Some new 5-fluoro-1H-indole-2-carboxamide hybrids (6a-g) were synthesized by a multi-step synthetic route. A key step involved the formation of the amide bond between the indole-2-carboxylic acid and various aromatic amines in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide HCl/1-hydroxybenzotriazole. The pharmacological potential of the structurally elucidated series was established through diverse antioxidant (2,2-diphenyl-1-picrylhydrazyl [DPPH]/ferric reducing antioxidant power [FRAP]) and antimicrobial screening. Within the synthesized library, compound 6g, emerged as the most potent radical scavenger, demonstrating antioxidant capacities (DPPH: 74.5 +/- 0.01; FRAP: 3.198 +/- 0.03) that rival the standard reference, ascorbic acid. Both 6g and 6a displayed a broad spectrum of action, successfully inhibiting diverse fungal pathogens alongside Gram-positive and Gram-negative bacteria. The SAR analysis confirms that electron-rich aryl substitutions are pivotal for optimizing bioactivity, positioning these fluorinated indole carboxamides as versatile scaffolds for future medicinal development.
Synthesis of an array of new molecular hybrids, 1-benzyl-3,5-bis[(1,3-diaryl-1H-pyrazol-4-yl)methylene] piperidin-4-ones (3a-3f) has been accomplished from pyrazole based carbaldehydes and N-benzylpiperidin-4-one via Claisen-Schmidt reaction. Cytotoxicity evaluation reveals that the para-bromo moiety possessing hybrid 3a displayed the most potent activity (half-maximal inhibitory concentration: similar to 12 and similar to 37 mu M against SW1990 and AsPC1 pancreatic cancer cells, respectively) among the synthesized ones. Molecular docking examination exposes the potent hybrid 3a communicates strongly with B-cell lymphoma-2 protein with a binding energy -9.4 kcal.mol(-1).
Some new 2H-naphtho[1,2-b][1,4]oxazin-2-one derivatives 11a-d were synthesized through a multi-step process beginning with the esterification of readily available hydroxy compounds 1a-d. The esters 3a-d, on reaction with hydrazine hydrate, produced hydrazides 4a-d. A cyclization reaction between 2-nitrosonaphthalen-1-ol 5 and ethyl acetoacetate 6 formed a substituted oxazin-2-one derivative 7. The next step was the formation of chalcone 9 through the reaction of oxazin-2-one 7 with terephthalaldehyde 8, followed by the reaction of chalcone 9 with hydrazide 4a-d, which delivered the final 2H-naphtho[1,2-b][1,4]oxazin-2-one derivatives 11a-d.
We have synthesized some new 4-phenyl-4,5-dihydro-1H-benzo[f][1,3,5]triazepin-2(3H)-one derivatives by a green, facile approach involving a one-pot three-component condensation involving various aldehydes with o-phenylenediamine and urea in ethanol as solvent and sodium tungstate as a catalyst. The reaction provided good to excellent yields in a short time. Molecular docking with breast cancer target protein 3ERT and absorption, distribution, metabolism, and excretion studies indicated good binding energies and drug-like properties. The derivatives also showed notable in vitro anticancer activity against MCF-7 cells, highlighting their potential as new anticancer agents. Biological evaluations are ongoing.
Post-COVID-19, people are suffering from multiple diseases at the same time. Therefore, a medication/ molecule is needed that targets multiple diseases, and xanthone is one such moiety. Xanthone is a basic active compound having a tricyclic planar bone and a pyran ring. The fused pyran ring carries a phenyl ring on each side. In the present study, this moiety was exploited to ensure its diverse pharmacological activities. Hence, in the future, it can be a savior of mankind as it can be used to treat patients with multiple diseases. In silico studies were performed on thirty designed novel 3-aminoalkoxy derivatives of xanthone. Molecular docking was carried out on the test ligands with receptors, peroxisome proliferator-activated receptor gamma (PPAR-& upsih;), cyclooxygenase-2 (COX-2), plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS), and xanthine oxidoreductase, respectively. Among all the designed ligands, LIG14 showed the best docking score of-12.86, -10.1, and-9.9 kcal/mol against receptors, PPAR-& upsih;, COX-2, and PfDHFR-TS, respectively, for antidiabetic, analgesic, and anti-malarial activity. Furthermore, other designed ligands than LIG14 also showed appreciable activity. The interactions observed in molecular docking were preserved during the molecular dynamic simulation. Finally, it was concluded that as all our designed ligands showed significant binding potential and also LIG14 possessed to be highly active against three different receptors, further in vitro and in vivo studies should be conducted so that it can be used to treat patients with multiple diseases.
