Mechanochemical Synthesis and Molecular Docking Studies of New Azines Bearing Indole as Anticancer Agents

Molecules, Год журнала: 2023, Номер 28(9), С. 3869 - 3869

Опубликована: Май 4, 2023

The development of new approaches for the synthesis bioactive heterocyclic derivatives is utmost importance pharmaceutical industry. In this regard, present study reports green benzaldazine and ketazine via condensation various carbonyl compounds (aldehydes ketones with 3-(1-hydrazineylideneethyl)-1H-indole using grinding method one drop acetic acid). Various spectroscopic techniques were used to identify structures synthesized derivatives. Furthermore, anticancer activities reported azine evaluated against colon, hepatocellular, breast carcinoma cell lines MTT technique doxorubicin as a reference medication. findings suggested that exhibited potential anti-tumor toward different lines. For example, 3c, 3d, 3h, 9, 13 interesting activity an IC50 value 4.27–8.15 µM towards HCT-116 line compared (IC50 = 5.23 ± 0.29 µM). addition, 11, showed excellent cytotoxic 4.09–9.05 µM) HePG-2 4.50 0.20 µM), demonstrated high potency 6.19–8.39 (MCF-7) drug 4.17 molecular interactions between 3a-h, 7, 13, CDK-5 enzyme (PDB ID: 3IG7) studied further docking indicating level support experimental results. drug-likeness analysis indicated derivative 9 (binding affinity −8.34 kcal/mol) would have better pharmacokinetics, drug-likeness, oral bioavailability (−7.04 kcal/mol). These results along structure–activity relationship (SAR) will pave way design additional azines bearing indole activities.

Язык: Английский

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Synthesis, Biological Evaluation, and Molecular Docking of Novel Azolylhydrazonothiazoles as Potential Anticancer Agents

ACS Omega, Год журнала: 2023, Номер 8(37), С. 34044 - 34058

Опубликована: Сен. 5, 2023

A novel set of thiazolylhydrazonothiazoles bearing an indole moiety were synthesized by subjection reactions carbothioamide derivative and hydrazonoyl chlorides (or α-haloketones). The cytotoxicity the compounds was evaluated against colon carcinoma cell line (HCT-116), liver (HepG2), breast (MDA-MB-231), demonstrated encouraging activity. Furthermore, when representative products assessed for toxicity normal cells, minimal toxic effects observed, indicating their potential safety use in pharmacological studies. mechanism action tested products, as inhibitors epidermal growth factor receptor tyrosine kinase domain (EGFR TK) protein, suggested through docking studies that binding scores modes, comparison to a reference standard (W19), thus endorsing anticancer

Язык: Английский

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Synthesis, molecular docking study, and biological evaluation and of new thiadiazole and thiazole derivatives incorporating isoindoline-1,3-dione moiety as anticancer and antimicrobial agents

Results in Chemistry, Год журнала: 2024, Номер 7, С. 101375 - 101375

Опубликована: Янв. 1, 2024

To highlight the importance of thiazole and thiadiazole derivatives in progression cancer microbial treatments to aid drug design, we have synthesized a new series 1,3,4-thiadiazole 1,3-thiazole derivatives. These were created by two-step reaction process: initially, 2-(4-(2-bromoacetyl)phenyl)isoindoline-1,3-dione was reacted with potassium thiocyanate, then resulting thiocyanate intermediate coupled aryl diazonium salts produce iminothiadiazole served as crucial intermediates for further synthesizing range using different reagents. Additionally, treating 2-(4-(2-bromoacetyl) phenyl)isoindoline-1,3-dione thiourea resulted aminothiazole arenediazonium chloride form 5-arylazoaminothiazole All synthesised compounds characterised IR, 1H NMR 13C spectrum data, well physical data. The assessment on HCT-116 human colon cell line has yielded promising results. Specifically, 3a, 3b, 4b, 5b, 6b, 9b shown noteworthy efficacy, suggesting their potential anticancer agents. demonstrated greater potency compared standard drug, doxorubicin, highlighting significance treatment research. study assessed activity various newly against diverse microorganisms, including bacteria fungi. Notably, two these compounds, specifically 4b 7b, exhibited significant efficacy both gram-positive gram-negative bacteria, surpassing performance antibacterial reference agent. Furthermore, molecular docking products revealed interactions enzyme binding sites, aligning vitro findings. in-silico studies confirmed favourable oral bioavailability through ADME profiling.

Язык: Английский

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Design, synthesis, in vitro biological assessment and in silico molecular modeling study of thiazole-thiazolidinone derivatives as potent anti-cancer agents

Results in Chemistry, Год журнала: 2024, Номер 7, С. 101507 - 101507

Опубликована: Янв. 1, 2024

The current study addressed the synthesis of thiazole-based thiazolidinone derivatives (1–18) using stepwise reaction processes, and their structure was confirmed various characterization techniques such as 1HNMR, 13CNMR, HREI-MS. Furthermore, biological features these analogues anti-cancer drugs against human cancer cell lines (HCC78 H3122) were identified. Their inhibitory potentials determined half-maximal concentration (MIC50) in presence standard Tetrandrineb (IC50 = 10.70 ± 0.30 µM), respectively. Structure activity relationship (SAR) established for all synthesized scaffolds compared with standard, which 1 5.20 0.40 2 4.10 0.20 3 6.30 4 8.90 0.10 6 8.10 7 8.70 8 3.90 9 2.10 10 3.30 µM) 16 exhibited most influential activity. These compounds subsequently examined molecular docking experiments, evaluate binding interactions ligands enzyme active sites.

