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Abstract Graphene-based nanomaterials have been proved to be robust sorbents for efficient removal of environmental contaminants including arsenic (As). Biobased graphene oxide (bGO-P) derived from sugarcane bagasse via pyrolysis, GO-C via chemical exfoliation, and magnetite nanoparticles (FeNPs) via green approach using Azadirachta indica leaf extract were synthesized and characterized by Ultraviolet-Visible Spectrophotometer (UV-vis.), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), mean particle size and Scanning electron microscopy (SEM) along with Energy dispersive spectroscopy (EDX) analysis. Compared to cellulose and hemicellulose, the lignin fraction was less in the precursor material. The GOC, bGO-P and FeNPs displayed maximum absorption at 230, 236, and 374 nm, respectively. FTIR spectrum showed different functional groups (C-OH, C-O-C, COOH and O-H) modifying the surfaces of synthesized materials. Graphene based nanomaterials showed clustered dense flakes of GO-C and thin transparent flakes of bGO-P. Elemental composition by EDX analysis of GO-C (71.26% C and 27.36% O), bGO-P (74.54% C and 24.61% O) and FeNPs (55.61% Fe, 4.1% C and 35.72% O) confirmed the presence of carbon, oxygen, and iron in synthesized nanomaterials. Sorption study was conducted with soil amended with different doses of synthesized nanomaterials (10, 50 and 250 mg) and exposed to 100, 300 and 500 ppm of As. Arsenic concentrations were estimated by colorimetry and atomic absorption spectroscopy (AAS). GO-C, bGO-P, and FeNPs showed substantial As removal efficiency i.e., 81 to 99.3%, 65 to 98.8% and 73.1–89.9%, respectively. Green synthesis of bGO-P and magnetite nanoparticles removed substantial amounts of As compared to GO-C and can be effectively deployed for As removal or immobilization. Higher and medium sorbent doses (250 and 50 mg) exhibited greater As removal and data was best fitted for Freundlich isotherm evidencing favorable sorption. Nevertheless, at low sorbent doses, data was best fitted for both models. Newly synthesized nanomaterials emerged as promising materials for As removal strategy for soil nano-remediation and can be effectively deployed in As contaminated soils.

Abstract Green nanotechnology has significant potential for use in agriculture particularly due to their antifungal properties, ability to control fungal diseases and reduce the reliance on chemical fungicides. Biotic stresses in agriculture have caused widespread damage worldwide, and green NPs provided eco-friendly alternatives to traditional chemical treatments, which are frequently toxic and harmful to the ecosystem. Green NPs could become an important tool in modern agricultural practices and environmental remediation if appropriate research is conducted to identify cost-effective production methods as well as safe and sustainable applications. In order to understand the potential of green NPs for sustainable agriculture and identify potential risks, research is ongoing into the effectiveness in agriculture sectors. Research update on green NPs is presented in this paper using data published on science direct over the last 15 to 20 years to clarify and understand the antifungal mechanisms of green metallic NPs, carbon and graphene nanotubes, nanocomposites as well as other type of nanomaterials. These green NPs are found to be more effective against pathogens on crops and humans than conventional fungicide approaches. They are very effective against fungi that affect cereal crops, including Fusarium oxysporum, Botrytis cinerea, and Candida species, etc. The green NPs developed using green synthesis methods are both cost-effective and environmentally friendly. Moreover, research is also required to identify the best methods for applying green NPs for crop production and sustainable agriculture. Furthermore, research should be undertaken to establish the most cost-effective methods of making and deploying green nanoparticles at a large field size study where there is fungal attack that diminishes agricultural output and affects global crop production. Graphical Abstract

Abstract This study investigated the adsorption of Oxytetracycline (OTC) from pharmaceutical wastewater using a kappa carrageenan based hydrogel (KPB). The aim of the present study was to explore the potential of KPB for long-term pharmaceutical wastewater treatment. A sustainable adsorbent was developed to address oxytetracycline (OTC) contamination. The hydrogel’s structural and adsorption characteristics were examined using various techniques like Scanning Electron Microscope (SEM), Fourier Transform Infrared (FTIR), X-ray powder diffraction (XRD), and kinetic models. The results revealed considerable changes in the vibrational modes and adsorption bands of the hydrogel, suggesting the effective functionalization of Bentonite nano-clay. Kappa carrageenan based hydrogel achieved the maximum removal (98.5%) of OTC at concerntration of 40 mg/L, pH 8, cotact time of 140 min and adsorbent dose of 0.1 g (KPB-3). Adsorption of OTC increased up to 99% with increasing initial concentrations. The study achieved 95% adsorption capacity for OTC using a KPB film at a concentration of 20 mg/L and a 0.1 g adsorbent dose within 60 min. It also revealed that chemisorptions processes outperform physical adsorption. The Pseudo-Second-Order model, which emphasized the importance of chemical adsorption in the removal process, is better suited to represent the adsorption behavior. Excellent matches were found that R2 = 0.99 for KPB-3, R2 = 0.984 for KPB-2 and R2 = 0.989 for KPB-1 indicated strong chemical bonding interactions. Statisctical analysis (ANOVA) was performed using SPSS (version 25) and it was found that pH and concentration had significant influence on OTC adsorption by the hydrogel, with p-values less than 0.05. The study identified that a Kappa carrageenan-based hydrogel with bentonite nano-clay and polyvinyl alcohol (PVA) can efficiently remove OTC from pharmaceutical effluent, with a p-value of 0.054, but weak positive linear associations with pH, temperature, and contact time. This research contributed to sustainable wastewater treatment and environmental engineering.

Abstract Cardiovascular diseases, including heart failure, stroke, and hypertension, affect 608 million people worldwide and cause 32% of deaths. Combination therapy is required in 60% of patients, involving concurrent Renin–Angiotensin–Aldosterone-System (RAAS) and Neprilysin inhibition. This study introduces a novel multi-target in-silico modeling technique (mt-QSAR) to evaluate the inhibitory potential against Neprilysin and Angiotensin-converting enzymes. Using both linear (GA-LDA) and non-linear (RF) algorithms, mt-QSAR classification models were developed using 983 chemicals to predict inhibitory effects on Neprilysin and Angiotensin-converting enzymes. The Box-Jenkins method, feature selection method, and machine learning algorithms were employed to obtain the most predictive model with ~ 90% overall accuracy. Additionally, the study employed virtual screening of designed scaffolds (Chalcone and its analogues, 1,3-Thiazole, 1,3,4-Thiadiazole) applying developed mt-QSAR models and molecular docking. The identified virtual hits underwent successive filtration steps, incorporating assessments of drug-likeness, ADMET profiles, and synthetic accessibility tools. Finally, Molecular dynamic simulations were then used to identify and rank the most favourable compounds. The data acquired from this study may provide crucial direction for the identification of new multi-targeted cardiovascular inhibitors.

Abstract The current research focuses on the development of Ag–ZnO heterostructures through a “bottom-up” approach involving the assembly and extraction of Aloe barbadensis Miller gel. These heterostructures composed of metals/semiconductor oxide display distinct and notable optical, electrical, magnetic, and chemical properties that are not found in single constituents and also exhibit photocatalytic applications. These synthesized heterostructures were characterized by XRD, FTIR, SEM, and UV–visible spectroscopy. The high peak intensity of the Ag/ZnO composite shows the high crystallinity. The presence of Ag–O, Zn–O, and O–H bonding is verified using FTIR analysis. SEM analysis indicated the formation of spherical shapes of Ag/ZnO heterostructures. The Zn, O, and Ag elements are further confirmed by EDX analysis. Ag–ZnO heterostructures exhibited excellent photocatalytic activity and stability against the degradation of tubantin red 8BL dye under visible light irradiation.