The synthesis of some new 1-(aroyl)-4-([2-hydroxyphenyl] methylidene) pyrazolidine-3,5-diones (5A-O) was accomplished by the reaction of 1-(aroyl) pyrazolidine-3,5-diones (4A-O) with o-hydroxybenzaldehyde by Knoevenagel condensation reaction. An investigation of antioxidant activity was performed using the 2,2-diphenyl-1-picrylhydrazyl assay, with ascorbic acid as the standard. Several compounds exhibited significant free radical-scavenging activity, which may be attributed to the presence of electron-donating substituents and a phenolic hydroxyl group in the molecular framework. The derivatives 5O (half-maximal inhibitory concentration[IC50] = 3.047 +/- 0.05 & micro;g/mL), 5E (IC50 = 3.376 +/- 0.02 & micro;g/mL), 5H (IC50 = 3.647 +/- 0.07 & micro;g/mL), 5L (IC50 = 3.985 +/- 0.04 & micro;g/mL), and 5C (IC50 = 4.487 +/- 0.04 & micro;g/mL), showed maximum potency among all the synthesised derivatives compared to standard ascorbic acid (IC50 = 10.221 +/- 0.02 & micro;g/mL).
A new oxadiazole derivative, namely, 2-phenyl-5-(2-((1E,2E)-3-phenylallylidene)hydrazineyl)-1,3,4-oxadiazole, was synthesized and coordinated with some transition metal ions (CrIII, CoII, NiII, and CuII). These complexes were characterized by a set of spectroscopic techniques such as proton nuclear magnetic resonance, Fourier-transform infrared spectroscopy, and mass spectra. The optimized geometric structures and the molecular orbitals (highest occupied molecular orbital and lowest unoccupied molecular orbital) were computed using density functional theory at B3LYP/6-31G+(d,p) level by the Gaussian program. The magnetic susceptibility results were in agreement with the theoretical optimization. These experimental and computational simulations suggested octahedral geometries for Cr(& Iukcy;& Iukcy;& Iukcy;) and tetrahedral geometry for Co(& Iukcy;& Iukcy;) and square planar geometry for Ni(II) and Cu(& Iukcy;& Iukcy;). Computational simulations showed that the oxadiazole-Schiff base was a promising corrosion inhibitor.
alpha,(3-Unsaturated ketones 4a-c were synthesized from Khellin (1) and converted into (E)-4,7-dimethoxy-5-(2-phenyl-2,3-dihydrobenzo[b][1,4] derivatives of thiazepin-4-yl)benzofuran-6-ol (6a-c) by reaction with 2-aminobenzothiol (5) in an acidic medium. Density functional theory/P3LYP theoretical calculations were carried out to verify the reaction mechanism for the formation of 6. According to molecular docking studies, these compounds serve as promising acetylcholinesterase (AChE) inhibitors, making them powerful agents for greater control in treatment development for neuronal degenerative disorders. Theoretical modeling studies indicate that these compounds have substantial binding affinities with the AChE active site. Their absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles, bioactivity scores, and medicinally relevant physicochemical properties were also thoroughly evaluated. The evaluations indicate that all derivatives should have good pharmacokinetic qualities and be non-carcinogenic.
In this study, new benzimidazole derivatives (BPH-1-BPH-8) were synthesized and tested for their anticonvulsant properties. The synthetic approach involved three steps (i) preparation of benzimidazole-2-carboxylic acid esters, (ii) formation of hydrazides by the hydrazinolysis of carboxylic esters with hydrazine hydrate, and (iii) the condensation of hydrazide with substituted phthalic anhydride to give target compounds. The anticonvulsant activity was tested through the maximal electroshock seizure animal model method, with phenytoin as a standard drug. Three compounds, BPH-3, BPH-5, and BPH-7, demonstrated significant protection against electrically induced seizures, thus implying that the presence of electron-withdrawing groups at the aromatic ring enhances the anticonvulsant potency.
