Unveiling Naturally Occurring Green Tea Polyphenol Epigallocatechin-3-Gallate (EGCG) Targeting Mycobacterium DPRE1 for Anti-Tb Drug Discovery

The increasing rates of multidrug-resistant (MDR) and extremely drug-resistant (XDR) cases of tuberculosis (TB) strains are alarming, and eventually hampered the effective control of the pathogenic disease. Epigallocatechin gallate (EGCG) is a major polyphenolic constituent of green tea, which previously demonstrated in vitro potency against TB strains. However, efforts to elucidate the exact mechanism of the interaction are still ongoing. Aiming to elucidate the probable mechanism of its anti-TB action as decaprenylphosphoryl-beta-D-ribose 2′-epimerase (DprE) inhibition, we conducted a molecular modeling analysis. Our molecular docking analysis for a set of 65 bioactive compounds of tea realized that EGCG has the highest binding affinity (docking score: −142.98 kcal/mol) against DPRE (pdb id: 4p8c) from Mycobacterium tuberculosis. Further, a molecular dynamics analysis of 100 ns resulted in extreme stability of the ligand–protein complex. We further assessed the in silico pharmacokinetics and toxicities of the top three green tea polyphenols, based on the docking scores. Our results provide critical insights into the mechanism of action of EGCG and other green tea polyphenols, and their use as potential therapeutic agents (DprE1) against TB

Naturally Occurring Green Tea Polyphenols as Anti-Mycobacterial Agents

Tuberculosis (TB) is a global health burden especially in tropical countries. Extensive increments in MDR (Multidrug resistance (MDR): Resistance to at least both isoniazid and rifampicin.) and XDR (Extensive drug resistance (XDR): Resistance to any fluoroquinolone, and at least one of three second-line injectable drugs (capreomycin, kanamycin, and amikacin), in addition to multidrug resistance) tuberculosis highlights the ineffectiveness of established anti-TB agents. There is an urgent necessity to identify potent anti-TB agents with unique mechanisms. Green tea and Black tea polyphenols have great potential to inhibit viruses including SARS-COV-2, bacterial strains, etc. In this context, we have screened and identified 65 Green tea bioactive compounds against four mycobacterial pantothenate synthetase and enoyl acyl carrier enzymes. Our molecular docking results revealed that Theaflavin-3-gallate had a higher binding affinity against 2X22 and 3IVX targets with docking scores of −134.13 and −135.592 Kcal/mol, respectively. Furthermore, our molecular dynamics simulations for 10 ns resulted better stabilities of these complexes. We also evaluated in silico drug-likeness and toxicity profiles for the studied polyphenols. Our in silico toxicity analysis suggested that these polyphenols would exhibit lesser toxicity such as eye corrosion, skin irritations, etc. Thus, our present study would provide better insights on studying naturally occurring polyphenols as potential anti-TB agents

Formulation of Effervescent Compact Detergent Tablets with Unique Chemical Compositions

The tablet form of detergent powder is one of the new delivery systems of detergent. It is a compact form of detergent powder with highly active ingredients. The tablet form of detergent reduces the volume of the powder. Due to its compact format, it affects the transportation and packing cost. Thus, we aimed to formulate the unique detergent powder with the chemical combinations of various surface-active agents. The detergent formulation thus contains linear alkyl benzene sulphonate (LABSA), alfa sulfo methyl esters, sodium tripolyphosphate (STPP), sodium hydroxide (NaOH), sodium silicate, sodium sulphate, etc. In our study, the detergent powder is mixed with various disintegrating agents such as corn starch, sodium carboxymethyl cellulose (sodium CMC), silicic acid, sodium carbonate and citric acid. Our compact detergent powder showed better detergency properties. This helps to instantly disintegrate and disperse when contacted with water. Detergent powder composition in our currently formulated tablets caused effervescences and disintegrated within 30 s at room temperature in water. The tablet detergent showed better performance than market detergents

Synthesis and Anti-Tuberculosis Activity of Substituted 3,4-(dicoumarin-3-yl)-2,5-diphenyl Furans and Pyrroles

Increasing rates of multi-drug resistant (MDR) and extremely-drug resistant (XDR) cases of tuberculosis (TB) strains are alarming, and eventually hampered an effective control of the pathogenic disease. In the present study, nine derivatives of 2,3-bis(2-oxochromen-3-yl)-1,4-diphenyl-butane-1,4-dione (11a–c) and 3,4-(dicoumarin-3-yl)-2,5-diphenyl furans and pyrroles (12a–f) have been synthesized successfully. The experimental data for the anti-tuberculosis activity (using MABA assay) of 2,3-bis(2-oxochromen-3-yl)-1,4-diphenyl-butane-1,4-dione (11a–c) revealed that, in this series, compound 11a showed a better minimum inhibitory concentration of 1.6 μg/mL against Mycobacterium tuberculosis (H37 RV strain) ATCC No-27294, which was better than the MIC value of Pyrazinamide-3.125 μg/mL, Streptomycin-6.25 μg/mL and Ciprofloxacin-3.125 μg/mL. Our synthesis and in-vitro studies thus pointed out the moderate to good anti-TB profiles of substituted furans and pyrroles

Greener Synthesis, In-Silico and Theoretical Analysis of Hydrazides as Potential Antituberculosis Agents (Part 1)