A series of methoxy substituted pyrazole based pyrazoline derivatives (4a-j) were synthesized in good to excellent yield from corresponding pyrazole-chalcones (3a-j). All synthesized derivatives were characterized and screened for their in vitro anti-inflammatory, antioxidant, antidiabetic, and antibacterial activities. Among the series, compounds 4f, 4j, 4a, and 4i showed better anti-inflammatory activity as compared to diclofenac sodium. In DPPH free radical scavenging assay, all the compounds were shown excellent activity and moderate to good activity in SO and NO free radical scavenging assay as compared to standard ascorbic acid. Antibacterial screening of synthesized pyrazolines showed that compounds 4f and 4j have significant antibacterial activity. The compounds 4j, 4f, 4h, 4a, and 4c have shown comparable inhibition of alpha-amylase enzyme leading to good antidiabetic activity as compared to standard acarbose. Molecular docking studies suggest that these compounds have strong binding with COX-2 and alpha-amylase enzyme due to significant capability of aromatic and hydrophobic interaction. The outstanding results of reported compounds in all biological screening will pave the way for the design of new drug candidate bearing pyrazole moiety.

Monoamine oxidase B (MAO-B) plays a pivotal role in the deamination process of monoamines, encompassing crucial neurotransmitters like dopamine and norepinephrine. The heightened interest in MAO-B inhibitors emerged after the revelation that this enzyme could potentially catalyze the formation of neurotoxic compounds from endogenous and exogenous sources. Computational screening methodologies serve as valuable tools in the quest for novel inhibitors, enhancing the efficiency of this pursuit. In this study, 43 acefylline derivatives were docked against the MAO-B enzyme for their chemotherapeutic potential and binding affinities that yielded GOLD fitness scores ranging from 33.21 to 75.22. Among them, five acefylline derivatives, namely, MAO-B14, MAO-B15, MAO-B16, MAO-B20, and MAO-B21, displayed binding affinities comparable to the both standards istradefylline and safinamide. These derivatives exhibited hydrogen-bonding interactions with key amino acids Phe167 and Ile197/198, suggesting their strong potential as MAO-B inhibitors. Finally, molecular dynamics (MD) simulations were conducted to evaluate the stability of the examined acefylline derivatives over time. The simulations demonstrated that among the examined acefylline derivatives and standards, MAO-B21 stands out as the most stable candidate. Density functional theory (DFT) studies were also performed to optimize the geometries of the ligands, and molecular docking was conducted to predict the orientations of the ligands within the binding cavity of the protein and evaluate their molecular interactions. These results were also validated by simulation-based binding free energies via the molecular mechanics energies combined with generalized Born and surface area solvation (MM-GBSA) method. However, it is necessary to conduct in vitro and in vivo experiments to confirm and validate these findings in future studies.

The combination of heterocycles renders a new possibility to synthesize multicyclic compounds having improved biological activities. Furo[3,2-b]pyridine is a fused heterocyclic ring system comprising a furan ring attached at the third and second positions of pyridine. These heterocyclic compounds can be easily synthesized from versatile starting materials including pyridine, furan, benzofuran, and benzopyridine via cycloaddition, cycloisomerization, multicomponent, cross-coupling, and Dakin-type reactions by utilizing microwave, copper, and palladium based catalysts. Among the chemical transformations of furo[3,2-b]pyridine derivatives, the review covered acetylation, addition, condensation, chlorination, Suzuki coupling, Vilsmeier-Haack reaction, and nucleophilic substitution reactions. Furo[3,2-b]pyridine has attracted remarkable attention from researchers due to its wide range of pharmacological and biological applications as antibiotic, antiviral, antifungal, anticancer, inhibitors of nicotinic acetylcholine receptors, CLKs, e1F4A, DYRKIA, α-glucosidase and β-glucosidase. The purpose of the review is to discuss the chemistry of the title reported during 2019–2024.

Carbazole is a heterocyclic aromatic organic compound that has vast applications in pharmaceuticals, and in biological and material sciences. Carbazole derivatives show various biological activities such as antibiotic, anti-inflammatory, anti-tumor and anti-oxidant activities etc. Synthesis of N-arylated carbazoles has become a major area of interest for scientists due to their applications in organic light-emitting diodes, dye-sensitized solar cells, and other organic electronics. The N-arylated carbazoles have unique properties such as high thermal stability, wide band gap, and excellent electrical and optical properties. The methods used for the N-arylation of carbazoles include transition metal-catalyzed reactions and metal-free reactions. The most common and classical methods for the N-arylation of carbazoles are copper-catalyzed Ullmann coupling reactions, while palladium, nickel, and iron catalysts are also used. This review focuses on all the synthetic methods used for the N-arylation of carbazoles and their applications.

Until today, microbial infections epitomize a serious universal health threat. Subsequently, developing a potential antimicrobial prototype remains an urgent, global necessity. Despite several reports discussing the biological utility of some bis-thiazoles, the use of bis-dihydrazothiazoles and their corresponding metal chelates as potent antimicrobials, is yet to be explored. The current report outlines an attempt to fill that void by representing a successful synthesis of a new class of bis-dihydrazothiazoles as well as three of their transition metal chelates and their use as potential antimicrobials. This report presents the design of some novel hydroxy-tagged bis-dihydrazothiazoles 6a-e and bis-dihydrazothiazolones 9a-e via the reaction of a bis-aldehyde thiosemicarbazone 3, as a common synthetic precursor, with two groups of hydrazonoyl halide derivatives 4a-e and 7a-e. The chelation affinity of these novel bis-dihydrazothiazoles to behave as neutral tridentate ligands coordinating to the metal ions; Fe(III), Co(II), or Zn(II) through azomethine-N, thiazole-S, and azo-N atoms to form metal complexes with a metal/ligand ratio of 2:1 was confirmed. In-vitro, antimicrobial screening of the novel hydroxy-tagged bis-dihydrazothiazole derivatives, as well as a selected group of their transition metal chelate complexes [M2L], was inspected, and the data were measured in comparison to those of ketoconazole and gentamycin as antimicrobial reference standards. Most bis-dihydrazothiazoles 6a-e and bis-dihydrazothiazolones 9a-e showed decent to excellent antimicrobial activities against the screened microbes, but the chloro-substituted bis dihydrazothiazole derivatives 6c and 9c showed exceptional inhibition of Bacillus subtilis (20 mm), Escherichia coli (25 mm), and Candida albicans (19 mm), and Salmonella typhimurium (19 mm), respectively. Additionally, amongst the three synthesized metal complexes [M2L], only the zinc complex, [Zn2L] showed remarkable inhibition of both Staphylococcus aureus (21 mm) and Salmonella typhimurium (19 mm) compared to the reference standard Gentamycin, and was more potent than the free ligand, 6a itself (no activity and 11 mm respectively). Antimicrobial inspection was assessed by the agar well diffusion assay method against all bacterial and fungal strains. Magnetic moment, diffused reflectance, FT-IR, 1H NMR, molar conductivity, thermogravimetric analysis (TGA), X-ray diffraction (XRD), and scanning electron microscope (SEM) were among the many techniques used to elucidate the structures of all novel hydroxy-tagged bis-heterocyclic ligands and their metal chelate complexes.

Many human disorders include NF-kB signaling pathways, making IKK a therapeutic target in cancer treatment. Inflammatory illnesses and cancer are examples. COVID-19 is one of several triggers that stimulate NF-kB signaling. The activation of the NF-kB pathway is necessary for COVID-19 to cease its development. To learn more about the mechanism and structural features essential to IKK inhibition (IC50), molecular modeling studies have been undertaken on experimentally reported 503. QSAR analysis explores certain reported and hidden structural features critical for IKKβ inhibition. The OECD guidelines guided the construction of the QSAR model, which achieved all the endorsed threshold values for all validation parameters (R2tr:0.81, R2LMO:0.80, and R2ext:0.78). The present QSAR study shows that IKK inhibitory activity is linked to the following structural features: lipophilic hydrogen atoms within 2 A units of the molecule's center of mass; ring nitrogen atoms within one bond of planar nitrogen atoms; ring carbon atoms exactly four bonds from the non-ring nitrogen atoms; planar nitrogen atoms exactly four bonds from sp2 hybridized carbon atoms; and so on. Pharmacophore modeling highlighted QSAR-identified structural characteristics. To investigate binding, we docked all 503 molecules. The observation indicates that the QSAR and molecular docking/pharmacophore modeling findings are in agreement. Following this, we conducted 200 ns of molecular dynamics simulation to validate the molecular docking protocol. MMGBSA analysis determined the binding energy of the dock complex. Thus, the current study found unique pharmacophoric properties that may assist in optimizing lead/hit compounds for anti-IKKβ activity.

