Alzheimer's disease (AD) remains a devastating neurodegenerative disorder with no disease-modifying therapies available, largely due to its complex, multifactorial pathophysiology involving amyloid β (Aβ) aggregation, tau hyperphosphorylation, chronic neuroinflammation, oxidative stress, and proteasomal dysfunction. This review comprehensively evaluates the synthesis and biological evaluation of pyrazole derivatives as promising multi-target-directed ligands (MTDLs) for Alzheimer's therapy. The pyrazole scaffold, with its exceptional structural versatility and ease of synthetic modification, has enabled the rational design of diverse compound classes targeting multiple AD-relevant pathways simultaneously. Diphenylpyrazoles function as non-competitive β-secretase (BACE1) modulators, selectively suppressing Aβ production while preserving essential physiological enzyme activity, with the lead compound Anle138b demonstrating remarkable ability to block Aβ pore activity, restore synaptic function, and improve memory in transgenic AD mouse models. Arylpyrazolones (exemplified by compound 1, EC₅₀ = 270 nM) exhibit potent anti-amyloidogenic activity with excellent blood-brain barrier permeation and favorable oral bioavailability. Ferrocene-pyrazole-curcumin analogues show structure-dependent anti-amyloidogenic activity validated by thioflavin T fluorescence and atomic force microscopy, combining natural product inspiration with organometallic fine-tuning. Regarding tau pathology, acylaminopyrazoles inhibit glycogen synthase kinase-3β (GSK-3β) in the low micromolarrange, preventing tau hyperphosphorylation and neurofibrillary tangle formation, while pyrazolones enhance ubiquitin-proteasome system activity, promoting clearance of misfolded proteins and protecting neurons from amyloid-induced toxicity. The collective evidence positions pyrazole-based MTDLs as a chemically feasible, pharmacologically versatile platform for addressing the intricate crosstalk among amyloid pathology, tauopathy, neuroinflammation, and proteostasis failure in Alzheimer's disease, offering genuine hope for next-generation disease-modifying therapeutics.

This study presents a comprehensive in silico investigations of five benzimidazole-triazole hybrids (BPHT), checking their activity as Glucosamine-6-phosphate synthase inhibitors by means of molecular docking, ADMET assessment and normal mode studies. BPHT-3 showed the most beneficial docking score (-8.5), suggesting its binding affinity is strong. Based on ADMET screening, BPHT-3 shows good intestinal absorption, little risk to the heart and does not strongly affect certain liver enzymes. Data from normal mode analysis validated that despite being a bendable compound, BPHT-3 remains stable in interactions with the target enzyme since it obtained a very low eigen-value when connected to the target enzyme. In comparison to other derivatives, BPHT-3 gives the most balanced results for binding strength, how the drug gets into the body and flexibility in structure. With this approach, BPHT-3 is identified as a lead compound and researchers should now optimize it and perform experiments based on the importance of combining structural docking, pharmacokinetic modeling and molecular dynamics in early drug discovery.

Benzimidazole shows certain advantages over Benzothiazole, whether in terms of stronger DNA binding, higher anti-cancer efficacy, or broader therapeutic applications. This study assesses the stability of BNZ-AC, based on Benzimidazole moiety conjugated to polyA15polyT15-DNA system in comparison to three other DNA-conjugated systems. Among all four systems, the conjugated DNA with BNZ-AC demonstrated the most favourable interaction, as indicated by a notable thermal stability increase of 6.54 & ring;C and the Gibbs free energy of-19.75 kcal/mol, making it the most stable ligand, surpassing BTZ-AC, and DMBTZ-AC, based on Benzothiazole in terms of binding affinity. Molecular dynamics simulations further supported BNZ-AC's enhanced stability through consistent hydrogen bonding patterns. Moreover, cytotoxicity assays revealed that BNZ-AC exhibited potent activity against Hela cells with a low IC50 of 8.012 mu M, although it was less effective against A549 cells, showing an IC50 of 69.5 mu M. These results indicate that BNZ-AC holds promise as a therapeutic candidate due to its strong DNA binding, superior stability, and significant cytotoxic activity against cancer cells, thus Benzimidazoles edges over Benzothiazole analogues.