Since several decades, our healthcare burden has been increased due to tremendous cases of multidrug-resistant (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) infections, especially in tropical countries. In the present study, we have synthesized ten hydrazides with the use of the greener Chitosan-derived catalyst. This catalyst accomplished the said condensation reaction within 15–30 min at room temperature conditions. All our synthesized compounds showed stronger affinities against Mycobacterium tb and bacterial targets, especially towards 1d7u, than the standard drug ciprofloxacin. One of our compounds retained a lower toxicity (electrophilicity index (ω) 3.1304), low chemical hardness (η: 2.1740), and high softness (S: 0.4600). In the realm of the development of more potent, effective, and safe antituberculosis agents with an effective greener synthesis, our current study would provide more insights on potent analogues containing hydrazine motifs in them

Mini-Review of the Importance of Hydrazides and Their Derivatives—Synthesis and Biological Activity

Organic acid hydrazides include a vast group of organic derivatives of hydrazines containing the active functional group (-C(=O)NHNH2). Acid hydrazones were important bidentate ligands and show keto-enol (amido-iminol) tautomerism. They usually exist in keto form in the solid-state while in equilibrium between keto and enol forms in solution state. Such hydrazones were synthesized in the laboratory by heating substituted hydrazides or hydrazines with corresponding aldehydes or ketones in different organic solvents such as ethanol, methanol, butanol, tetrahydrofuran, etc., and some cases with the ethanol-glacial acetic acid or acetic acid alone. Hydrozones are very important intermediates for the synthesis of heterocyclic compounds and also have different biological activities. The organic chemist would have more interest in the synthesis of acid hydrazides and their derivatives because of their properties. These derivatives having wide applications as chemical preservers for plants, drugs, for manufacturing polymers, glues, etc., in industry and many other purposes. These acid hydrazides and their derivatives were found to be useful synthons for various heterocyclic five, six or seven-membered rings with one or more heteroatoms that were exhibited great biological, pharmacological and industrial applications. This paper will present a review of the chemistry and pharmacological potentials of hydrazide-hydrazones. The various synthetic routes for hydrazone, as well as antibacterial, antifungal and antiviral potentials, have been elaborated in brief

The anti-SARS-CoV-2 activity of novel 9, 10-dihydrophenanthrene derivatives: an insight into molecular docking, ADMET analysis, and molecular dynamics simulation

Originating in Wuhan, the COVID-19 pandemic wave has had a profound impact on the global healthcare system. In this study, we used a 2D QSAR technique, ADMET analysis, molecular docking, and dynamic simulations to sort and evaluate the performance of thirty-nine bioactive analogues of 9,10-dihydrophenanthrene. The primary goal of the study is to use computational approaches to create a greater variety of structural references for the creation of more potent SARS-CoV-2 3Clpro inhibitors. This strategy is to speed up the process of finding active chemicals. Molecular descriptors were calculated using ‘PaDEL’ and ‘ChemDes’ software, and then redundant and non-significant descriptors were eliminated by a module in ‘QSARINS ver. 2.2.2’. Subsequently, two statistically robust QSAR models were developed by applying multiple linear regression (MLR) methods. The correlation coefficients obtained by the two models are 0.89 and 0.82, respectively. These models were then subjected to internal and external validation tests, Y-randomization, and applicability domain analysis. The best model developed is applied to designate new molecules with good inhibitory activity values against severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). We also examined various pharmacokinetic properties using ADMET analysis. Then, through molecular docking simulations, we used the crystal structure of the main protease of SARS-CoV-2 (3CLpro/Mpro) in a complex with the covalent inhibitor ''Narlaprevir'' (PDB ID: 7JYC). We also supported our molecular docking predictions with an extended molecular dynamics simulation of a docked ligand-protein complex. We hope that the results obtained in this study can be used as good anti-SARS-CoV-2 inhibitors

Development of Orally Active Anti-Inflammatory Agents: In Vivo and In Silico Analysis of Naphthalene-Chalcone Derivatives Based on 2-Acetyl-6-Methoxy Naphthalene

Chalcone compounds are reported to have diverse biological activities such as antiviral, antimicrobial, antimalarial, antitumor, antifungal, anticancer, and so forth. Herewith, we wish to report the in-vivo anti-inflammatory activities of previously synthesized naphthalene-chalcone hybrids from 2-Acetyl-6-Methoxy Naphthalene derivatives (C1-C25). All synthesized chalcones (C1-C25) were thoroughly characterized with standard spectroscopic techniques and tested for their in-vivo anti-inflammatory activities. The currently employed in-silico docking methodology uses the ‘Molegro Virtual Docker’ as a docking tool and target proteins as COX-1 (PDB ID: 1EQH) and COX-2 (PDB ID: 1PXX). Molecular docking analysis of chalcones (C1-C25) suggested that compound C-24 exhibited b docking score of -117.495 kcal/mol than the standard flurbiprofen -115.259 kcal/mol on COX-1 target. To understand more about pharmacokinetics aspects, we predicted theoretical ADME properties using ‘QikProp, 2022’ and found that all compounds were exhibited acceptable pharmacokinetic properties

An efficient one-pot multicomponent, Amberlite IR120(H) catalyzed microwave-assisted synthesis of 1,2,4,5-tetrasubstituted-1<i>H</i>-imidazoles: Plausible mechanism and antibacterial evaluation

The present study describes an efficient and convenient one-pot multicomponent, microwave-assisted synthesis of polysubstituted-1H-imidazoles in good yields under mild reaction conditions. The procedure uses inexpensive, nontoxic, and reusable Amberlite IR120(H) as a catalyst. The new method exhibits a broad tolerance for diverse structural moieties, thereby demonstrating the robustness and applicability of the synthetic method. Further synthesized polysubstituted-1H-imidazoles exhibited moderate to good activity against bacterial strains under study.</p