Biological Activity Of Molecules Research Articles

ABIET: An explainable transformer for identifying functional groups in biological active molecules.

Recent advancements in deep learning have revolutionized the field of drug discovery, with Transformer-based models emerging as powerful tools for molecular design and property prediction. However, the lack of explainability in such models remains a significant challenge. In this study, we introduce ABIET (Attention-Based Importance Estimation Tool), an explainable Transformer model designed to identify the most critical regions for drug-target interactions - functional groups (FGs) - in biologically active molecules. Functional groups play a pivotal role in determining chemical behavior and biological interactions. Our approach leverages attention weights from Transformer-encoder architectures trained on SMILES representations to assess the relative importance of molecular subregions. By processing attention scores using a specific strategy - considering bidirectional interactions, layer-based extraction, and activation transformations - we effectively distinguish FGs from non-FG atoms. Experimental validation on diverse datasets targeting pharmacological receptors, including VEGFR2, AA2A, GSK3, JNK3, and DRD2, demonstrates the model's robustness and interpretability. Comparative analysis with state-of-the-art gradient-based and perturbation-based methods confirms ABIET's superior performance, with functional groups receiving statistically higher importance scores. This work enhances the transparency of Transformer predictions, providing critical insights for molecular design, structure-activity analysis, and targeted drug development.

Discrimination of chiral amino acid enantiomers through photoelectrochemical sensing platform

Chirality plays fundamental functions in the activity of biological molecules and broad classes of chemical reactions, but its recognition and detection still remain a great challenge. Herein, inspired by the stereo-control characteristics of chiral amino acids adjacent to the active sites of natural enzymes, a photoelectrochemical (PEC) chiral sensor was constructed by encapsulating Au nanoparticles with the recognition unit l-Cysteine into mesoporous BiVO4 skeleton. The chiral sensor exhibits a high sensitivity and selectivity discrimination of 3,4-dihydroxyphenylalanine (DOPA) enantiomers. The possible mechanism of enantioselectivity was proposed with the guidance of DFT calculations, suggesting that the origin of chiral selectivity lies in the different hydrogen bonds forms between l-Cys and DOPA. This work provides a powerful strategy for constructing PEC chiral sensing device with excellent chiral recognition performance.

Ferrocene functionalized oligomeric siloxane building blocks as potential linkers for biological active molecules

Despite the fact, that biologically active molecules (e.g., antioxidants, antibiotics and antiviral reagents) were investigated intensively in the last decades, new linker molecules and building blocks, which can enhance the activity and change the polarity of compounds is still a growing field in pharmaceutic research. The application of a ferrocene moiety in combination with a siloxane linker attached to a biological active molecule is realized in the present study for the first time. A method is introduced that uses mono- (FcLi) and dilithioferrocene (FcLi2) to perform anionic ring opening reactions of hexamethylcyclotrisiloxane (D3). The formation of lithium silanolate species αDnLi (α = Fc, D3 = (SiMe2O)3) was observed, followed by the termination of the ring opening reactions with chlorosilanes Cl–ω to obtain siloxane oligomers of type αDnω. Approaches were investigated to enable ω = SiMe2H and ω = SiMe2Cl functionality. It was shown, that oligomeric siloxanes were able to undergo further hydrosilylation reactions with the introduction of a phenol moiety.

Ionic Liquid Immobilized Pd Nanocatalysts for Chemoselective Reduction of Aliphatic/Aromatic Nitro Compounds

Abstract: In this work, we have successfully synthesized four types of ionic liquid-mediated Pd nanocatalysts and performed the physiochemical analysis of the developed Pd-based nanocatalysts using a transmission electron microscope (TEM), X-Ray diffraction analysis (XRD), X-ray photoelectron spectroscopy (XPS), and atomic absorption spectroscopy (AAS) analysis. The well-dispersed and fine Pd nanoparticles were recorded in the ILPdNPs-4 catalytic system. We used this catalytic system to reduce a series of aliphatic and aromatic compounds with nitro groups and developed various biologically active amine molecules. In the continuation of the same, we also reduced nitrolactone, which is considered one of the important starting materials for the synthesis of renin inhibitor aliskiren (Tekturna®, and worldwide as Rasilez®). We also completed the catalyst stability test and recycled the ILPdNPs-4 catalytic system for up to eight runs. No sign of metal leaching, Pd black formation, and agglomeration was recorded during recycling runs.