Molecular Modelling in Drug Designing or Computer Aided Drug Designing (CADD) plays a significant role in new drug identification in the current world. However, it has sensitivity challenges and limitation because theoretical models involve assumption and approximations Computational models are not very accurate, some of the major challenges that face these models include the following. These include, for instance, molecular-docking or molecular-dynamics-simulation models which may not represent an accurate biological system and thus the predictions will be wrong. CADD depends on the availability of accurate, high-quality structural information for target proteins and ligand. Unfortunately, there are instances when experimental structures are not available, and homology models are employed, which can be imprecise. The computational cost is another drawback; only high accuracy simulations call for huge amounts of computational power and time well-suited for screening a multitude of agents. Moreover, they have weaknesses in determining pharmacokinetic and toxicity patterns of compounds that influence drug performance and effectiveness. In other words, even though CADD greatly helps drug discovery, it is still constrained by experimental validation to solve its drawbacks and optimize its foretelling.

The optimization of pharmacokinetic properties is vital in drug development, necessitating comprehensive metabolism studies to predict effective therapeutic doses. In contemporary research, in silico and mechanistic approaches are increasingly employed to design molecules and anticipate their metabolic pathways. This study focuses on the investigation of potential sites of metabolism (SOMs) of new indole-quinoline derivatives and colchicine. In silico methodologies were used to identify the potential SOMs for both compounds, corroborating our findings through docking studies against various cytochrome P450 (CYP) isoforms. The results were further validated through molecular docking studies using AutoDock, followed by molecular simulations conducted with Internal coordinates normal mode analysis server (iMOD). Biotransformer 3.0, suggested 13 possible metabolites for colchicine mainly due to O-dealkylation mediated by CYP1A2 and CYP2C9 while 12 metabolites resulted from the indole-quinoline derivative mainly by hydroxylation and O-dealkylation reactions facilitated by CYP1A2, CYP2C9 and CYP3A4 enzymes. Docking studies concluded that both compounds have better affinity towards CYP1A2 and CYP2C9 than standard. The results suggest how colchicine and indole-quinoline derivatives are metabolized and stress the need of CYP enzyme interactions for these pathways. The results of our biotransformation computation study pointing toward understanding the metabolic pattern of colchicine and indole-quinoline derivative and future directions include experimental validation of predicted metabolites using in vitro or in vivo systems. These insights can be integrated into absorption, distribution, metabolism, excretion, and toxicity profiling to optimize drug-like properties and minimize potential toxicity.

Substituted benzo[h]quinolines have been regarded as potential biophores in biologically related investigations based on their selective interactions with DNA. Sustained and complex interactions of this nature further make benzo[h]quinoline derivatives quite appealing to anticancer and antimicrobial activities. Because the studied compounds act on cells that are rapidly dividing, they can provoke apoptosis or cell cycle arrest, or other positive effects. Furthermore, they are chemically diverse, which makes it possible to design and produce products with selective activity and fewer side effects. However, some difficulties are valid for them, concerning the improvement of pharmacokinetic profiles and the reduction of toxicity. Because of chemical diversity, it is possible to create benzo[h] quinoline‐based molecules that choose certain actions and cause fewer side effects. The docking study shows that the quinoline core can be optimized by adding an electronegative group, such as a sulfonic acid and halogens, to increase hydrogen bonding and appropriate alignment within the DNA binding groove. These alkylation results parallel the studies for targeting DNA with quinoline derivatives for cancer and antibiotic applications in the future. Furthermore, more detailed in vitro, along in vivo experiments are necessary to authenticate predictive aptitude and distinguish biological efficacy. Among these six derivatives, 4‐chloroquinoline and 2‐dihydro‐methoxyquinoline were identified as favorable leads, while quinoline‐6‐sulfonic acid was flagged as safer. In the future, researchers should pay specific attention to enhancing polarity and minimizing toxicity due to its applicability in clinical situations.

This study introduces a versatile method for coupling single-stranded DNA with small heterocyclic compounds, leveraging the reactivity of amino and carboxylic functional groups. By employing COMU and Collidine, BNIMZ and BNTZA were successfully coupled with poly-T DNA. The conjugation technique was successfully confirmed by high accuracy MALDI-TOF MS. This approach offers a reliable and efficient strategy for constructing DNA-conjugates with tailored properties.