The study focuses on green methodologies in synthetic organic chemistry, emphasizing the use of thiamine hydrochloride (Vitamin B1) as an eco-friendly catalyst for synthesizing hydrazono-thiazolones. These compounds serve as versatile core units with various therapeutic activities, including anti-HIV, anti-tubercular, antifungal, antiviral, and anticancer properties. Building on prior research involving sustainable barium oxide-chitosan nanocomposite catalysts, this novel green synthetic approach contributes to the sustainable synthesis of bioactive heterocycles. The synthesized compounds 6a-l were tested in vitro against different bacterial species, revealing notable activity against Gram-positive and Gram-negative bacteria. The MIC investigation showed that compounds 6d, 6e, 6j, and 6k have broad-spectrum antibacterial potential, with 6j and 6k being especially effective, their MICs near those of ciprofloxacin, highlighting their strong antibacterial capabilities. Molecular docking studies predicting the binding mode of the most potent substances to Escherichia coli DNA gyrase (PDB ID 4DUH) aligned well with in vitro studies, confirming the new ligands’ potency as potential antimicrobial agents. In silico investigations for the most potent substances revealed a favorable ADME profile, suggesting promising pharmacological properties. This research contributes to both sustainable synthesis and potential therapeutic applications of hydrazono- thiazolone derivatives.

The urease enzyme is recognized as a valuable therapeutic agent for treating the virulent Helicobacter pylori bacterium because of its pivotal role in aiding the colonization and growth of the bacterium within the gastric mucosa. In order to control the harmful consequences of bacterial infections, urease inhibition presents itself as a promising and effective approach. The current research aimed to synthesize pyridylpiperazine-based carbodithioate derivatives 5a–5n and 7a–7n that could serve as potential drug candidates for preventing bacterial infections through urease inhibition. The synthesized carbodithioate derivatives 5a–5n and 7a–7n were explored to assess their ability to inhibit the urease enzyme after their structural explication by gas chromatography–mass spectrometry (GC-MS). In the in vitro evaluation with thiourea as a standard drug, it was observed that all the synthesized compounds exhibited significant inhibitory activity compared to the reference drug. Among the compounds tested, 5j (bearing an o-tolyl moiety) emerged as the most effective inhibitor, displaying strong urease inhibition with an IC50 value of 5.16 ± 2.68 μM. This IC50 value is notably lower than that of thiourea (23 ± 0.03 μM), indicating the significantly most potent potential of inhibition. In molecular docking of 5j within the active site of urease, numerous noteworthy interactions were identified.

The urgent need to address the severe environmental risk posed by chromium-contaminated industrial wastewater necessitates the development of eco-friendly cleanup methodologies. Utilizing the Ficus benghalensis plant extracts, the present study aims to develop green zinc oxide nanoparticles for the removal of Cr metal ions from wastewater. The leaves of Ficus benghalensis, often known as the banyan tree, were used to extract a solution for synthesizing ZnO NPs. These nanoparticles were developed with the goal of efficiently eliminating chromium (Cr) from industrial effluents. Batch studies were carried out to assess the efficiency of these synthesized ZnO NPs in treating leather industrial effluent, with aiming for optimal chromium removal. This involved measuring the nanoparticles' capacity to adsorb Cr ions from wastewater samples by comparing chromium levels before and after treatment. Removal efficiency for Cr was estimated through the batches such as optimization of pH, contact time, initial Cr concentration and sorbent dose of ZnO NPs were of the batches. These synthesized ZnO NPs were found to be successful in lowering chromium levels in wastewater to meet permissible limit. The nanoparticles exhibited their highest absorption capacity, reaching 94 % (46 mg/g) at pH 4, with a contact time of 7 hours with the optimum sorbent dose of 0.6 g/L. Hence, the excellent adsorption capabilities of these nanoparticles, together with their environmentally benign manufacturing technique, provide a long-term and efficient solution for chromium-contaminated wastewater treatment. Its novel nature has the potential to significantly improve the safety and cleanliness of water ecosystems, protecting the both i.e. human health and the environment.

Calcium carbonate nanoparticles (CaCO3) have been found to exhibit unique properties that show their potential to be used in various therapies. Green synthesis of CaCO3 has been progressively gaining ac-ceptance due to its cost-effectiveness and energy-efficient nature. In the current study, different extracts of Ailanthus altissima were used to synthesize the calcium carbonate nanoparticles the synthesis and characterization of CCNPs were confirmed by using Fourier Transform Infra-Red spectroscopy, UV-Vis spectroscopy, and Scanning Electron Microscopy (SEM). The antioxidant activities (hydrogen peroxide, phosphomolydbenum, and ferric reducing) of calcium carbonate nanoparticles were affirmed by a good range of percentages of inhibition against free radical scavenging. The antidebate assays of CCNPs were observed by in-vitro and in silico approaches in a range at various concentrations while maximum inhibition occurred. In conclusion, the current study depicted that conjugated CaCO3 with A. altissima has a good potential to cure oxidative stress and Type II diabetes and could be used in the future as biogenic nanomedicine for the treatment of other metabolic diseases.

Background: According to the International Diabetes Federation, there will be 578 million individuals worldwide with diabetes by 2030 and 700 million by 2045. One of the promising drug targets to fight diabetes is α-glucosidase (AG), and its inhibitors may be used to manage diabetes by reducing the breakdown of complex carbohydrates into simple sugars. The study aims to identify and validate potential AG inhibitors in natural sources to combat diabetes. Methods: Computational techniques such as structure-based virtual screening and molecular dyncamic simulation were employed to predict potential AG inhibitors from compounds of Oroxylum indicum. Finally, in silico results were validated by in vitro analysis using n-butanol fraction of crude methanol extracts. Results: The XP glide scores of top seven hits OI_13, OI_66, OI_16, OI_44, OI_43, OI_20, OI_78 and acarbose were –14.261, –13.475, –13.074, –13.045, –12.978, –12.659, –12.354 and –12.296 kcal/mol, respectively. These hits demonstrated excellent binding affinity towards AG, surpassing the known AG inhibitor acarbose. The MM-GBSA dG binding energies of OI_13, OI_66, and acarbose were −69.093, −62.950, and −53.055 kcal/mol, respectively. Most of the top hits were glycosides, indicating that active compounds lie in the n-butanol fraction of the extract. The IC50 value for AG inhibition by n-butanol fraction was 248.1 μg/ml, and for that of pure acarbose it was 89.16 μg/ml. The predicted oral absorption rate in humans for the top seven hits was low like acarbose, which favors the use of these compounds as anti-diabetes in the small intestine. Conclusion: In summary, the study provides promising insights into the use of natural compounds derived from O. indicum as potential AG inhibitors to manage diabetes. However, further research, including clinical trials and pharmacological studies, would be necessary to validate their efficacy and safety before clinical use.

The serine hydrolase family includes serine proteases. It is essential for hydrolyzing protein peptide bonds and breaking them. The urokinase-type plasminogen activator (uPA) selectively binds to the uPAR on numerous cell types, including cancer cells. Pericellular proteolysis of cell-bound proteins requires this interaction. High uPA and uPAR levels regularly worsen cancer prognoses. Thus, small chemical active-site inhibitors that block uPA may diminish cancer cell invasion and metastasis. In compliance with Organization for Economic Corporation and Development guidelines, this research performed a complete Quantitative structure activity relationship analysis of sulfonamide compounds as Urokinase-type Plasminogen Activator inhibitors. Py-Descriptors were used for this investigation. PyDescriptor uses PyMOL standards and idioms to calculate 11,145 simple molecular descriptors. This plugin calculates molecular descriptors irrespective of molecular representation properties like atom numbering or labelling, spatial reference frame, translational and rotational invariance, etc. The investigation sought to find essential and hidden structural characteristics that regulate sulfonamide-type drugs' Urokinase-type Plasminogen Activator Inhibitory action. Twenty-eight sulfonamide chemicals are used in the Quantitative structure activity relationship study to generate statistically robust and highly predictive univariate and multivariate models. All models were thoroughly evaluated and meet several statistical parameter thresholds (e.g., R2 =0.9259–0.9280, Q2Loo= 0.8579–0.8558, Q2LMO= 0.8013–0.7865). The analysis reveal that occurance of ring carbon atoms exactly at 3 A0 from carbon atom, number of negatively charged atoms from sulphur atoms within 5 bonds, presence of hydrogen atom exactly at 3 bonds from donar atoms, presence of carbon atom exactly at 4 A0 from donar atom, presence of acceptor atom exactly at 5 A0 from sulphur atom and sum of partial charges of lipo atoms within 6 bonds from sulphur atom are important pharmacophoric features for Urokinase-type Plasminogen Activator Inhibition binding affinity. Thus, the developed Quantitative structure activity relationship study has an equilibrium of quantitative and qualitative tactics. The results could be useful for future optimizations of sulfonamide analogues.