In silico study of solvation effects in solutions of biomolecules: possibilities of an approach based on the 3d-distribution of solvent atomic density

Biomolecular solvation plays one of the key roles in nature. The biological activity of molecules and the performance of their target functions depend on the features of this process. However, the study of the biomolecule hydration is a non-trivial task for both experimental methods and computer simulations. The paper demonstrates the possibilities of the non-empirical 3D-SDFT/3D-RISM approach based on the 3D-distribution of the solvent atomic density to study the features of biomolecule hydration using the example of a number of amino acids such as Gly-ZW, L-Ala-ZW, L-Val-ZW, L -Pro-ZW, two model proteins such as BP-TI (bovine pancreatic trypsin inhibitor) and PTP1B (protein tyrosine phosphatase 1B), as well as complexes of the PTP1B protein with inhibitors. The presented results show that the approach allows one to describe in detail and at the same time a holistic description of the hydration shell structure of biomolecules.

Efficient and Facile One-Pot Multi-Component Synthesis of Betti Bases Using Baker’s Yeast for the First Time

A green and facile synthesis of 1-(α-aminoalkyl)-2-naphthols, generally called Betti bases (BB) in the presence of Baker’s yeast (BY), acts as an efficient catalyst, and ethanol as a green solvent. In this methodology, the BY is used first time as a biocatalyst (enzyme). This protocol has some inherent advantages, such as mild reaction conditions, no environmental pollution, simple work up, no need of column chromatography, diversity of reactant and desired 1-(α-aminoalkyl)-2-naphthols (Betti bases) (4a-r) are obtained in good-to-excellent yields. This is the first report on Baker’s yeast-catalyzed (BYC) synthesis for BB. This present bio-catalytical route for synthesizing BB in the presence of biocatalysts like BY is anticipated to open a gateway to synthesized complexed biological active molecules counting BB.

Laser-induced graphene electrodes on polyimide membranes modified with gold nanoparticles for the simultaneous detection of dopamine and uric acid in human serum.

The level control of biological active molecules in human body fluids is important for the surveillance of several human diseases. Dopamine (DA) and uric acid (UA) are two important biomarkers of neurological and bone diseases, respectively. Design of sensitive and cost-effective sensors for their detection is an effervescent research field. We report on the straightforward design of laser-induced graphene electrodes (LIGEs) from the laser ablation of a polyimide substrate and their modification by electrochemical deposition of gold nanoparticles (AuNPs/LIGE) and their uses as chemosensors. Electrochemical investigations showed that the presence of gold nanoclusters onto the electrode surface improved the electrochemical surface area (ECSA) and the heterogenous electron transfer (HET) rate. Furthermore, the AuNPs/LIGEs can be used to detect simultaneously low concentrations of DA and UA in presence of ascorbic acid (AA)as an potentiallyinterfering substance at redox potentials of 300 mV, 230 mV and 450 mV and 91 mV, respectively, compared with the Ag/AgCl (3 M KCl) reference electrode in cyclic voltametric. The method displayed linear ranges varying from 2 to 20 μM and 5 to 50 μM, led to limits of detection of 0.37 μM and 0.71 μM for DA and UA, respectively. The AuNPs/LIGE was applied to simultaneously detect both analytes in scarcely diluted human serum with good recoveries. The data show that the recovery percentages ranged from 94% ± 2.1 to 102 % ± 0.5 and from 94% ±0.3 to 112% ± 1.4 for dopamine and uric acid, respectively. Thus, the AuNPs/LIGEs are promising candidates for the detection of other biologically active molecules such as drugs, pesticides, and metabolites.