The most common primary intraocular childhood cancer that affects children’s and adults’ vision worldwide is retinoblastoma. It is uveal melanoma when contrasting and contrasting with adults. It is a lethal tumor that has the potential to enlarge and destroy the eye and the structures that surround it. As a result, early detection of retinoblastoma in young children is essential. The research's primary impact is the identification of retinal tumor cells. It's also important to determine the tumor's stages and group. Ophthalmologists can better predict and diagnose retinoblastoma cancer at an earlier stage based on the proposed systems. Utilizing machine learning techniques, this study proposes a novel technique for detecting retinoblastoma tumors utilizing radioactive polymeric material in Nanostructure analysis with ion beam based raman spectroscopy. The region of the tumor is examined using raman spectroscopy, and its characteristics are then extracted and categorized. Convolutional Principal kernel networks are used for the tumor feature extraction, and an ensemble of multilayer Q-regressive back propagation networks is used for the classification. For various retinoblastoma datasets, the experimental analysis is conducted in terms of training accuracy, RMSE, F_measure, recall, and AUC. The proposed technique attained training accuracy of 95%, RMSE of 55%, F_measure of 65%, recall of 58%, AUC of 49%.

Well known benzimidazole based drugs – astemizole, omeprazole, lansoprazole, and thiabendazole – are studied whether those can bind with two different oligonucleotides sequences or not. Molecular docking study and further molecular dynamics are employed to find out the capability of these drugs toward different DNA sequences. The substitution at N2 with different atoms/group or heterocyclic moieties favors the binding in the major groove of DNA in most of the cases. The substitutions at N1 beside N2 position clearly increase the binding possibility of astemizole as compared to the rest. Various functional possibilities of known drugs through DNA recognitions may be explored in drug repurposing purposes in virtue of present study.

Coronavirus disease-2019 (COVID-19) has become a global pandemic, necessitating the development of new medicines. In this investigation, we identified potential natural flavonoids and compared their inhibitory activity against spike glycoprotein, which is a target of SARS-CoV-2 and SARS-CoV. The target site for the interaction of new inhibitors for the treatment of SARS-CoV-2 has 82% sequence identity and the remaining 18% dissimilarities in RBD S1-subunit, S2-subunit, and 2.5% others. Molecular docking was employed to analyse the various binding processes used by each ligand in a library of 85 natural flavonoids that act as anti-viral medications and FDA authorised treatments for COVID-19. In the binding pocket of the target active site, remdesivir has less binding interaction than pectolinarin, according to the docking analysis. Pectolinarin is a natural flavonoid isolated from Cirsiumsetidensas that has anti-cancer, vasorelaxant, anti-inflammatory, hepatoprotective, anti-diabetic, anti-microbial, and anti-oxidant properties. The S-glycoprotein RBD region (330–583) is inhibited by kaempferol, rhoifolin, and herbacetin, but the S2 subunit (686–1270) is inhibited by pectolinarin, morin, and remdesivir. MD simulation analysis of S-glycoprotein of SARS-CoV-2 with pectolinarin complex at 100ns based on high dock-score. Finally, ADMET analysis was used to validate the proposed compounds with the highest binding energy.

Benzimidazole (BNIMZ) and benzothiazole (BNTZA) based compounds are studied to understand their binding features with poly-A.poly-T DNA sequence and their mode of binding is also explored. According to thermal denaturation data, BNTZA slightly favors DNA stability with a 2.9 degrees C advantage over BNIMZ. The DNA conformational stability of the B DNA form was recorded with and without ligands by circular dichroism. The estimated docking scores support the findings from the UV denaturation investigation, and we observed that BNTZA had a higher docking score than BNIMZ. With the help of 50 ns MD simulations, additional conformational analyses have been performed. Both compounds effectively bind to the minor-grooves of AT-rich DNA sequence with a favorable binding free energy in accordance with the RMSD analysis, and pucker distribution of deoxyribose sugars. Future oligonucleotide therapies may be benefited because of the current discovery.

Over the course of three decades, benzimidazole as well as benzothiazole and its derivatives have been extensively investigated in oligo-nucleotide therapy for their properties. These derivatives serve as valuable building blocks for creating pharmaceutical and biologically active molecules. With applications ranging across various therapeutic domains, including antiulcer, anticancer, and anthelmintic treatments, substituted benzimidazole/ benzothiazole derivatives have proven their versatility. This review provides a systematic and comprehensive overview of the latest advancements in benzimidazole/ benzothiazole-based compounds within medicinal chemistry. These compounds exhibit diverse pharmacological activities such as anticancer, antibacterial, antifungal, anti-inflammatory, analgesic, anti-HIV, antioxidant, anticonvulsant, antitubercular, antidiabetic, antileishmanial, antihistaminic, antimalarial properties, among others. By presenting insights into the substitution patterns around the benzimidazole/benzothiazole nucleus, this review aims to assist medicinal chemists in developing structure-activity relationships (SAR) for benzimidazole/benzothiazole-based drugs and compounds, thereby aiding in the advancement of medicinal research.