In the existing effort, a dataset of 309 experimentally screened molecules for in vitro (Ki) agonist potential for Prostaglandin E2 (PGE2) receptor 2 subtype (EP2), which is a metabolite of arachidonic acid that binds with and regulates cellular responses to PGE2, was investigated in the QSAR (Quantitative structure–activity relationship) study. A six-parameter QSAR model was developed that meets the specified values ​​for internal and external validation as well as random parameters such as R2tr = 0.808, Q2LMO = 0.794, R2ex = 0.781. Insightful and quantitative opinion reveals several underappreciated and distinct structural features that are responsible for the agonist potency of these molecules on Prostaglandin EP2 receptor such as; the hydrogen atom is correct 2 bonds from the donor atom, the sp2 hybridized carbon atom is correct 2 bonds from the cyclic nitrogen atom, and so on. The developed QSAR model captures the narrative as well as the novel pharmacophoric features. The QSAR effect was further demonstrated using the reported crystalline buildings of CP533536 with the Prostaglandin EP2 receptor activity. The evaluation led to the identification of valuable new pharmacophoric properties that will be used to optimize lead compounds in the future.

The increase in antibiotic-resistant bacteria presents a significant risk to worldwide public health, emphasizing the necessity of novel approaches to address infections. Quorum sensing, an essential method of communication among bacteria, controls activities like the formation of biofilms, the production of virulence factors, and the synthesis of secondary metabolites according to the number of individuals in the population. Quorum quenching, which interferes with these processes, emerges as a vital approach to diminish bacterial virulence and prevent biofilm formation. Nanocarriers, characterized by their small size, high surface-area-to-volume ratio, and modifiable surface chemistry, offer a versatile platform for the disruption of bacterial communication by targeting various stages within the quorum sensing pathway. These features allow nanocarriers to infiltrate biofilms, disrupt cell membranes, and inhibit bacterial proliferation, presenting a promising alternative to traditional antibiotics. Integrating nanocarrier-based systems into combination therapies provides a multi-pronged approach to infection control, enhancing both the efficacy and specificity of treatment regimens. Nonetheless, challenges related to the stability, safety, and clinical effectiveness of nanomaterial-based antimicrobial treatments remain. Continued research and development are essential to overcoming these obstacles and fully harnessing the potential of nano-antimicrobial therapies. This review emphasizes the importance of quorum sensing in bacterial behavior and highlights the transformative potential of nanotechnology in advancing antimicrobial treatments, offering innovative solutions to combat antibiotic-resistant pathogens.

N-Arylpyrazoles are important building blocks in many biologically active compounds, natural products, pharmaceuticals, and industries. It is an important moiety of various drugs and exhibits extensive biological activities viz., antibiotic, anticancer, antifungal, anti-inflammatory, anti-coagulant, analgesic, antipyretic, anti-depressant, insecticidal, and hyperglycemic activities. Various protocols have been designed for the synthesis of N-arylpyrazoles facilitated by a wide variety of metal-based catalysts at high or room temperature, metal free reactions, various named reactions, multicomponent reactions, and those occurring under different electromagnetic radiations. Various ligands are found to promote Cu-catalyzed N-arylation of pyrazole under mild conditions in short time. This review describes the synthesis and biological applications of N-arylpyrazole derivatives reported during 2019–2023.

The rivers are severely contaminated by human activities due to its massive outflow and industrial effluents. Three economically significant fish species Sperata seenghala, Wallago attu, and Cyprinus carpio from the river water were selected for the assessment of heavy metals (HMs). The edible part of the collected fish from the river sampling sites were analyzed to determine the metal concentrations and potential health risks to humans. The Atomic Absorption Spectroscopy (AAS) technique was used to measure HMs including lead (Pb), chromium (Cr), and copper (Cu) for both water and fish samples. Order of HMs in the fish was found as Pb > Cd > Cr. Levels of HMs in all species were found higher than the European Commission (EC) recommended acceptable levels. The metal pollution index (MPI) indicates that W. attu and S. seenghala, two highly consumed fish species, have accumulated HMs in higher concentrations. Wallago attu has the highest bioaccumulation factor (BAF) for both Pb and Cd permissible levels. For adult and children, the Hazard Index (HI) and Targeted Hazard Quotient (THQ) values were less than 1, which indicated that there would be no non-carcinogenic health consequences. Carcinogenic risk (CR) exposure to Pb, Cd, and Cr for all consumers was found to be higher than the permitted limit (10−6-10−4), while children were found more vulnerable than adults in terms of CR values. The study findings identified several sources of contaminants in the area, including agricultural waste, lubricant usage, and electroplating material production dumping near into the river water. Based on the results of the analysis, metal concentrations exceeded the thresholds for carcinogenic health risks, indicating that fish from the area are generally unsafe to consume. Therefore, immediate action must be taken to reduce or prevent the discharge of contaminants into the river. Additionally, regular monitoring of the river's water quality should be conducted to control the contamination of water.

Natural product synthesis is an important area of chemical study having various prospects for medicinal, industrial, and agricultural industry. Grignard reaction was developed as a flexible and necessary tool for the production of complex organic compounds in synthetic procedures. Additionally, the synthetic flexibility of the Grignard reaction facilitates its usage in the construction of more complicated ring frameworks and stereoselective transformations. It has been substantially applied in natural product synthesis, demonstrating its effectiveness in the generation of crucial C-C, C-X bonds and the development of intricate molecular structures. Use of Grignard reaction has been significantly studied towards the synthesis of biologically active natural products such as terpenoids, polyketides, alkaloids and amino acids. This review outlines the numerous instances where Grignard reagents have been exploited in the synthesis of notable natural products since past two years.

4-Acetylpyridine 1 and malononitrile 2 were allowed to react in a 3MCRs with dimedone 3a or cyclohexa-1,3-dione 3b under reflux to afford 4-methyl-4-(pyridin-4-yl)-5,6,7,8-tetrahydro-4H-chromene derivatives 4a,b respectively. The mechanism of the reaction has been studied and the structures elucidated by analytical, spectral as well as X-ray crystallographic data. Heterocyclic compounds find widespread application in pharmaceutical and agrochemical products. Docking analyses were performed on the synthesized compounds to assess their binding modes with various amino acids of the target protein tubulin (PDB Code - 1SA0). The results indicated promising binding scores for compounds 4a and 4b, suggesting a strong affinity for the tubulin binding site. Finally, ADMET for the synthesized compounds 4a, 4b, 5, 8a and 8b were carried out. The drug likeness and pharmacokinetic properties of the prepared compounds were also evaluated. Notably, all of the novel compounds adhered to Lipinski's rule (Ro5) without any violations.

