Indole clubbed 2,4‐thiazolidinedione linked 1,2,3‐triazole as a potent antimalarial and antibacterial agent against drug‐resistant strain and molecular modeling studies

Archiv der Pharmazie, Год журнала: 2024, Номер 357(4)

Опубликована: Янв. 21, 2024

Abstract In the face of escalating challenges microbial resistance strains, this study describes design and synthesis 5‐({1‐[(1 H ‐1,2,3‐triazol‐4‐yl)methyl]‐1 ‐indol‐3‐yl}methylene)thiazolidine‐2,4‐dione derivatives, which have demonstrated significant antimicrobial properties. Compared with minimum inhibitory concentrations (MIC) values ciprofloxacin on respective compounds 5a , 5d 5g 5l 5m exhibited potent antibacterial activity MIC ranging from 16 to 25 µM. Almost all synthesized showed lower compared standards against vancomycin‐resistant enterococcus methicillin‐resistant Staphylococcus aureus strains. Additionally, majority remarkable antifungal activity, Candida albicans Aspergillus niger as nystatin, griseofulvin, fluconazole. Furthermore, notable effects Plasmodium falciparum strain, having IC 50 1.31 2.79 μM standard quinine (2.71 μM). Cytotoxicity evaluation 5a–q SHSY‐5Y cells at up 100 μg/mL no adverse effects. Comparison control groups highlights their noncytotoxic characteristics. Molecular docking confirmed compound binding target active sites, stable protein–ligand complexes displaying drug‐like molecules. dynamics simulations revealed dynamic stability interactions. Rigorous tests molecular modeling unveil effectiveness drug‐resistant microbes, providing hope for new potential safety.

Язык: Английский

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Investigating the potential of thiazolyl carbohydrazides derivatives as anti-Candida albicans agents: An intuition from molecular modelling, pharmacokinetic evaluation, and molecular docking analysis

Chemical Physics Impact, Год журнала: 2023, Номер 7, С. 100275 - 100275

Опубликована: Июль 27, 2023

With increasing incidences of antifungal resistance, biofilm formation, and its predilection for vulnerable populations, Candida albicans have been reported to cause a wide range infections, from superficial skin irritations life-threatening systemic diseases. Therefore, understanding addressing the infections associated with has become an urgent imperative in realm global healthcare. As result, this study employed DFT calculations at DFT/ωB97XD/6–311++G (2d, 2p) level optimize geometric properties two compounds: (Z)-N'-(4-(4-bromophenyl)-3-(4-fluorophenyl)thiazol-2(3H)-ylidene)-2-(thiophen-2-yl)thiazole-5-carbohydrazide (4-FBC) (Z)-N'-(4-(4-bromophenyl)-3-(2-fluorophenyl)thiazol-2(3H)-ylidene)-2-(thiophen-2-yl)thiazole-5-carbohydrazide(2-FBC). Significantly, employing spectral analysis techniques such as FT-IR NMR, compounds were characterized identified. Additionally, (4-FBC 2-FBC) exhibited comparable reactivity stability, more promising potential water than gas phase. The Molecular Electrostatic Potential (MESP) density States (DOS) shed light on electrical characteristics intermolecular interactions occurring during chemical processes. Furthermore, natural bond orbital (NBO) provided insights into second-order perturbation energies presence intense interactions, evident order their concentrated interaction thus: 4-FBC_gas (668.34 kcal/mol) > 4-FBC _water (563.98 2-FBC _gas (978.64 Kcal/mol) 2-FBC_water (696.46 Kcal/mol). pharmacokinetics indicated favorable intestinal absorption, low distribution, cytotoxicity profiles, although required further optimization due slower clearance, enzyme immunotoxicity concerns. In addition, molecular docking revealed robust binding affinities significant conventional hydrogen bonds. optimal positions (best pose) complexes determined -8.7, -8.4, -8.3 kcal/mol, -8.6, -8.5, respectively, when interacting 4YDE, 3DRA, 1EAG. These findings provide strong evidence supporting pharmacological suitability effective choices inhibiting treating albicans.

Язык: Английский

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A synthetic approach towards drug modification: 2-hydroxy-1-naphthaldehyde based imine-zwitterion preparation, single-crystal study, Hirshfeld surface analysis, and computational investigation

RSC Advances, Год журнала: 2024, Номер 14(10), С. 6476 - 6493

Опубликована: Янв. 1, 2024

The current work is about the modification of primary amine functionalized drugs, pyrimethamine and 4-amino-

Язык: Английский

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Cs2CO3-promoted one-pot synthesis of novel tetrahydrobenzofuran-4(2H)-ones: In vitro antimicrobial, antimalarial activity and in silico docking study