In the present study, the degradation process of piperazine (PP) immobilized silica gel (SiPP) is investigated under dynamic conditions. The degradation of SiPP is studied with thermogravimetric analyzer (TGA). The kinetics of degradation process is analyzed by Kissinger method, Flynn–Wall–Ozawa's (FWO) method, and Deconvolution method. It is found that degradation of SiPP can be described by parallel independent two-portion process model, which includes two processing state of the system (marked by processes 1 and 2), where process 1 and 2 can be attributed to decomposition processes of organic moiety attached on silica surface. The apparent activation energy ( E a ) is calculated by Flynn–Wall–Ozawa's (FWO) method and deconvolution method.

Development of novel nano therapeutic material is of great interest among the researchers and with continuous advancement in nanotechnology, dendrimer a monodispersed unimicellar nanosize drug carrier with spacious globular 3D architecture in which the drug can be encapsulated is widely explored. This encapsulation of drug improves its pharmacokinetic and pharmacodynamics properties and more importantly enhances their bioavailability. A dendrimer based drug delivery system is a boon in targeted drug delivery. Its applications are not restricted to the pharmaceutical or medical field but also in other fields of science. The presence of various functional groups on the periphery has made their surface modifiable with therapeutic drugs, diagnostic agents, and targeting ligands. The vast surface area shows its capability to be used as a catalyst in chemical reactions too. And its biocompatibility makes its use much more effective and safer than other nano-carriers. This review tries to give a comprehensive description of this nano therapeutic, its properties, characteristics, method of synthesis, pharmacokinetics, toxicity, and recent applications in various fields, which can help the researchers for producing more promising outcomes of the dendrimers.

Synthetic modification of oligodeoxynucleotides (ODNs) via conjugation to nucleic acid binding small molecules can improve hybridization and pharmacokinetic properties. In the present study, five Hoechst 33258 derived benzimidazoles were conjugated to T rich ODNs and their hybridization effectiveness was tested. Thermal denaturation studies revealed significant stabilization of complementary duplexes by ODN-benzimidazole conjugates, with the extent of stabilization being highly dependent on the length of the linker between DNA and benzimidazole. The increases in thermal stability were determined to be due to the binding of the benzimidazole moiety to the duplex. Circular dichroism and molecular modeling studies provided insights toward the influence of conjugation on duplex structure and how linker length impacts placement of the benzimidazole moiety in the minor groove. Furthermore, thermal denaturation studies with the complementary strand containing a single base mismatch or being RNA revealed that covalent conjugation of benzimidazoles to an ODN also enhances the sequence specificity. The fundamental studies reported herein provide a strategy to improve the stability and specificity properties of the ODN probes, which can be of use for targeting and diagnostics applications.

Remdesivir, a C-nucleotide prodrug binds to the viral RNA-dependent-RNA polymerase (RdRp) and inhibits the viral replication by terminating RNA transcription prematurely. It is reported in literature that interaction between the C-1’β–CN moiety of Remdesivir (RDV) and the Ser861 residue in RdRp enzyme, causes a delayed chain termination during the RNA replication process and is one of the important aspect of its mechanism of action. In the pursuance of increasing the biological activity of RDV and enhancing the SAR studies, against RNA viruses, we have designed its fourteen C1’β substituted analogs, 10 –23 bearing 4/5-membered heterocyclic rings. The docking and 100 ns molecular dynamics (MD) simulations of 10-23 to the RdRp protein (PDB ID: 7L1F) revealed important interactions between 2’,3’-diol, oxo group of phosphoramidate, nitrogen residues of heterocyclic rings of synthetic molecules with Arg555, Arg553, Ser759, Cys622, Asn691, Asp623 amino acid residues of protein. The docking score of 2-ethylbutyl ((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f] [1], [2], [4]triazin-7-yl)-3,4-dihydroxy-5-(1H-1,2,3-triazol-4-yl)tetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)-L-alaninate, 11 was found to be the higher than RDV among 14 new compounds i.e. -5.20 kcal/mol. Out of 3 compounds, 10, 12 and 13 submitted for MD simulations and Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) analysis, trifluoro-oxadiazole derivative, 13 showed higher binding energy as compared to Remdesivir. The predicted ADMET properties of 14 compounds showed their potential for being drug candidates. The present study suggests that substitution at the C1’β position by 4/5-membered rings plays an important role in the interactions between nucleoside/tide and target protein.