Palladium-Catalyzed Dearomatization of Indoles with Alkynes: Construction of Spirocyclohexaneindolenines.

A palladium-catalyzed dearomatization of indoles with alkynes has been developed, providing an efficient route to access a variety of synthetically useful spirocyclohexaneindolenines in moderate to good yields. The current method features a simple catalytic system, operational simplicity, and good functional group compatibility, which will contribute substantially to the development of dearomatization to access spiro compounds. Besides, the ubiquitous existence of spiro molecules, including spirocyclohexaneindolenines, in drugs and biological active molecules suggests the potential application of this methodology in medicinal chemistry.

Phytochemical analysis of Different extract of Hyptis suaveolens(L.)Poit

Aromatic plants are the basin of secondary metabolites that are accountable for the plants medicinal efficacy and major origin of aromatic compound and essential oils. Now days due to richness of bioactive elements in plants they play a crucial role in production of enormously increasing herbal product. In the present study Hyptis suaveolens (L.)Poit from Mahodari ghat region were analysed for secondary metabolites by using plant parts (roots, leaves, stem and seed) and by using range of solvent from polar to non-polar. Many of different phytochemical Glycosides, Terpenoids, tannins, Flavonoids, alkaloids, coumarins, phlobatannins and phytosterols were found in methanolic extract of leaf and stem, seeds. While extract of hexane, Petroleum ether and chloroform exhibits presence of some of them. Obtained results show importance of biological active molecules for pharmaceutical and cosmetic industries. 
 Keywords Phytochemical, Secondary metabolites, bioactive compound

Exploring the Symmetry of Curvilinear Regression Models for Enhancing the Analysis of Fibrates Drug Activity through Molecular Descriptors

Quantitative structure-property relationship (QSPR) modeling is crucial in cheminformatics and computational drug discovery for predicting the activity of compounds. Topological indices are a popular molecular descriptor in QSPR modeling due to their ability to concisely capture the structural and electronic properties of molecules. Here, we investigate the use of curvilinear regression models to analyze fibrates drug activity through topological indices, which modulate lipid metabolism and improve the lipid profile. Our QSPR approach predicts the physicochemical properties of fibrates based on degrees and distances from topological indices. Our results demonstrate that topological indices can enhance the accuracy of predicting physicochemical properties and biological activities of molecules, including drugs. We also conducted density functional theory (DFT) calculations on the investigated derivatives to gain insights into their optimized geometries and electronic properties, including symmetry. The use of topological indices in QSPR modeling, which considers the symmetry of molecules, shows significant potential in improving our understanding of the structural and electronic properties of compounds.

Placenta exosomal miRNA-30d-5p facilitates decidual macrophage polarization by targeting HDAC9.

Pregnancy involves a wide range of adaptations in the maternal body. Maternal immune tolerance toward the foreign fetus is critical for a successful pregnancy. Decidual macrophages are the primary antigen-presenting and phagocytic cells responsible for antigen presentation and apoptotic cell removal. Their phenotype changes dynamically during pregnancy. Placenta-derived exosomes are small vesicles carrying active biological molecules such as microRNAs, proteins, and lipids. The placenta-derived exosomes have been implicated in endothelial cell activation, smooth muscle cell migration, and T-cell apoptosis, but it is unknown whether placenta-derived exosomes would affect the development and functions of decidual macrophages. In this study, we reported that placenta-derived exosomes stimulated macrophage polarization into alternatively activated (M2) macrophages. Mechanistically, miRNA-30d-5p from the placenta-derived exosomes induced macrophage polarization to the M2 phenotype by targeting histone deacetylase 9. Furthermore, the conditioned medium of placenta-derived exosome-treated macrophages promoted trophoblast migration and invasion. By contrast, the conditioned medium impaired the ability of endothelial cell tube formation and migration. Placenta-derived exosome-treated macrophages had no impact on T-cell proliferation. Together, we demonstrated that placenta-derived exosomes polarize macrophages to acquire a decidua-like macrophage phenotype to modulate trophoblast and endothelial cell functions.