The chemical industry is rapidly transitioning toward cloud-enabled and high-performance computational infrastructures to support large-scale simulations, molecular modeling, reaction optimization, and data-intensive research. Efficient virtual machine (VM) allocation has become essential for improving throughput, scalability, costefficiency, and energy utilization for quantum chemical calculations, molecular docking, and virtual screening involving heterocyclic libraries. This narrative review examines the integration of artificial intelligence (AI) and machine learning (ML) techniques in VM allocation within chemical industry settings, with particular emphasis on heterocyclic compound research and computational chemistry applications. Drawing upon numerous documented applications of VM-based cloud deployment in chemical and materials science workflows, the review synthesizes current advances in AI-driven scheduling algorithms, predictive resource provisioning, reinforcement learning-based allocation models, intelligent load balancing, and adaptive auto-scaling strategies. It further discusses how ML-enhanced VM orchestration supports computational tasks in heterocyclic chemistry, including reaction pathway prediction, molecular property modeling, drug discovery simulations, and process optimization. Overall, integrating AI and ML with VM allocation represents a promising and scalable approach for advancing intelligent, efficient, and sustainable computational infrastructures within the modern chemical industry.. KEYWORDS :Artificial intelligence, Machine learning, Virtual machines, Cloud computing, Resource allocation, Chemical industry, Heterocyclic compounds, Computational chemistry, High-performance computing, Predictive modeling.
A new series of isomeric disubstituted 3-(2-(4-(2,4-dichlorophenyl)thiazole-2-yl) hydrazonoindolin-2-ones (4-14) has been synthesized through one-pot three-component approach. The method involved the reaction of 2,4-dichlorophenacyl chloride (1), thiosemicarbazide (2), and disubstituted isomeric isatins (3) under conventional heating in ethanol-DMF mixture using a catalytic amount of glacial acetic acid.
Naringin is a naturally occurring flavonoid glycoside recognized for its moderate biological activity and strong metal-chelating ability. Exploring this property, a new cobalt-naringin complex was synthesized with a yield of 44.37% and subsequently characterized using comprehensive spectroscopic and thermal analytical techniques to confirm its coordination behavior and stability. The biological potential of the synthesized complex was systematically investigated through antimicrobial, antioxidant, anthelmintic, molluscicidal, and anticancer assays. Antimicrobial activity was evaluated against representative Gram-positive and Gram-negative bacteria (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa) as well as fungal strains (Aspergillus niger and Candida albicans). Antioxidant efficacy was assessed using standard free radical scavenging assays. The cytotoxic potential of naringin and complex was assessed against the Michigan Cancer Foundation-7 human breast cancer cell line using the MTT assay. Notably, it exhibited superior antimicrobial efficacy, particularly against S. aureus and C. albicans. The complex also showed improved antioxidant capacity, indicating increased free radical scavenging ability. Furthermore, in vitro anticancer evaluation indicated markedly reduced half-maximal inhibitory concentration value for the cobalt complex, confirming its enhanced cytotoxicity. Overall, coordination of naringin with cobalt markedly improves its multifunctional biological performance, highlighting its promise as a potential candidate for further pharmacological development.
An azomethine linkage-based chemosensor, namely, 4-(furan-2-ylmethyleneamino)-2,3-dimethyl-1-phenyl-1,2-dihydropyrazol-5-one was synthesized the condensation of biologically relevant 4-aminoantipyrine and furfural. The synthesized chemosensor exhibited a remarkable color change from colorless to light yellow in the presence of Al3+ ions in pure acetonitrile. The study indicated the non-covalent interactions between compound RM1 and Al3+ ions with a 2:1 binding stoichiometry and an association constant of 0.97 & times; 104 M-1. The detection and quantification limit of the synthesized compound for the analysis of Al3+ ions have been determined as 101.54 & micro;M and 338.50 & micro;M, respectively. To determine the practical utility of the synthesized compound, strip test kits incorporated with RM1 were prepared to provide on-site detection of aluminum ions, and a recovery percentage of 84-86% was observed. This compound was further evaluated for cytotoxicity against HeLa and Vero cell lines, where it emerged as a non-cytotoxic probe.