Theophylline, a nitrogen-containing heterocycle, serves as a promising focal point for medicinal researchers aiming to create derivatives with diverse pharmacological applications. In this work, we present an improved synthetic method for a range of theophylline-1,2,4-triazole-S-linked N-phenyl acetamides (4a‒g) utilizing ultrasound-assisted synthetic approach. The objective was to assess the effectiveness of synthesized theophylline-1,2,4-triazoles (4a‒g) as inhibitors of HCV serine protease and as antibacterial agents against B. subtilis QB-928 and E. coli AB-274. Theophylline-1,2,4-triazoles were obtained in good to excellent yields (69%–95%) in a shorter time than conventional approach. 4-Chlorophenyl moiety containing theophylline-1,2,4-triazole 4c displayed significantly higher inhibitory activity against HCV serine protease enzyme (IC50 = 0.015 ± 0.25 mg) in comparison to ribavirin (IC50 = 0.165 ± 0.053 mg), but showed excellent binding affinity (−7.55 kcal/mol) with the active site of serine protease, better than compound 4c (−6.90 kcal/mol) as well as indole-based control compound 5 (−7.42 kcal/mol). In terms of percentage inhibition of serine protease, 2-chlorophenyl compound 4b showed the maximum percentage inhibition (86%), more than that of the 3,4-dichlorophenyl compound 4c (76%) and ribavirin (81%). 3,4-Dimethylphenyl-based theophylline-1,2,4-triazole 4g showed the lowest minimum inhibitory concentration (MIC = 0.28 ± 0.50 μg/mL) against the B. subtilis bacterial strain as compared to the standard drug penicillin (MIC = 1 ± 1.50 μg/mL). The other 4-methylphenyl theophylline-1,2,4-triazole 4e (MIC = 0.20 ± 0.08 μg/mL) displayed the most potent antibacterial potential against E. coli in comparison to the standard drug penicillin (MIC = 2.4 ± 1.00 μg/mL). Molecular docking studies further helped in an extensive understanding of all of the interactions between compounds and the enzyme active site, and DFT studies were also employed to gain insights into the molecular structure of the synthesized compounds. The results indicated that theophylline-linked triazole derivatives 4b and 4c showed promise as leading contenders in the fight against the HCV virus. Moreover, compounds 4e and 4g demonstrated potential as effective chemotherapeutic agents against E. coli and B. subtilis, respectively. To substantiate these findings, additional in vivo studies and clinical trials are imperative, laying the groundwork for their integration into future drug design and development.

Urease, a nickel-dependent enzyme found in various life forms, catalyzes urea breakdown, concluding nitrogen metabolism by generating ammonia and carbamate. This process causes a rise in pH, supports the survival of pathogens, and can lead to infections such as gastric disorders like ulcers and cancer in humans. Helicobacter pylori employs urease for survival in the acidic environment of the stomach and in protein synthesis. To treat such infections and inhibit the growth of pathogens, it is mandatory to obstruct urease activity; therefore, derivatives of 1-(3-nitropyridin-2-yl)piperazine were synthesized (5a-o; 7a-k). All these newly synthesized compounds were investigated for urease inhibition by in vitro inhibition assays. The results showed that 5b and 7e are the most active inhibitors, having IC50 values of 2.0 ± 0.73 and 2.24 ± 1.63 µM, respectively. These IC50 values are lower than the IC50 value of the standard thiourea, which was 23.2 ± 11.0 µM. The hemolysis potential of 5b, 5c, 5i, 7e, and 7h was also determined; 7e and 7h exhibited good biocompatibility in human blood cells. Through in silico analysis, it was shown that both these potent inhibitors develop favorable interactions with the active site of urease, having binding energies of −8.0 (5b) and −8.1 (7e) kcal/mol. The binding energy of thiourea was −2.8 kcal/mol. Moreover, 5b and 7e have high gastrointestinal permeability as predicted via computational analysis. On the other hand, the IC50 value and binding energy of precursor compound 3 was 3.90 ± 1.91 µM and −6.1 kcal/mol, respectively. Consequently, 5b and 7e can serve as important inhibitors of urease.

Green synthesis using L-proline as an organocatalyst is crucial due to its reusability, mild conditions, clean reactions, easy workup, high purity, short reaction times, and high yields. However, existing methods often involve harsh conditions and longer reaction times. In this study, 2-cyano-N’-(2-cyanoacetyl)acetohydrazide (3) was prepared and condensed with various benzaldehyde derivatives to yield 2-cyano-N’-(2-cyano-3-phenylacryloyl)-3-phenylacrylohydrazide derivatives (5a–e, 7a,b) using a grinding technique with moist L-proline. Additionally, three 2-cyano-N’-(2-cyano-3-heterylbut-2-enoyl)-3-heterylbut-2-enehydrazides (9, 11, 13) were synthesized by condensing compound 3 with respective (heteraryl)ketones (8, 10, 12) following the same method. The synthesized compounds were characterized using IR, NMR, and MS spectroscopy. L-proline’s reusability was confirmed for up to four cycles without significant yield loss, showcasing the protocol’s efficiency and sustainability. The new compounds were screened for anticancer activities against the HCT-116 colon carcinoma cell line using the MTT assay. Molecular docking studies revealed the binding conformations of the most potent compounds to the target protein (PDB ID 6MTU), correlating well with in vitro results. In silico ADMET analysis indicated favorable pharmacokinetic properties, highlighting these novel compounds as promising targeted anti-colon cancer agents.

According to the World Health Organization, over 422 million people worldwide have diabetes, with the majority residing in low- and middle-income countries. Diabetes causes 1.5 million fatalities a year. The number of diabetes cases and its prevalence have progressively increased over the last few decades. This study aims to determine the phytochemicals in the edible part of Perkia javanica, predict their α-glucosidase inhibitory potential, one of the promising targets for diabetes, and then carry out in vitro and in vivo studies. The phytochemicals present in the n-butanol fraction of the methanol extract of P. javanica pods were analyzed using UHPLC-QTOF-MS/MS (Ultra-High-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry). The UHPLC-QTOF analysis revealed the presence of 79 different compounds in the n-butanol fraction. Among these, six compounds demonstrated excellent binding affinities with α-glucosidase, surpassing the performance of two standard inhibitors, Miglitol and Voglibose. In vitro α-glucosidase inhibitory activities were assessed by the n-butanol fraction, followed by in vivo studies. According to the in vitro study, the inhibitory efficiency against α-glucosidase was determined to have an IC50 value of 261.9 µg/mL. The in vivo findings revealed a significant reduction in blood glucose levels in Swiss albino mice treated with the same extract, decreasing from 462.66 mg/dL to 228.66 mg/dL. Additionally, the extract significantly increased the activity of the enzymes catalase and superoxide dismutase (SOD) and decreased the amount of malondialdehyde (MDA) in the liver and kidney tissue. The predicted physicochemical parameters indicated that most of the compounds would be excreted from the body after inhibition in the small intestine without being absorbed. Considering the low cost and wide availability of raw materials, P. javanica pods can serve as a good food supplement that may help prevent type 2 diabetes management.

Abstract Prunus armeniaca gum is used as food additive and ethno medicinal purpose. Two empirical models response surface methodology and artificial neural network were used to search for optimized extraction parameters for gum extraction. A four-factor design was implemented for optimization of extraction process for maximum yield which was obtained under the optimized extraction parameter (temperature, pH, extraction time, and gum/water ratio). Micro and macro-elemental composition of gum was determined by using laser induced breakdown spectroscopy. Gum was evaluated for toxicological effect and pharmacological properties. The maximum predicted yield obtained by response surface methodology and artificial neural network was 30.44 and 30.70% which was very close to maximum experimental yield 30.23%. Laser induced breakdown spectroscopic spectra confirmed the presence Calcium, Potassium, Magnesium, Sodium, Lithium, Carbon, Hydrogen, Nitrogen and Oxygen. Acute oral toxicity study showed that gum is non-toxic up to 2000 mg/Kg body weight in rabbits, accompanied by high cytotoxic effects of gum against HepG2 and MCF-7cells by MTT assay. Overall, Aqueous solution of gum showed various pharmacological activities with significant value of antioxidant, antibacterial, anti-nociceptive, anti-cancer, anti-inflammatory and thrombolytic activities. Thus, optimization of parameters using mathematical models cans offer better prediction and estimations with enhanced pharmacological properties of extracted components.

CB2R are fascinating targets for neuropathic pain and mood disorders because of their improved biological characteristics. Experimental data on 1296 cannabinoid-2 receptor inhibitors with different structural properties were used to develop a QSAR model following OECD guidelines. This study selected the best-predicted model (80:20 splitting ratio) with fitting parameters, such as R2:0.78; F:623.6, Internal validation parameters, such as Q2Loo:0.78; CCCcv: 0.87 and external validation parameters, such as R2ext:0.77; Q2F1:0.7730; Q2F2:0.7730; Q2F3:0.76; CCCext:0.87. Following this, another QSAR model was developed by using a 50:50 split ratio for thetraining and the prediction sets, which were then swapped to evaluate the robustness of the built QSAR model by the 50:50 ratio, which also gives a deeper understanding of the chemical space. In addition, we have confirmed the QSAR result with pharmacophore modelling, and supported by molecular docking, MD simulation, MMGBSA and ADME studies. Thus, this work may enable cannabinoid 2 receptor inhibsitor development.

