drug design represents a critical challenge in the field of pharmaceutical research. Traditional drug discovery approaches are often resource intensive and time consuming, leading researche...
As an appealing approach for discovering novel leads, the key advantage of de novo drug design lies in its ability to explore a much broader dimension of chemical space, without being confined to the knowledge of existing compounds. So far, many gene...
G protein-coupled receptors (GPCRs) are a superfamily of proteins classically described as monomeric transmembrane (TM) receptors. However, increasing evidence indicates that many GPCRs form higher-order assemblies made up of monomers pertaining to i...
A series of fourteen new asymmetrical 1,3-diketone derivatives have been synthesized and evaluated in the ABTS, FRAP and DPPH assays as a new chemotype with antioxidant and drug-like properties. All the compounds displayed low cytotoxicity in compari...
Several natural products (NPs) have displayed varying in vitro activities against methicillin-resistant Staphylococcus aureus (MRSA). However, few of these compounds have not been developed into potential antimicrobial drug candidates. This may be du...
Specific drugs are well known to have the capacity to induce Parkinson-like symptoms. Parkinson-like events are side effects that may persist for an extended period even after drug administration is discontinued. Although these events can be triggere...
Marine trypanocidal natural products are, most often, reported with trypanocidal activity and selectivity against human cell lines. The triaging of hits requires a consideration of chemical tractability for drug development. We utilized a combined Li...
Background: Pancreatitis, encompassing acute (AP), severe acute (SAP), and chronic (CP) forms, is a life-threatening inflammatory disorder with limited therapeutic options. Current management is largely supportive, highlighting the urgent need for no...
Monoterpenoids are a structurally diverse class of natural products with a long-standing history of therapeutic use. Despite their promising bioactivities, their clinical development has been limited by dose-dependent toxicities, poor pharmacokinetic...
A small library of new drug-1,3,4-thiazidazole hybrid compounds (3a–3i) was synthesized, characterized, and assessed for their acetyl cholinesterase enzyme (AChE) inhibitory and free radical scavenging activities. The newly synthesized derivati...
Prunus mahaleb L., also known as white mahaleb, and native to the Kurdistan region of Iraq, has significant nutraceutical and therapeutic ingredients. The seeds are rich in conjugated fatty acids with small quantities of cyanogenic glycosides, coumar...
Background: Geraniol is an acyclic monoterpene widely distributed in the essential oils of aromatic species such as Cymbopogon citratus, Pelargonium graveolens, and Rosa damascena, It is known for its antioxidant, anti-inflammatory, neuroprotective,...
With the ambition to identify novel chemical starting points that can be further optimized into small drug-like inhibitors of insulin-regulated aminopeptidase (IRAP) and serve as potential future cognitive enhancers in the clinic, we conducted an ult...
In the present work, the synthesis of new ethacrynic acid (EA) derivatives containing nitrogen heterocyclic, urea, or thiourea moieties via efficient and practical synthetic procedures was reported. The synthesised compounds were screened for their a...
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