Controlling the toxicity of biomass-derived difunctional molecules as potential pharmaceutical ingredients for specific activity toward microorganisms and mammalian cells.

A biomass-derived difuran compound, denoted as HAH (HMF-Acetone-HMF), synthesized by aldol-condensation of 5-hydroxyfurfural (HMF) and acetone, can be partially hydrogenated to provide an electron-rich difuran compound (PHAH) for Diels-Alder reactions with maleimide derivatives. The nitrogen (N) site in the maleimide can be substituted by imidation with amine-containing compounds to control the hydrophobicity of the maleimide moiety in adducts of furans and maleimide by Diels-Alder reaction, denoted as norcantharimides (Diels-Alder adducts). The structural effects on the toxicity of various biomass-derived small molecules synthesized in this manner to regulate biological processes, defined as low molecular weight (≤ 1000 g/mol) organic compounds, were investigated against diverse microbial and mammalian cell types. The biological toxicity increased when hydrophobic N-substitutions and C=C bonds were introduced into the molecular structure. Among the synthesized norcantharamide derivatives, some compounds demonstrated pH-dependent toxicities against specific cell types. Reaction kinetics analyses of the norcantharimides in biological conditions suggest that this pH-dependent toxicity of norcantharimides could arise from retro Diels-Alder reactions in the presence of a Brϕnsted acid that catalyzes the release of an N-substituted maleimide, which has higher toxicity against fungal cells than the toxicity of the Diels-Alder adduct. These synthetic approaches can be used to design biologically-active small molecules that exhibit selective toxicity against various cell types (e.g., fungal, cancer cells) and provide a sustainable platform for production of prodrugs that could actively or passively affect the viability of infectious cells.

Bonding of Neuropeptide Y on Graphene Oxide for Drug Delivery Applications to the Central Nervous System.

Nanoscale graphene-based materials (GBMs) enable targeting subcellular structures of the nervous system, a feature crucial for the successful engineering of alternative nanocarriers to deliver drugs and to treat neurodisorders. Among GBMs, graphene oxide (GO) nanoflakes, showing good dispersibility in water solution and being rich of functionalizable oxygen groups, are ideal core structures for carrying biological active molecules to the brain, such as the neuropeptide Y (NPY). In addition, when unconjugated, these nanomaterials have been reported to modulate neuronal function per se. Although some GBM-based nanocarriers have been tested both in vitro and in vivo, a thorough characterization of covalent binding impact on the biological properties of the carried molecule and/or of the nanomaterial is still missing. Here, a copper(I)-catalyzed alkyne-azide cycloaddition strategy was employed to synthesize the GO-NPY complex. By investigating through electrophysiology the impact of these conjugates on the activity of hippocampal neurons, we show that the covalent modification of the nanomaterial, while making GO an inert platform for the vectorized delivery, enhances the duration of NPY pharmacological activity. These findings support the future use of GO for the development of smart platforms for nervous system drug delivery.

Executive Editor-in-Chief’s introduction for This Special Issue

Executive Editor-in-Chief’s introduction for This Special Issue

Forest Biomass as a Promising Source of Bioactive Essential Oil and Phenolic Compounds for Alzheimer’s Disease Therapy