A growing interest in pharmacology has made heterocyclic chemistry as one of the emerging branches of organic chemistry. Piperazine is an excellent heterocycle that possesses a large span of pharmaceutical applications. Piperazine derived compounds have shown multiple therapeutic activities such as antioxidant, antibacterial, analgesic, anticancer, antihypertensive, antiallergic, anti-inflammatory, antimalarial, antipsychotic, cardioprotective, antifungal, antidepressant and antiviral. FDA has approved many piperazine scaffold-based drugs for the treatment of various viral infections, therefore establishing the pharmacological importance of piperazine derivatives. Only a few reviews on antiviral activities of piperazine containing compounds are available in the literature, despite of its great medicinal significance. This review deals with piperazine derived compounds as antiviral agents covering the literature reports from 2010 to 2023.

Biomaterials are widely used for various medical purposes, for instance, implants, tissue engineering, medical devices, and drug delivery systems. Natural biomaterials can be obtained from proteins, carbohydrates, and cell-specific sources. However, when these biomaterials are introduced into the body, they trigger an immune response which may lead to rejection and failure of the implanted device or tissue. The immune system recognizes natural biomaterials as foreign substances and triggers the activation of several immune cells, for instance, macrophages, dendritic cells, and T cells. These cells release pro-inflammatory cytokines and chemokines, which recruit other immune cells to the implantation site. The activation of the immune system can lead to an inflammatory response, which can be beneficial or detrimental, depending on the type of natural biomaterial and the extent of the immune response. These biomaterials can also influence the immune response by modulating the behavior of immune cells. For example, biomaterials with specific surface properties, such as charge and hydrophobicity, can affect the activation and differentiation of immune cells. Additionally, biomaterials can be engineered to release immunomodulatory factors, such as anti-inflammatory cytokines, to promote a tolerogenic immune response. In conclusion, the interaction between biomaterials and the body’s immune system is an intricate procedure with potential consequences for the effectiveness of therapeutics and medical devices. A better understanding of this interplay can help to design biomaterials that promote favorable immune responses and minimize adverse reactions.

Water contamination can be detrimental to the human health due to higher concentration of carcinogenic heavy metals such as chromium (Cr) in the wastewater. Many traditional methods are being employed in wastewater treatment plants for Cr removal to control the environmental impacts. Such methods include ion exchange, coagulation, membrane filtration, and chemical precipitation and microbial degradation. Recent advances in materials science and green chemistry have led to the development of nanomaterial that possess high specific surface areas and multiple functions, making them suitable for removing metals such as Cr from wastewater. Literature shows that the most efficient, effective, clean, and long-lasting approach for removing heavy metals from wastewater involves adsorbing heavy metals onto the surface of nanomaterial. This review assesses the removal methods of Cr from wastewater, advantages and disadvantages of using nanomaterial to remove Cr from wastewater and potential negative impacts on human health. The latest trends and developments in Cr removal strategies using nanomaterial adsorption are also explored in the present review.

Imidazothiadiazole is a fundamental fused heterocyclic compound containing imidazole and thiadiazole ring systems. This versatile framework has significant applications in pharmaceutical chemistry and also possessed a remarkable biological profile. The derivatives of imidazo[2,1-b][1,3,4]thiadiazole have a broad spectrum of biological applications such as antitumor, tubulin inhibitor, anticancer, antifungal, anti-inflammatory, antimicrobial, antitubercular, anticonvulsant, antibacterial and as enzyme inhibitors. These derivatives also play a significant role in the development of non-linear optics and photo-electronics. Synthesis of this fused bicyclic compound mainly involved the reaction between 2-amino-1,3,4-thiadiazoles and α-haloketones, with different substitutions at the 2, 5, and 6 positions of the ring system. Moreover, microwave assisted multicomponent and C–C coupling reactions in the presence of catalysts or under solvent free reaction conditions were found to be reliable and valuable approaches. This review is a concerted approach to describe the synthesis and applications of imidazo[2,1-b][1,3,4] thiadiazole derivatives reported during 2015–2022.

Mosquitoes are the primary vector for West Nile virus, a flavivirus. The virus’s ability to infiltrate and establish itself in increasing numbers of nations has made it a persistent threat to public health worldwide. Despite the widespread occurrence of this potentially fatal disease, no effective treatment options are currently on the market. As a result, there is an immediate need for the research and development of novel pharmaceuticals. To begin, molecular docking was performed on two possible West Nile virus target proteins using a panel of twelve natural chemicals, including Apigenin, Resveratrol, Hesperetin, Fungisterol, Lucidone, Ganoderic acid, Curcumin, Kaempferol, Cholic acid, Chlorogenic acid, Pinocembrin, and Sanguinarine. West Nile virus methyltransferase (PDB ID: 2OY0) binding affinities varied from −7.4 to −8.3 kcal/mol, whereas West Nile virus envelope glycoprotein affinities ranged from −6.2 to −8.1 kcal/mol (PDB ID: 2I69). Second, substances with larger molecular weights are less likely to be unhappy with the Lipinski rule. Hence, additional research was carried out without regard to molecular weight. In addition, compounds 01, 02, 03, 05, 06, 07, 08, 09, 10 and 11 are more soluble in water than compound 04 is. Besides, based on maximum binding affinity, best three compounds (Apigenin, Curcumin, and Ganoderic Acid) has been carried out molecular dynamic simulation (MDs) at 100 ns to determine their stability. The MDs data is also reported that these mentioned molecules are highly stable. Finally, advanced principal component analysis (PCA), dynamics cross-correlation matrices (DCCM) analysis, binding free energy and dynamic cross correlation matrix (DCCM) theoretical study is also included to established mentioned phytochemical as a potential drug candidate. Research has indicated that the aforementioned natural substances may be an effective tool in the battle against the dangerous West Nile virus. This study aims to locate a bioactive natural component that might be used as a pharmaceutical.

IntroductionNeurodegeneration and cancer present in comorbidities with inverse effects due to the expression of genes and pathways acting in opposition. Identifying and studying the genes simultaneously up or downregulated during morbidities helps curb both ailments together.MethodsThis study examines four genes. Three of these (Amyloid Beta Precursor Protein (APP), Cyclin D1 (CCND1), and Cyclin E2 (CCNE2) are upregulated, and one protein phosphatase 2 phosphatase activator (PTPA) is simultaneously downregulated in both disorders. We investigated molecular patterns, codon usage, codon usage bias, nucleotide bias in the third codon position, preferred codons, preferred codon pairs, rare codons, and codon context.ResultsParity analysis revealed that T is preferred over A, and G is preferred over C in the third codon position, suggesting composition plays no role in nucleotide bias in both the upregulated and downregulated gene sets and that mutational forces are stronger in upregulated gene sets than in downregulated ones. Transcript length influenced the overall %A composition and codon bias, and the codon AGG exerted the strongest influence on codon usage in both the upregulated and downregulated gene sets. Codons ending in G/C were preferred for 16 amino acids, and glutamic acid-, aspartic acid-, leucine-, valine-, and phenylalanine-initiated codon pairs were preferred in all genes. Codons CTA (Leu), GTA (Val), CAA (Gln), and CGT (Arg) were underrepresented in all examined genes.DiscussionUsing advanced gene editing tools such as CRISPR/Cas or any other gene augmentation technique, these recoded genes may be introduced into the human body to optimize gene expression levels to augment neurodegeneration and cancer therapeutic regimens simultaneously.

Water contamination with synthetic dyes is an escalating problem worldwide. Herein, Co3O4-decorated reduced graphene oxide (Co3O4-rGO) is reported as an effective heterogeneous photocatalyst for the decomposition of organic dyes. The synthesis of Co3O4-rGO was confirmed via spectroscopic techniques including XRD, XPS, TEM, and FTIR. After characterization, the prepared Co3O4-rGO composite was tested as a photocatalyst for the degradation of methylene blue and methyl orange. The photocatalytic efficiency of Co3O4-rGO was >95% after 60 min, corresponding to 200 mg/L as the initial concentration of each dye. The photodegradation of MB and MO was confirmed by BOD and COD measurements. Experimental parameters like the re-usability of Co3O4-rGO, the effect of catalyst dosage, and the effect of dye concentration on photocatalytic activity were also investigated. The photocatalytic activity of Co3O4-rGO for the degradation of MB was 2.13 and 3.43 times higher than that of Co3O4 and rGO, respectively. Similarly, the photocatalytic activity of Co3O4-rGO for the degradation of MO was 2.36 and 3.56 times higher than that of Co3O4 and rGO, respectively. Hence, Co3O4-rGO was found to be an efficient and reusable photocatalyst for the decomposition of selected dyes in the aqueous medium.

