Discovery of novel 6-(piperidin-1-ylsulfonyl)-2H-chromenes targeting α-glucosidase, α-amylase, and PPAR-γ: Design, synthesis, virtual screening, and anti-diabetic activity for type 2 diabetes mellitus.

A new series of 2H-chromene-based sulfonamide derivatives 3-12 has been synthesized and characterized using different spectroscopic techniques. The synthesized 2H-chromenes were synthesized by reacting activated methylene with 5-(piperidin-1-ylsulfonyl)salicylaldehyde through one-step condensation followed by intramolecular cyclization. Virtual screening of the designed molecules on α-glucosidase enzymes (PDB: 3W37 and 3A4A) exhibited good binding affinity suggesting that these derivatives may be potential α-glucosidase inhibitors. In-vitro α-glucosidase activity was conducted firstly at 100 µg/mL, and the results demonstrated good inhibitory potency with values ranging from 90.6% to 96.3% compared to IP = 95.8% for Acarbose. Furthermore, the IC50 values were determined, and the designed derivatives exhibited inhibitory potency less than 11 µg/mL. Surprisingly, two chromene derivatives 6 and 10 showed the highest potency with IC50 values of 0.975 ± 0.04 and 0.584 ± 0.02 µg/mL, respectively, compared to Acarbose (IC50 = 0.805 ± 0.03 µg/mL). Moreover, our work was extended to evaluate the in-vitro α-amylase and PPAR-γ activity as additional targets for diabetic activity. The results exhibited moderate activity on α-amylase and potency as PPAR-γ agonist making it a multiplet antidiabetic target. The most active 2H-chromenes 6 and 10 exhibited significant activity to PPAR-γ with IC50 values of 3.453 ± 0.14 and 4.653 ± 0.04 µg/mL compared to Pioglitazone (IC50 = 4.884±0.29 µg/mL) indicating that these derivatives improve insulin sensitivity by stimulating the production of small insulin-sensitive adipocytes. In-silico ADME profile analysis indicated compliance with Lipinski's and Veber's rules with excellent oral bioavailability properties. Finally, the docking simulation was conducted to explain the expected binding mode and binding affinity.

Innovation of 6-sulfonamide-2H-chromene derivatives as antidiabetic agents targeting α-amylase, α-glycosidase, and PPAR-γ inhibitors with in silico molecular docking simulation.

A new series of 2-imino or 2-oxo-2H-chromene-6-sulfonamide derivatives 2-9 with potential anti-diabetic activity were designed and synthesized. The new 6-sulfonamide chromenes were synthesized by reacting 3-formyl-4-hydroxybenzenesulfonyl chloride with activated methylene derivatives in the presence of ammonium acetate as a catalyst. The structure of the products was confirmed by spectroscopic analysis. All the designed derivatives 2-9 were evaluated for their activity against α-amylase and exhibited inhibitory percentage values higher than 93% at 100 µg mL-1. Additionally, the IC50 values represented a variable degree of activity with two derivatives 2 and 9 exhibiting the most promising derivative results with IC50 values of 1.76 ± 0.01 and 1.08 ± 0.02 µM, respectively, compared to Acarbose (IC50 = 0.43 ± 0.01 µM). Additionally, these derivatives showed potency against the α-glucosidase enzyme with IC50 values of 0.548 ± 0.02 and 2.44 ± 0.09 µg mL-1, compared to Acarbose (0.604 ± 0.02 µg mL-1). Moreover, the in vitro PPAR-γ transactivation assay revealed that chromene-6-sulfonamide derivatives 2 and 9 exhibited potential PPAR-γ activity with IC50 values of 3.152 ± 0.03 and 3.706 ± 0.32 µg mL-1, respectively, compared to Pioglitazone (4.884 ± 0.29 µg mL-1). This indicates that these derivatives have insulin sensitivity and glucose metabolism activity. The in silico ADMET prediction showed that these derivatives have an acceptable range of oral bioavailability, drug-likeness, and a safe toxicity profile, including being non-cytotoxic, non-mutagenic, non-immunotoxic, and non-carcinogenic. Finally, computational docking analysis demonstrated the ability of these derivatives to interact with α-amylase, α-glucosidase, and PPAR-γ enzymes, with confirmed successful placement due to good binding energy values and various interactions within the pocket.

Correction to "Anticorrosion Agents for Carbon Steel in Acidic Environments: Synthesis and Quantum Chemical Analysis of New Schiff Base Compounds with Benzylidene".

[This corrects the article DOI: 10.1021/acsomega.3c05790.].

Investigation of natural compounds as methyltransferase inhibitors against dengue virus: an in silico approach.