Natural fiber-embedded polymer matrix composite offers a high strength-to-weight ratio, is eco-friendly, is economic, and has a good flexural strength to fulfil various engineering applications. During the fabrication, researchers faced the challenges of incompatibility, moisture absorption, low fracture toughness, and wear performance. This research focuses on the Roselle fiber subjected to alkali treatment (NaOH), which bonded with polypropylene matrix enriched by the inclusions of 3, 6, and 9 wt% of bryophyllum pinnatum leaf waste-derived silica nanoparticle synthesized via injection molding. The effects of fiber and nano-silica content on density, porosity, surface morphology, water absorption, microhardness, flexural strength, and fracture toughness of polypropylene composites were studied. The composite containing 25 wt% of NaOH-treated Roselle fiber blended with 9 wt% nano-silica particle (PPRFS3) offered less porosity (0.58%), and homogenous fiber and particle distribution in polypropylene matrix was confirmed via surface morphology. The results were improved microhardness (114 +/- 1.05 HV), superior flexural strength of 128.67 +/- 0.85 MPa, good fracture toughness of 2.32 MPa m(1/2), and a low water absorption rate of 0.0975%.

Purpose Composting is known since long for reducing the use of synthetic chemical fertilizers. These fertilizers are applied to the crops for the supply of required macro/micronutrients. The present study describes how to decompose biodegradable solid wastes quickly into compost without harming the environment. Method The microbial inoculums were developed from cow dung concentrate. The cow dung concentrate was mixed with water. The cow dung concentrates, and water mixture was then mixed with another water solution containing Jiggery. After a week, a creamy layer was observed to have formed. This confirms the development of microbial inoculum. Results After 2-3 days, temperature started to increase slowly. On the 15th day, temperature of the compost pile was 40 degrees C. At this temperature, the waste changed its colour and showed rapid decomposition. On the 25th day, temperature was noted to be around 60 degrees C. This showed the completion of the process. After 30 days, the compost was ready and showed signs of the process of maturation. Decrease in temperature confirmed completion of maturation process and complete conversion into compost. Conclusion The cow dung microbial inoculum consists of decomposing bacteria, protozoa and fungi which are effective to convert biodegradable waste into bio-fertilizer. The regular application of synthetic fertilizers causes adverse effect on greenhouse, environmental pollution, killing of earthworms and other beneficial micro-organisms of the soil, marine inhabitants, depletion of ozone layer, increase of toxicity among human beings due to excessive heavy metals, spoilage of soil fertility, and change in the soil pH.

The study aims to explore whether drugs (Bentaluron, Ethoxazolamide, Lubeluzole, Pramipexole, Probenzole, Riluzole, Viozan and Zopolrestat) that were originally developed for specific indications have the capability to interact with DNA sequences. If these drugs exhibit binding affinity to the studied DNA sequences, it suggests that they may have additional therapeutic applications beyond their original intended uses. Molecular docking is a computational technique used to predict the binding affinity and binding modes of molecules, such as drugs, to biological macromolecules, here DNA. In this study, docking is employed to simulate the interactions between the drugs with the two different oligonucleotides. The observation that these drugs bind differentially to various DNA duplexes suggests that their interactions with DNA are sequence-specific. This finding could be significant for designing drugs that target specific DNA sequences associated with diseases. The other functional possibilities of known drugs with DNA recognitions might be helpful in drug repurposing purposes with the findings of present study.

Measurements on excess molar volume by using dilatometer have been made for mixtures of Cyclohexanone with 1-chlorobutane, acetylene tetrachloride, Chloroform and 1,3 dichloropropane at 303.15K and under atmospheric pressure in the liquid state. The obtained data have been fitted with the help of polynomial Redlich-Kister equation and discussed with the point view of molecular interactions in the liquid state. The values of VE have been found to be negative in sign for the mixtures of Cyclohexanone with 1-chlorobutane, acetylene tetrachloride, and chloroform whereas it is positive in sign with 1,3-dichloropropane. The results obtained may be attributed to donor-acceptor interaction for all components in the liquid state.