Results in Chemistry, Год журнала: 2024, Номер 7, С. 101304 - 101304

Опубликована: Янв. 1, 2024

A diverse set of tetrahydrobenzofuran-4(2H)-one derivative 4(a-o) were synthesized using a one-pot treatment dimedone, 3-(1H-imidazol-1-yl)benzaldehyde, and different phenacyl bromide by utilizing cesium carbonate as cost-effective catalyst in acetonitrile under mild reaction condition. During the synthesis compounds, two carbon–carbon (C–C) bonds one carbon–oxygen (C–O) bond are formed. All compounds obtained with moderate to good yield. The underwent screening assess their antimicrobial antimalarial properties. Compounds 4 l (117 µM) 4d (145 exhibited highest potency against A. baumannii Car. Resistant P. aeruginosa comparison standard drug chloramphenicol (155 µM), respectively. Compound (234 displayed efficacy C. albicans than that drug, fluconazole (327 while 4f (1018 showed greater niger griseofulvin (1417 µM). In addition, all titled activity. Among them, (1.60 has falciparum quinine (2.71 Since compound exhibits strong antibacterial fungal action among synthetics, it shows remarkable binding affinities −8.5 kcal mol−1 −9.1

Язык: Английский

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Optimizing solar cell performance: Synthesis, structural, and optical analysis of novel quinolinopyranopyridopyrimidine (QPPP)

Journal of Photochemistry and Photobiology A Chemistry, Год журнала: 2025, Номер unknown, С. 116334 - 116334

Опубликована: Фев. 1, 2025

Язык: Английский

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Catalyst-free synthesis of imidazo[5,1-b]quinazolines and their antimicrobial activity

Journal of Molecular Structure, Год журнала: 2023, Номер 1285, С. 135467 - 135467

Опубликована: Март 30, 2023

Язык: Английский

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A green bio-organic catalyst (taurine) promoted one-pot synthesis of (R/S)-2-thioxo-3,4-dihydropyrimidine(TDHPM)-5-carboxanilides: chiral investigations using circular dichroism and validation by computational approaches

RSC Advances, Год журнала: 2024, Номер 14(13), С. 9300 - 9313

Опубликована: Янв. 1, 2024

Twenty-three new derivatives of ( R / S )-TDHPM-5-carboxanilide have been synthesized with up to 99% yield. All racemates were separated using chiral HPLC (Prep LC) which provided 99.99% purity. AC was determined circular dichroism spectra.

Язык: Английский

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Insights into microwave assisted synthesis of spiro-chromeno[2,3-d]pyrimidines using PEG-OSO3H catalyst: DFT study and their antiproliferative activity

Journal of Molecular Structure, Год журнала: 2023, Номер 1292, С. 136174 - 136174

Опубликована: Июль 7, 2023

Язык: Английский

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In silico exploration of acetic acid driven multicomponent synthesis: design, characterization, and antioxidant evaluation of spiroacridines and spiroquinolines

RSC Sustainability, Год журнала: 2024, Номер 2(4), С. 1128 - 1141

Опубликована: Янв. 1, 2024

A simple, rapid and efficient multicomponent synthesis of spiroacridines spiroquinolines was carried out under the influence acetic acid their antioxidant properties, DFT, docking in silico ADMET drug-likeness properties were explored.

Язык: Английский

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Asymmetric synthesis of enantiopure tetracyclic dispirooxindolopyrrolidine-piperidones via microwave-assisted multicomponent reaction: Crystallographic analysis, antimicrobial activity and in silico studies

Journal of Molecular Structure, Год журнала: 2024, Номер 1308, С. 138104 - 138104

Опубликована: Март 21, 2024

In an attempt towards the development of new antimicrobials, we synthesized by microwave-assisted multicomponent reaction (MCR) enantiopure (E,E)-3,5-bisarylidene-N-[(S)-(-)-methylbenzyl]-4-piperidones, isatin and α-amino esters a series optically active tetracyclic dispirooxindolopyrrolidine-piperidones. The beneficial promising features this protocol such as simple operational procedure, short time (10 min), high product yields (up to 97%) make it efficient eco-friendly approach offering powerful mean expand structural diversity spirooxindoles. This appears hugely advantageous for high-throughput screening processes in drug discovery research. addition, crystallographic parameters inter- intramolecular interactions occurring spiropyrrolidine-fused piperidone derivative 4g were examined through single-crystal XRD analysis allowing determine absolute configuration compound. preliminary biological assessment their antimicrobial activity indicates that most screened products display higher than standard reference drugs Ampicillin Griseofulvin. Some them exhibited good moderate against both bacteria fungi. silico molecular docking predictive ADMET studies spirocompounds carried out. Molecular confirmed binding efficacy candidates 4c 4l low score energy values establishment diverse bonding with site residues. Finally, profiling spiroheterocycles proved remarkable drug-like pharmacokinetic properties.

Язык: Английский

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