The global challenge posed by Dengue virus (DENV) infection persists, exacerbated by the absence of specific antiviral therapies. The viral methyltransferase (MTase) enzyme, crucial for viral RNA methylation and immune system evasion, has emerged as a promising drug target for combating Dengue fever. In this study, a comprehensive exploration of natural compounds derived from the COCONUT database was conducted, selecting 224 compounds based on their structural similarity to the native substrate of the MTase enzyme, S-adenosyl-L-methionine (SAM). Employing virtual screening techniques, four natural compounds (CNP0307160, CNP0082902, CNP0449158, and CNP0296775) with acceptable docking scores were selected for further re-docking after geometry optimization by the DFT method. Re-docking analyses unveiled significant interactions, including hydrogen bonds and hydrophobic interactions, between these selected ligands and the MTase protein. To gain deeper insights into the dynamic stability of these complexes, we conducted molecular dynamics simulations which showed lower RMSD values for CNP0307160, CNP0082902, and CNP0296775 when compared to the reference molecule. Furthermore, we assessed the structural and dynamic stability of the protein-ligand complexes through free binding energy calculations and Principal Component Analysis (PCA) of the simulation trajectories. In these analyses, the CNP0296775 compound exhibited promising results compared to the other three compounds. The cumulative findings of these investigations underscore the potential of CNP0296775 as a strong inhibitor of DENV MTase, thus offering a promising starting point for its further experimental validation and optimization.Communicated by Ramaswamy H. Sarma.

The Impact of Corrosion Inhibitors in Desalination Systems.

In this review, the importance of corrosion inhibitors in desalination plants is briefly discussed, with an emphasis on the various types for effective corrosion control techniques. The review highlighted the most significant corrosion inhibitors used in desalination plants for minimizing the corrosiveness of the source water throughout pretreatment, reverse osmosis, and post-treatment stages. Water composition, temperature and pressure, pH, dissolved oxygen, flow velocity, chloride content, fouling, and scaling are all described as factors affecting corrosion in desalinated water. The types of corrosion inhibitors used in desalination plants are summarized, including inorganic inhibitors, organic inhibitors, and eco-friendly inhibitors. Environmental issues and long-term inhibition are highlighted briefly.

Anticorrosion Agents for Carbon Steel in Acidic Environments: Synthesis and Quantum Chemical Analysis of New Schiff Base Compounds with Benzylidene.

Novel Schiff bases (SBs), namely, N1,N2-bis(2-(((E)-4-chlorobenzylidene)amino)ethyl)ethane-1,2-diamine (I), N1,N2-bis(2-(((E)-4-(dimethylamino)benzylidene)amino)ethyl)ethane-1,2-diamine (II), and N1,N'1-(ethane-1,2-diyl)bis(N2-((((Z)-4-dimethylamino)benzylidene) amino)methylethane-1,2-diamine) (III), were prepared and characterized by using elemental analysis, IR, and 1H NMR spectroscopy. For assessing carbon steel in diverse settings, with and without inhibitors at varying concentrations, electrochemical frequency modulation (EFM), electrochemical impedance spectroscopy (EIS), and potentiodynamic polarization (PP) techniques were employed. The results showed that the synthesized inhibitors effectively decreased the corrosion rate of carbon steel in acidic media and the inhibition efficiency reached up to 93% for compound III at a concentration of 250 ppm. In addition, all prepared compounds were successful as anticorrosion agents, and the inhibition mechanism followed chemisorption from the Langmuir isotherm. The data obtained from the theoretical analysis show that the efficiency of the prepared compounds was in the order III < II < I. Furthermore, quantum chemical calculations were performed to gain insight into the electronic structure of the compounds. The analysis of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) showed that compound III had the highest surface coverage due to its specific molecular structure and spacer. This observation agreed well with the Langmuir adsorption data.

Repurposing Anti-Dengue Compounds against Monkeypox Virus Targeting Core Cysteine Protease.

The monkeypox virus (MPXV) is an enveloped, double-stranded DNA virus belonging to the genus Orthopox viruses. In recent years, the virus has spread to countries where it was previously unknown, turning it into a worldwide emergency for public health. This study employs a structural-based drug design approach to identify potential inhibitors for the core cysteine proteinase of MPXV. During the simulations, the study identified two potential inhibitors, compound CHEMBL32926 and compound CHEMBL4861364, demonstrating strong binding affinities and drug-like properties. Their docking scores with the target protein were -10.7 and -10.9 kcal/mol, respectively. This study used ensemble-based protein-ligand docking to account for the binding site conformation variability. By examining how the identified inhibitors interact with the protein, this research sheds light on the workings of the inhibitors' mechanisms of action. Molecular dynamic simulations of protein-ligand complexes showed fluctuations from the initial docked pose, but they confirmed their binding throughout the simulation. The MMGBSA binding free energy calculations for CHEMBL32926 showed a binding free energy range of (-9.25 to -9.65) kcal/mol, while CHEMBL4861364 exhibited a range of (-41.66 to -31.47) kcal/mol. Later, analogues were searched for these compounds with 70% similarity criteria, and their IC50 was predicted using pre-trained machine learning models. This resulted in identifying two similar compounds for each hit with comparable binding affinity for cysteine proteinase. This study's structure-based drug design approach provides a promising strategy for identifying new drugs for treating MPXV infections.