Rudolf Virchow was the first person to point out the important link between immune function and cancer. He did this by noticing that leukocytes were often found in tumors. Overexpression of arginase 1 (ARG1) and inducible nitric oxide synthase (iNOS) in myeloid-derived suppressor cells (MDSCs) and tumour-associated macrophages (TAMs) depletes both intracellular and extracellular arginine. TCR signalling is slowed as a result, and the same types of cells produce reactive oxygen and nitrogen species (ROS and RNS), which aggravates the situation. Human arginase I is a double-stranded manganese metalloenzyme that helps L-arginine break down into L-ornithine and urea. Thus, a quantitative structure-activity relationship (QSAR) analysis was performed to unearth the unrecognised structural aspects crucial for arginase-I inhibition. In this work, a balanced QSAR model with good prediction performance and clear mechanistic interpretation was developed using a dataset of 149 molecules encompassing a broad range of structural scaffolds and compositions. The model was made to meet OECD standards, and all of its validation parameters have values that are higher than the minimum requirements (R2tr = 0.89, Q2LMO = 0.86, and R2ex = 0.85). The present QSAR study linked structural factors to arginase-I inhibitory action, including the proximity of lipophilic atoms to the molecule’s centre of mass (within 3A), the position of the donor to the ring nitrogen (exactly 3 bonds away), and the surface area ratio. As OAT-1746 and two others are the only arginase-I inhibitors in development at the time, we have performed a QSAR-based virtual screening with 1650 FDA compounds taken from the zinc database. In this screening, 112 potential hit compounds were found to have a PIC50 value of less than 10 nm against the arginase-I receptor. The created QSAR model’s application domain was evaluated in relation to the most active hit molecules identified using QSAR-based virtual screening, utilising a training set of 149 compounds and a prediction set of 112 hit molecules. As shown in the Williams plot, the top hit molecule, ZINC000252286875, has a low leverage value of HAT i/i h* = 0.140, placing it towards the boundary of the usable range. Furthermore, one of 112 hit molecules with a docking score of −10.891 kcal/mol (PIC50 = 10.023 M) was isolated from a study of arginase-I using molecular docking. Protonated ZINC000252286875-linked arginase-1 showed 2.9 RMSD, whereas non-protonated had 1.8. RMSD plots illustrate protein stability in protonated and non-protonated ZINC000252286875-bound states. Protonated-ZINC000252286875-bound proteins contain 25 Rg. The non-protonated protein-ligand combination exhibits a 25.2-Rg, indicating compactness. Protonated and non-protonated ZINC000252286875 stabilised protein targets in binding cavities posthumously. Significant root mean square fluctuations (RMSF) were seen in the arginase-1 protein at a small number of residues for a time function of 500 ns in both the protonated and unprotonated states. Protonated and non-protonated ligands interacted with proteins throughout the simulation. ZINC000252286875 bound Lys64, Asp124, Ala171, Arg222, Asp232, and Gly250. Aspartic acid residue 232 exhibited 200% ionic contact. 500-ns simulations-maintained ions. Salt bridges for ZINC000252286875 aided docking. ZINC000252286875 created six ionic bonds with Lys68, Asp117, His126, Ala171, Lys224, and Asp232 residues. Asp117, His126, and Lys224 showed 200% ionic interactions. In protonated and deprotonated states, GbindvdW, GbindLipo, and GbindCoulomb energies played crucial role. Moreover, ZINC000252286875 meets all of the ADMET standards to serve as a drug. As a result, the current analyses were successful in locating a novel and potent hit molecule that inhibits arginase-I effectively at nanomolar concentrations. The results of this investigation can be used to develop brand-new arginase I inhibitors as an alternative immune-modulating cancer therapy.

IntroductionAntibacterial drug resistance, brought on by the overuse of antibiotics, is one of the biggest threats to human health. It is crucial to consider cutting-edge strategies, such as herbal remedies, to control multidrug-resistant (MDR) bacteria.MethodsThis study evaluated the phytochemical, antioxidant and antibacterial properties of the various Tinospora cordifolia extracts. Functionalization of the isolated active compound was done using gold (Au) and silver (Ag) nanoparticles (NPs). Further, to understand the interaction of the isolated class, Cordifolisides, with its target, various in-silico methods were used.Results and DiscussionThe plant was reported from the Charaideo district of Assam, whose methanolic stem extract showed the maximum activity towards the nosocomial pathogen Pseudomonas aeruginosa. Consequently, the active compound was isolated and characterized as belonging to the class Cordifoliside using NMR. The AuNPs and AgNPs functionalized isolates showed enhanced antimicrobial activity against P. aeruginosa compared to the unfunctionalized isolate. The most reactive compound, Cordifoliside C was determined using Density Functional Theory (DFT) analysis, whose interactions with the TolB protein were studied using molecular docking methods, which revealed good binding interactions of Cordifoliside C with the TolB protein.ConclusionThis study offers enormous potential for drug design and might be used as a pipeline to address the urgent problem of multidrug-resistance in bacteria. Graphical Abstract

This study reports the interfacial phenomenon of cefotaxime in combination with nonionic surfactants, Triton X-100 (TX-100) and Tween-80 (TW-80), and their mixed micellar formulations. Cefotaxime was enclosed in a micellar system to improve its solubility and effectiveness. TX-100 and TW-80 were used in an amphiphilic self-assembly process to create the micellar formulation. The effect of the addition of TX-100, a nonionic surfactant, on the ability of TW-80 to solubilize the drug was examined. The values of the critical micelle concentration (CMC) were determined via UV-Visible spectroscopy. Gibbs free energies (ΔGp and ΔGb), the partition coefficient (Kx), and the binding constant (Kb) were also computed. In a single micellar system, the partition coefficient (Kx) was found to be 33.78 × 106 and 2.78 × 106 in the presence of TX-100 and TW-80, respectively. In a mixed micellar system, the value of the partition coefficient for the CEF/TW-80 system is maximum (5.48 × 106) in the presence of 0.0019 mM of TX-100, which shows that TX-100 significantly enhances the solubilizing power of micelles. It has been demonstrated that these surfactants are effective in enhancing the solubility and bioavailability of therapeutic compounds. This study elaborates on the physicochemical characteristics and solubilization of reactive drugs in single and mixed micellar media. This investigation, conducted in the presence of surfactants, shows a large contribution to the binding process via both hydrogen bonding and hydrophobic interactions.

Molecular hybridization has emerged as the prime and most significant approach for the development of novel anticancer chemotherapeutic agents for combating cancer. In this pursuit, a novel series of indole–1,2,4-triazol-based N-phenyl acetamide structural motifs 8a–f were synthesized and screened against the in vitro hepatocellular cancer Hep-G2 cell line. The MTT assay was applied to determine the anti-proliferative potential of novel indole–triazole compounds 8a–f, which displayed cytotoxicity potential as cell viabilities at 100 µg/mL concentration, by using ellipticine and doxorubicin as standard reference drugs. The remarkable prominent bioactive structural hybrids 8a, 8c, and 8f demonstrated good-to-excellent anti-Hep-G2 cancer chemotherapeutic potential, with a cell viability of (11.72 ± 0.53), (18.92 ± 1.48), and (12.93 ± 0.55), respectively. The excellent cytotoxicity efficacy against the liver cancer cell line Hep-G2 was displayed by the 3,4-dichloro moiety containing indole–triazole scaffold 8b, which had the lowest cell viability (10.99 ± 0.59) compared with the standard drug ellipticine (cell viability = 11.5 ± 0.55) but displayed comparable potency in comparison with the standard drug doxorubicin (cell viability = 10.8 ± 0.41). The structure–activity relationship (SAR) of indole–triazoles 8a–f revealed that the 3,4-dichlorophenyl-based indole–triazole structural hybrid 8b displayed excellent anti-Hep-G2 cancer chemotherapeutic efficacy. The in silico approaches such as molecular docking scores, molecular dynamic simulation stability data, DFT, ADMET studies, and in vitro pharmacological profile clearly indicated that indole–triazole scaffold 8b could be the lead anti-Hep-G2 liver cancer therapeutic agent and a promising anti-Hep-G2 drug candidate for further clinical evaluations.