Alzheimer’s disease (AD) is the most common neurodegenerative disorder affecting elderly people worldwide. Currently, there are no effective treatments for AD able to prevent disease progression, highlighting the urgency of finding new therapeutic strategies to stop or delay this pathology. Several plants exhibit potential as source of safe and multi-target new therapeutic molecules for AD treatment. Meanwhile, Eucalyptus globulus extracts revealed important pharmacological activities, namely antioxidant and anti-inflammatory properties, which can contribute to the reported neuroprotective effects. This review summarizes the chemical composition of essential oil (EO) and phenolic extracts obtained from Eucalyptus globulus leaves, disclosing major compounds and their effects on AD-relevant pathological features, including deposition of amyloid-β (Aβ) in senile plaques and hyperphosphorylated tau in neurofibrillary tangles (NFTs), abnormalities in GABAergic, cholinergic and glutamatergic neurotransmission, inflammation, and oxidative stress. In general, 1,8-cineole is the major compound identified in EO, and ellagic acid, quercetin, and rutin were described as main compounds in phenolic extracts from Eucalyptus globulus leaves. EO and phenolic extracts, and especially their major compounds, were found to prevent several pathological cellular processes and to improve cognitive function in AD animal models. Therefore, Eucalyptus globulus leaves are a relevant source of biological active and safe molecules that could be used as raw material for nutraceuticals and plant-based medicinal products useful for AD prevention and treatment.

SYNTHESIS, REACTIONS, AND PHARMACOLOGICAL APPLICATIONS OF 2-AMINOBENZIMIDAZOLES: AN UPDATE

Many drug molecules comprises of benzo fused heterocycles with two nitrogen atoms, that is, benzimidazole and its derivatives. Many biological active molecules contain that 2-aminobenzimidazole cores are among the foremost common structural components in medicinal chemistry. 2-aminobenzimidazole and its derivative have wide range of biological and pharmaceutical activities. In this review, the authors summarize synthesis, various chemical reactions, and biological activities of 2-aminobenzimidazole and its derivative.

Computational studies with flavonoids and terpenoids as BRPF1 inhibitors: in silico biological activity prediction, molecular docking, molecular dynamics simulations, MM/PBSA calculations

ABSTRACT The BRPF1 protein is encoded by the BRPF1 gene. In addition, the BRPF1 gene is known to be upregulated in leukaemia. Recent studies have shown that it is also overexpressed in hepatocellular carcinoma (HCC) as well. Therefore, BRPF1 is a significant target for anti-cancer drug development studies, especially on HCC. 40 terpenoids and flavonoids were chosen because of their anticancer properties given in the literature. In this study, the biological activity of molecules was also investigated with in silico structure-activity relationship analysis. In addition, interactions between a series of terpenoids and flavonoids and the BRPF1 protein were investigated by molecular docking and molecular dynamics simulations. The energy change caused by the interactions of BRPF1 with different compounds was also evaluated by MM/PBSA calculations. It has been revealed that compound 5 (−9.2 kcal/mol), a kind of secoclerodane type diterpenoid, has a higher affinity both compared to other flavonoids and terpenoids, and 9F9 (−7.9 kcal/mol), a selective BRPF1 inhibitor. The study presented in this article demonstrates that compound 5, as a natural product, could form a chemical scaffold for the development of selective BRPF1 bromodomain inhibitors.

M-polynomial and neighborhood M-polynomial of some concise drug structures: Azacitidine, Decitabine and Guadecitabine

A topological index is a mathematical value associated with a graph. In chemometrics, biomedicine and bioinformatics, it is widely used to predict various physicochemical properties and biological activities of molecules. Neighborhood M-polynomial (NM-polynomial) is one of such polynomials which is used to obtain many degree-based topological indices. Azacitidine, Decitabine (5-aza-20-deoxycytidine) and Guadecitabine (SGI-110) are hypomethylating agents which are used for the treatments of patients with higher-risk myelodysplastic syndromes, chronic myelomonocytic leukemia and acute myeloid leukemia which are not suitable for in-depth treatments such as induction chemotherapy. In this work, we compute some degree-based and neighborhood degree sum-based indices of the three aforementioned drugs in unified manner by using M-polynomial and NM-polynomial. The findings may aid in the development of novel cancer treatment medicines.

Machine learning methods for predicting the biological activities of molecules in high diverse databases

Machine learning methods for predicting the biological activities of molecules in high diverse databases

Control of the structure and of the release profile of biological active molecules from materials prepared via sol-gel

Control of the structure and of the release profile of biological active molecules from materials prepared via sol-gel