Electrochemical and theoretical investigations of favipiravir drug performance as ecologically benign corrosion inhibitor for aluminum alloy in acid solution.

Aluminum-silicon alloys have become a preferred option in the automotive and aerospace industries thanks to their fault-tolerant process ability and reasonable static characteristics at relatively affordable costs. This study aimed to investigate the use of favipiravir (FAV) drug as a biocompatible and eco-friendly inhibitor to protect aluminum alloy (AlSi) surface in an aggressive acid environment (1.0 M HCl). The electrochemical measurements declare that FAV is categorized as an inhibitor of mixed type with a cathodic effect. At 100 ppm, FAV had the highest inhibitory efficiency (96.45%). FAV is associated with lower double-layer capacitance values and more excellent charge-transfer resistance. These results show that AlSi corrosion in 1.0 M HCl is reduced in the presence of FAV. The Langmuir model is well-suited to the FAV adsorption behavior (R2 ≈ 1). Chemisorption is the primary adsorption in this environment. The theoretical calculation studies corrosion inhibitors' molecular structure and behavior. Different quantum chemical properties of the FAV have been calculated, including energy difference (ΔE), softness, global hardness, and energy of back-donation depending on the highest occupied and lowest unoccupied molecular orbitals. In addition, Mulliken and Fukui's population analysis and the Molecular Electrostatic Potential map represent the electron distribution and the molecule's active centers. Experimental findings and quantum chemical computations matched, and FAV is recommended as a green corrosion inhibitor.

Computer-assisted discovery of safe and effective DprE1/ aaRSs Inhibitors against TB utilizing Drug Repurposing approach.

BACKGROUND: The emergence of various drug-resistant strains of Mycobacterium tuberculosis compelled medicinal chemists to expedite the discovery of novel, safer alternatives to present regimens. Decaprenylphosphoryl-ß-d-ribose 2'-epimerase (DprE1), an essential component of arabinogalactan biosynthesis, has been considered a novel target for developing new inhibitors against Tuberculosis. We aimed to discover DprE1 inhibitors utilizing the drug repurposing approach. METHODS: A structure-based virtual screening of FDA and world-approved drugs database was carried out, and initially, 30 molecules were selected based on their binding affinity. These compounds were further analyzed by molecular docking with extra-precision mode, MMGBSA binding free energy estimation, and prediction of ADMET profile. RESULTS: Based on the docking results and MMGBSA energy values- ZINC000006716957, ZINC000011677911, and ZINC000022448696 were identified to be the top three hit molecules with good binding interactions inside the active site of DprE1. These hit molecules were subjected to molecular dynamics (MD) simulation for a period of 100 ns to study the dynamic nature of the binding complex. MD results were in accordance with molecular docking and MMGBSA analysis showing protein-ligand contacts with key amino acid residues of DprE1. CONCLUSION: Based on their stability throughout the 100 ns simulation, ZINC000011677911 was the best in silico hit with an already known safety profile. This molecule could lead to future optimization and development of new DprE1 inhibitors.

Comparative Proteomics and Genome-Wide Druggability Analyses Prioritized Promising Therapeutic Targets against Drug-Resistant Leishmania tropica.

Leishmania tropica is a tropical parasite causing cutaneous leishmaniasis (CL) in humans. Leishmaniasis is a serious public health threat, affecting an estimated 350 million people in 98 countries. The global rise in antileishmanial drug resistance has triggered the need to explore novel therapeutic strategies against this parasite. In the present study, we utilized the recently available multidrug resistant L. tropica strain proteome data repository to identify alternative therapeutic drug targets based on comparative subtractive proteomic and druggability analyses. Additionally, small drug-like compounds were scanned against novel targets based on virtual screening and ADME profiling. The analysis unveiled 496 essential cellular proteins of L. tropica that were nonhomologous to the human proteome set. The druggability analyses prioritized nine parasite-specific druggable proteins essential for the parasite's basic cellular survival, growth, and virulence. These prioritized proteins were identified to have appropriate binding pockets to anchor small drug-like compounds. Among these, UDPase and PCNA were prioritized as the top-ranked druggable proteins. The pharmacophore-based virtual screening and ADME profiling predicted MolPort-000-730-162 and MolPort-020-232-354 as the top hit drug-like compounds from the Pharmit resource to inhibit L. tropica UDPase and PCNA, respectively. The alternative drug targets and drug-like molecules predicted in the current study lay the groundwork for developing novel antileishmanial therapies.