Benzofuran, 1,3,4-oxadiazole, and 1,2,4-triazole are privileged heterocyclic moieties that display the most promising and wide spectrum of biological activities against a wide variety of diseases. In the current study, benzofuran-1,3,4-oxadiazole BF1–BF7 and benzofuran-1,2,4-triazole compounds BF8–BF15 were tested against HCV NS5B RNA-dependent RNA polymerase (RdRp) utilizing structure-based screening via a computer-aided drug design (CADD) approach. A molecular docking approach was applied to evaluate the binding potential of benzofuran-appended 1,3,4-oxadiazole and 1,2,4-triazole BF1–BF15 molecules. Benzofuran-1,3,4-oxadiazole scaffolds BF1–BF7 showed lesser binding affinities (−12.63 to −14.04 Kcal/mol) than benzofuran-1,2,4-triazole scaffolds BF8–BF15 (−14.11 to −16.09 Kcal/mol) against the HCV NS5B enzyme. Molecular docking studies revealed the excellent binding affinity scores exhibited by benzofuran-1,2,4-triazole structural motifs BF-9 (−16.09 Kcal/mol), BF-12 (−15.75 Kcal/mol), and BF-13 (−15.82 Kcal/mol), respectively, which were comparatively better than benzofuran-based HCV NS5B inhibitors’ standard reference drug Nesbuvir (−15.42 Kcal/mol). A molecular dynamics simulation assay was also conducted to obtain valuable insights about the enzyme–compounds interaction profile and structural stability, which indicated the strong intermolecular energies of the BF-9+NS5B complex and the BF-12+NS5B complex as per the MM-PBSA method, while the BF-12+NS5B complex was the most stable system as per the MM-GBSA calculation. The drug-likeness and ADMET studies of all the benzofuran-1,2,4-triazole derivatives BF8–BF15 revealed that these compounds possessed good medicinal chemistry profiles in agreement with all the evaluated parameters for being drugs. The molecular docking affinity scores, MM-PBSA/MM-GBSA and MD-simulation stability analysis, drug-likeness profiling, and ADMET study assessment indicated that N-4-fluorophenyl-S-linked benzofuran-1,2,4-triazole BF-12 could be a future promising anti-HCV NS5B RdRp inhibitor therapeutic drug candidate that has a structural agreement with the Nesbuvir standard reference drug.

The ongoing COVID-19 pandemic has resulted in a global panic because of its continual evolution and recurring spikes. This serious malignancy is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the outbreak, millions of people have been affected from December 2019 till now, which has led to a great surge in finding treatments. Despite trying to handle the pandemic with the repurposing of some drugs, such as chloroquine, hydroxychloroquine, remdesivir, lopinavir, ivermectin, etc., against COVID-19, the SARS-CoV-2 virus continues its out-of-control spread. There is a dire need to identify a new regimen of natural products to combat the deadly viral disease. This article deals with the literature reports to date of natural products showing inhibitory activity towards SARS-CoV-2 through different approaches, such as in vivo, in vitro, and in silico studies. Natural compounds targeting the proteins of SARS-CoV-2—the main protease (Mpro), papain-like protease (PLpro), spike proteins, RNA-dependent RNA polymerase (RdRp), endoribonuclease, exoribonuclease, helicase, nucleocapsid, methyltransferase, adeno diphosphate (ADP) phosphatase, other nonstructural proteins, and envelope proteins—were extracted mainly from plants, and some were isolated from bacteria, algae, fungi, and a few marine organisms.

Benzofuran and 1,3,4-oxadiazole are privileged and versatile heterocyclic pharmacophores which display a broad spectrum of biological and pharmacological therapeutic potential against a wide variety of diseases. This article reports in silico CADD (computer-aided drug design) and molecular hybridization approaches for the evaluation of the chemotherapeutic efficacy of 16 S-linked N-phenyl acetamide moiety containing benzofuran-1,3,4-oxadiazole scaffolds BF1–BF16. This virtual screening was carried out to discover and assess the chemotherapeutic efficacy of BF1–BF16 structural motifs as Mycobacterium tuberculosis polyketide synthase 13 (Mtb Pks13) enzyme inhibitors. The CADD study results revealed that the benzofuran clubbed oxadiazole derivatives BF3, BF4, and BF8 showed excellent and remarkably significant binding energies against the Mtb Pks13 enzyme comparable with the standard benzofuran-based TAM-16 inhibitor. The best binding affinity scores were displayed by 1,3,4-oxadiazoles-based benzofuran scaffolds BF3 (−14.23 kcal/mol), BF4 (−14.82 kcal/mol), and BF8 (−14.11 kcal/mol), in comparison to the binding affinity score of the standard reference TAM-16 drug (−14.61 kcal/mol). 2,5-Dimethoxy moiety-based bromobenzofuran-oxadiazole derivative BF4 demonstrated the highest binding affinity score amongst the screened compounds, and was higher than the reference Pks13 inhibitor TAM-16 drug. The bindings of these three leads BF3, BF4, and BF8 were further confirmed by the MM-PBSA investigations in which they also exhibited strong bindings with the Pks13 of Mtb. Moreover, the stability analysis of these benzofuran-1,3,4-oxadiazoles in the active sites of the Pks13 enzyme was achieved through molecular dynamic (MD) simulations at 250 ns virtual simulation time, which indicated that these three in silico predicted bio-potent benzofuran tethered oxadiazole molecules BF3, BF4, and BF8 demonstrated stability with the active site of the Pks13 enzyme.

Alzheimer’s disease (AD) is a severe neurodegenerative disorder of the brain that manifests as dementia, disorientation, difficulty in speech, and progressive cognitive and behavioral impairment. The emerging therapeutic approach to AD management is the inhibition of β-site APP cleaving enzyme-1 (BACE1), known to be one of the two aspartyl proteases that cleave β-amyloid precursor protein (APP). Studies confirmed the association of high BACE1 activity with the proficiency in the formation of β-amyloid-containing neurotic plaques, the characteristics of AD. Only a few FDA-approved BACE1 inhibitors are available in the market, but their adverse off-target effects limit their usage. In this paper, we have used both ligand-based and target-based approaches for drug design. The QSAR study entails creating a multivariate GA-MLR (Genetic Algorithm-Multilinear Regression) model using 552 molecules with acceptable statistical performance (R2 = 0.82, Q2loo = 0.81). According to the QSAR study, the activity has a strong link with various atoms such as aromatic carbons and ring Sulfur, acceptor atoms, sp2-hybridized oxygen, etc. Following that, a database of 26,467 food compounds was primarily used for QSAR-based virtual screening accompanied by the application of the Lipinski rule of five; the elimination of duplicates, salts, and metal derivatives resulted in a truncated dataset of 8,453 molecules. The molecular descriptor was calculated and a well-validated 6-parametric version of the QSAR model was used to predict the bioactivity of the 8,453 food compounds. Following this, the food compounds whose predicted activity (pKi) was observed above 7.0 M were further docked into the BACE1 receptor which gave rise to the Identification of 4-(3,4-Dihydroxyphenyl)-2-hydroxy-1H-phenalen-1-one (PubChem I.D: 4468; Food I.D: FDB017657) as a hit molecule (Binding Affinity = −8.9 kcal/mol, pKi = 7.97 nM, Ki = 10.715 M). Furthermore, molecular dynamics simulation for 150 ns and molecular mechanics generalized born and surface area (MMGBSA) study aided in identifying structural motifs involved in interactions with the BACE1 enzyme. Molecular docking and QSAR yielded complementary and congruent results. The validated analyses can be used to improve a drug/lead candidate’s inhibitory efficacy against the BACE1. Thus, our approach is expected to widen the field of study of repurposing nutraceuticals into neuroprotective as well as anti-cancer and anti-viral therapeutic interventions.