The indolyl analogs of chalcones, namely E-1-aryl-3-(1-methyl-1H-indol-3-yl)prop-2-en-1-ones (1a-g) were synthesized involving Claisen Schmidt reaction between 1-methylindole-3-carboxaldehyde and acetophenones by three Methods (A-C). The green approaches using ultrasound irradiations (Method B) and microwave irradiations (Method C) provided a significant improvement over the conventional approach (Method A), which afforded yields of only 62-78%. The anticancer effects of seven indole derivatives were evaluated on a SKOV-3 ovarian cancer cell line, with results between 1.061 +/- 0.17 and 43.34 +/- 0.36 & micro;M, with compound 1c being the most effective (IC50) and compound 1g was the least, with 290.8 +/- 9.325. Molecular docking of these compounds was conducted to study their interactions with epidermal growth factor receptor, estimated glomerular filtration rate (PDB ID 4HJO), and binding strength. Absorption, distribution, metabolism, excretion, and toxicity have identified indole derivatives as having beneficial qualities by examining the relationships between their structures, physical and chemical properties.
2-((3-(Substituted phenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)hydrazine-1-carbothioamides (2A-J) were reacted with phthalic anhydride in the presence of toluene to give corresponding phthalimide derivatives (P2A-J). The antimicrobial activity of the synthesized compounds was evaluated against a well-defined panel of microorganisms, including Gram-positive bacteria (Staphylococcus aureus, Streptococcus pyogenes), Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), and fungal strains (Candida albicans, Aspergillus niger) to provide a comprehensive assessment of their antibacterial and antifungal potential.
Background: Atherosclerosis (AS) is a chronic inflammatory disease driven by endothelial dysfunction and excessive activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome. 3,5,7-trihydroxy2-(4-hydroxy-3-methoxyphenyl)chromen-4-one, a flavonoid abundant in medicinal plants, has been reported to exhibit antiinflammatory and cardioprotective properties. However, its molecular mechanism in modulating NLRP3 remains unclear. Methods: To elucidate the molecular basis of 3,5,7-trihydroxy-2-(4-hydroxy-3-methoxyphenyl)chromen-4-one-mediated NLRP3 inhibition, a multi-computational strategy was employed, integrating density functional theory (DFT), molecular docking, molecular dynamic (MD) simulation, and molecular mechanics/generalized born surface area free energy decomposition. DFT calculations were used to characterize the molecular stability and electronic distribution of 3,5,7-trihydroxy-2-(4-hydroxy-3-methoxyphenyl) chromen-4-one. Molecular docking predicted potential binding residues within the NLRP3 active site. Subsequently, 200 ns MD simulations and free energy landscape (FEL) analyses were performed to assess the stability and dynamic behavior of the complex. Results: DFT analysis revealed a stable frontier orbital distribution conducive to hydrogen-bond formation. Docking and MD results demonstrated that 3,5,7-trihydroxy-2-(4-hydroxy-3-methoxyphenyl)chromen-4-one binds tightly within the NLRP3 pocket through hydrogen bonding and hydrophobic interactions, particularly involving Glu135, Leu242, and Trp245. The root mean square deviation and root mean square fluctuation profiles indicated high conformational stability, while the FEL map showed a single deep energy basin, confirming thermodynamic robustness. Free energy decomposition analysis revealed that van der Waals and electrostatic interactions were the primary driving forces for complex stabilization. Conclusion: This study provides inflammasome activation through stable binding and favorable energetic contributions, potentially mitigating inflammationassociated vascular injury. These findings offer a theoretical basis for developing 3,5,7-trihydroxy-2-(4-hydroxy-3-methoxyphenyl) chromen-4-one-derived inhibitors as promising therapeutic candidates for the prevention and treatment of AS.