Recent Advancement in Drug Design and Discovery of Pyrazole Biomolecules as Cancer and Inflammation Therapeutics.

Pyrazole, an important pharmacophore and a privileged scaffold of immense significance, is a five-membered heterocyclic moiety with an extensive therapeutic profile, viz., anti-inflammatory, anti-microbial, anti-anxiety, anticancer, analgesic, antipyretic, etc. Due to the expansion of pyrazolecent red pharmacological molecules at a quicker pace, there is an urgent need to put emphasis on recent literature with hitherto available information to recognize the status of this scaffold for pharmaceutical research. The reported potential pyrazole-containing compounds are highlighted in the manuscript for the treatment of cancer and inflammation, and the results are mentioned in % inhibition of inflammation, % growth inhibition, IC50, etc. Pyrazole is an important heterocyclic moiety with a strong pharmacological profile, which may act as an important pharmacophore for the drug discovery process. In the struggle to cultivate suitable anti-inflammatory and anticancer agents, chemists have now focused on pyrazole biomolecules. This review conceals the recent expansion of pyrazole biomolecules as anti-inflammatory and anticancer agents with an aim to provide better correlation among different research going around the world.

Investigation on the evolution of hydrothermal biochar.

The objective of this study was to visualize trends and current research status of hydrothermal biochar research through a bibliometric analysis by using CiteSpace software. The original article data were collected from the Web of Science core database published between 2009 and 2020. A visual analysis network of national co-authored, institutional co-authored and author co-authored articles was created, countries, institutions and authors were classified accordingly. By visualizing the cited literature and journal co-citation networks, the main subject distribution and core journals were identified respectively. By visualizing journal co-citations, the main research content was identified. Further the cluster analysis revealed the key research directions of knowledge structure. Keyword co-occurrence analysis and key occurrence analysis demonstrate current research hotspots and new research frontiers. Through the above analysis, the cooperation and contributions of hydrothermal biochar research at different levels, from researchers to institutions to countries to macro levels, were explored, the disciplinary areas of knowledge and major knowledge sources of hydrothermal biochar were discovered, and the development lineage, current status, hotspots and trends of hydrothermal biochar were clarified. The results obtained from the study can provide a reference for scholars to gain a deeper understanding of hydrothermal biochar.

The Therapeutic and Prophylactic Potential of Quercetin against COVID-19: An Outlook on the Clinical Studies, Inventive Compositions, and Patent Literature.

Quercetin is a phenolic flavonol compound with established antioxidant, anti-inflammatory, and immuno-stimulant properties. Recent studies demonstrate the potential of quercetin against COVID-19. This article highlighted the prophylactic/therapeutic potential of quercetin against COVID-19 in view of its clinical studies, inventions, and patents. The literature for the subject matter was collected utilizing different databases, including PubMed, Sci-Finder, Espacenet, Patentscope, and USPTO. Clinical studies expose the potential of quercetin monotherapy, and also its combination therapy with other compounds, including zinc, vitamin C, curcumin, vitamin D3, masitinib, hydroxychloroquine, azithromycin, and ivermectin. The patent literature also examines claims that quercetin containing nutraceuticals, pharmaceuticals, and dietary supplements, alone or in combination with other drugs/compounds, including favipiravir, remdesivir, molnupiravir, navitoclax, dasatinib, disulfiram, rucaparib, tamarixin, iota-carrageenan, and various herbal extracts (aloe, poria, rosemary, and sphagnum) has potential for use against COVID-19. The literature reveals that quercetin exhibits anti-COVID-19 activity because of its inhibitory effect on the expression of the human ACE2 receptors and the enzymes of SARS-CoV-2 (MPro, PLPro, and RdRp). The USFDA designated quercetin as a "Generally Recognized as Safe" substance for use in the food and beverage industries. It is also an inexpensive and readily available compound. These facts increase the possibility and foreseeability of making novel and economical drug combinations containing quercetin to prevent/treat COVID-19. Quercetin is an acidic compound and shows metabolic interaction with some antivirals, antibiotics, and anti-inflammatory agents. Therefore, the physicochemical and metabolic drug interactions between quercetin and the combined drugs/compounds must be better understood before developing new compositions.