Язык: Английский

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Green Synthesis and Molecular Docking Study of Some New Thiazoles Using Terephthalohydrazide Chitosan Hydrogel as Ecofriendly Biopolymeric Catalyst

Catalysts, Год журнала: 2023, Номер 13(9), С. 1311 - 1311

Опубликована: Сен. 20, 2023

Terephthalohydrazide chitosan hydrogel (TCs) was prepared and investigated as an ecofriendly biopolymeric catalyst for synthesis of some novel thiazole thiadiazole derivatives. Thus, TCs used a promising basic biocatalyst preparation three new series thiazoles two thiadiazoles derivatives via reacting 2-(2-oxo-1,2-diphenylethylidene) hydrazine-1-carbothio-amide with various hydrazonoyl chlorides α-haloketones under mild ultrasonic irradiation. Also, their yield% estimated using in comparative study. The procedure being employed has the advantages reaction conditions, quick durations, high yields. It also benefits from catalyst’s capacity to be reused several times without significantly losing potency. chemical structures newly compounds were confirmed by IR, MS, 1H-NMR. Docking analyses synthesized compounds’ binding modes revealed scores against amino acids selected protein (PDB Code—1JIJ). SwissADME’s online tool is then analyze physiochemical pharmacokinetic characteristics most significant substances. majority showed zero violation Lipinski’s rule (Ro5).

Язык: Английский

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A green synthesis, DFT calculations, and molecular docking study of some new indeno[2,1-b]quinoxalines containing thiazole moiety

Journal of Molecular Structure, Год журнала: 2023, Номер 1292, С. 136044 - 136044

Опубликована: Июнь 16, 2023

Язык: Английский

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Design and synthesis of novel hybrids incorporating thiadiazole or thiazole-naphthalene: Anticancer assessment and molecular docking study

Results in Chemistry, Год журнала: 2024, Номер 7, С. 101475 - 101475

Опубликована: Янв. 1, 2024

To underscore the significance of thiazole and thiadiazole moieties in advancing cancer treatment support researchers drug design, we developed a novel series 1,3,4-thiadiazole 1,3-thiazole derivatives. These were synthesized by reacting 2-(naphthalen-1-ylmethylene)-N-phenylhydrazine-1-carbothioamide with hydrazonoyl halides α-halo-compounds. Spectroscopic data alternative syntheses confirmed structures. The growth-inhibitory potential against HepG2-1 liver cells was evaluated using MTT assay, revealing compounds 5c 15 IC50 values 0.53 ± 0.82 0.61 0.72 μM, respectively, demonstrating promising anticancer activity than doxorubicin (IC50 = 0.49 μM). Given high attrition rate development, computational approaches employed to mitigate risks associated poor pharmacokinetics safety. Molecular docking analyses illustrated binding interactions at enzymes' sites, consistent vitro studies, indicating as antitumor agents. In silico investigations affirmed ADMET profile's favorable oral bioavailability properties for compounds. findings highlight investigated ligands candidates further development medicines.

Язык: Английский

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Cyanauric Chloride as a key precursor and a core component for Three-Armed Triazolopyrimidines: Recent finding about SARs and docking analyses

Results in Chemistry, Год журнала: 2024, Номер 7, С. 101337 - 101337

Опубликована: Янв. 1, 2024

The s-triazine trichloride is a reactive compound and can be used as key intermediate for delivering polysubstituted triazines specially the three-armed ones. Therefore, this utilized here synthesis of multi-armed bearing various heterocyclic moieties. A group novel heterocycles with three arms pryrimidines fused triazoles linked to triazine core component are prepared from s-trichlorotriazine aminothiouracil which gave title pyrimidinthione arms. combination tris-pyrimidinthione versatile hydrazonoyl halides in basic medium afforded pyrimidine ring. structures compounds characterized by analytical spectroscopic tools. For discovering new antibiotics scaffolds, synthesized 1,2,4-triazoles were considered most recent findings about triazole derivatives' structure-activity relationships (SARs) included article. One promising issue results docking analyses some our compounds' binding modes that its scores against amino acids selected protein (PDB Code–3TTZ) effective. In study 7d (−10.1 kcal/mol) was also displayed highest score.

Язык: Английский

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Synthesis, computational and antimicrobial study of 2-(2-Hydrazinyl)thiazole derivatives

Journal of Molecular Structure, Год журнала: 2023, Номер 1300, С. 137096 - 137096

Опубликована: Ноя. 15, 2023

Язык: Английский

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Synthesis of the chromone‐thiosemicarbazone scaffold as promising α‐glucosidase inhibitors: An in vitro and in silico approach toward antidiabetic drug design

Archiv der Pharmazie, Год журнала: 2024, Номер unknown

Опубликована: Апрель 30, 2024

Abstract Diabetes is a serious metabolic disorder affecting individuals of all age groups and prevails globally due to the failure previous treatments. This study aims address most prevalent form type 2 diabetes mellitus (T2DM) by reporting on design, synthesis, in vitro as well silico evaluation chromone‐based thiosemicarbazones potential α‐glucosidase inhibitors. In experiments showed that tested compounds were significantly more potent than standard acarbose, with lead compound 3n exhibiting an IC 50 value 0.40 ± 0.02 μM, ~2183‐fold higher acarbose having 873.34 1.67 μM. A kinetic mechanism analysis demonstrated exhibited reversible inhibition α‐glucosidase. To gain deeper insights, molecular docking, pharmacokinetics, dynamics simulations conducted for investigation interactions, orientation, stability, conformation synthesized within active pocket

Язык: Английский

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