Pyrazoline derivatives (3a-f) and their copper(II) complexes were synthesized and characterized using spectroscopic methods. The in vitro cytotoxic activities of selected compounds against the human cancer cell lines (MCF-7) and (A549) were evaluated by MTT assay. 1-(3-(2,4-Dimethoxyphenyl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)ethan-1-one (3f) displayed a significant cytotoxic activity with IC50 values of 30.39 and 31.34 mu g/mL, against MCF-7 and A549, respectively. Copper(II)-pyrazoline complex (3eCu) exhibited a significant cytotoxic activity, with IC50 values of 5.77 and 4.10 mu g/mL against MCF-7 and A549, respectively. Molecular docking study showed the best binding poses of 3f and copper(II)-pyrazoline complex (3eCu) with the proteins 5T92 and 4JPS, respectively. The absorption, distribution, metabolism, and excretion profile and pharmacokinetic predictions revealed that complex 3eCu met all parameters within acceptable ranges.
2-{[(1-Benzothiophen-3-yl)methylidene]amino}phenol (Schiff base) and its Co(II), Ni(II) and Cu(II) metal complexes were synthesized and screened for their antimicrobial and antifungal potential. The synthesized metal complexes were characterized using Fourier Transform Infrared, ultraviolet, high-resolution mass spectrometry and thermogravimetric analysis. All the metal complexes had co-ordination number 4 and possible distorted tetrahedral structure for Co(II) and distorted square planar structure for Ni(II) and Cu(II). ADME studies of the complexes were performed to gain their in silico properties.
A series of five new 4-amino-5-phenyl-1,2,4-triazole-3-thiol Schiff base derivatives (4a-4e) was rationally designed, and successfully synthesized by the condensation reaction between 4-amino-phenyl-4H-1,2,4-triazol-3-thiol and aromatic aldehydes, in silico absorption, distribution, metabolism, and excretion (ADME) studies were conducted using the Swiss ADME platform to assess drug-likeness and pharmacokinetic behavior. The predicted results indicated favorable physicochemical properties, good oral bioavailability, high gastrointestinal absorption, and compliance with Lipinski, Veber, and Egan rules, with no predicted blood-brain barrier permeability. The anticancer activity of the synthesized compounds was evaluated in vitro using MTT viability assay against the HepG2 human hepatocellular carcinoma cell line, with WRL-86 normal hepatic cells used for comparison. Compound 4a exhibited a concentration-dependent cytotoxic effect against HepG2 cells, while showing comparatively lower toxicity toward WRL-68 cells, suggesting a possible degree of selectivity toward cancer cells. However, the observed anticancer activity was modest and was more pronounced only at higher concentrations. Overall, the combined synthetic, structure, in silico ADME, and preliminary biological evaluation indicated that these 1,2,4-triazole-based Schiff base derivatives represent promising scaffolds for further structure optimization and extended biological investigations.
The presence of a carboxylic acid causes gastric burning; the removal of this group facilitates the development of more potent, safer, and selective cyclooxygenase (COX)-II inhibitors as anti-inflammatory agents. The paper represents an in silico study that aims at screening through the various stages for the optimization of triazolothiadiazole and triazolothiadiazine derivatives with COX-II inhibition. There was a total of 518 ligands were designed with different electron-withdrawing and donating group with different positions by using ChemDraw Ultra 8.0, and then systematically treated with drug-likeness filtering based on Lipinski Rule of Five. This was succeeded by pharmacophore screening, Drug likeness, Lead optimization, profiling, adverse drug reactions (Absorption, Distribution, Metabolism, Excretion, and Toxicity), molecular docking, toxicity prediction, density functional theory and molecular dynamics (MD) simulations. The compound pool was narrowed down upon successive screening stages, which came down to 6 lead ligands. Between them, ligand_163 was the most strongly binding (-10.0 kcal/mol), fairly toxic (median lethal dose: 1000 mg/kg, Class IV) and Energy Gap (Delta E Gap) 0.08785, which shows very soft and reactive, could be highly biologically active, and exhibited the most favorable by stability in MD over 100 ns trajectory. These data indicate that ligand_163 could be a successful candidate to be followed in experiments as an anti-inflammatory agent.
