Structural modification strategies of triazoles in anticancer drug development

European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 275, С. 116578 - 116578

Опубликована: Июнь 13, 2024

Язык: Английский

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New 1,2,4-triazole based eugenol derivatives as antiCOX-2 and anticancer agents

Journal of Umm Al-Qura University for Applied Sciences, Год журнала: 2024, Номер 10(3), С. 555 - 566

Опубликована: Фев. 19, 2024

Abstract Due to chronic inflammation, elevated cyclooxygenase (COX-2) level leads tumorigenesis, proliferation, invasion, angiogenesis and metastasis. Therefore, suppression of COX-2 enzyme is a fascinating approach in cancer treatment. In the present study, natural product eugenol was modified develop new 1,2,4-triazole derivatives as antiCOX-2 antiproliferative agents. The structures newly prepared were established using sophisticated analytical techniques. result showed compound 10 be equipotent doxorubicin towards MDA-MB 231 PC-3 cells with IC 50 1.42 5.69 μM, respectively potent inhibitor 0.28 μM. Compound also non carcinogenic, mutagenic good drug likeness property depicted by silico physicochemical pharmacokinetic studies. docking results against protein highest binding energy for which found consistent cytoxicity results. conclusion, could harness cell proliferation promising candidate therapy.

Язык: Английский

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Fractionation and Characterization of Triterpenoids from Vaccinium vitis-idaea L. Cuticular Waxes and Their Potential as Anticancer Agents

Antioxidants, Год журнала: 2023, Номер 12(2), С. 465 - 465

Опубликована: Фев. 12, 2023

Fruit and leaf cuticular waxes are valuable source materials for the isolation of triterpenoids that can be applied as natural antioxidants anticancer agents. The present study aimed at semi-preparative fractionation from wax extracts Vaccinium vitis-idaea L. (lingonberry) leaves fruits evaluation their cytotoxic potential. Qualitative quantitative characterization obtained triterpenoid fractions was performed using HPLC-PDA method, followed by complementary analysis GC-MS. For each fraction, activities towards human colon adenocarcinoma cell line (HT-29), malignant melanoma (IGR39), clear renal carcinoma (CaKi-1), normal endothelial cells (EC) were determined MTT assay. Furthermore, effect most promising samples on cancer spheroid growth viability examined. This allowed us to confirm particular mixtures lingonberry may possess stronger than crude unpurified extracts. Fractions containing acids plus fernenol, complexes oleanolic:ursolic acids, erythrodiol:uvaol found potent therapeutic candidates in management diseases. specificity fruits, leading different purity potential counterpart fractions, also enclosed. These findings contribute profitable utilization provide considerable insights into effects pharmacological interactions.

Язык: Английский

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3D tumor spheroids: morphological alterations a yardstick to anti-cancer drug response

In vitro models, Год журнала: 2023, Номер 2(6), С. 219 - 248

Опубликована: Сен. 20, 2023

Tumor spheroids are one of the well-characterized 3D culture systems bearing close resemblance to physiological tissue organization and complexity avascular solid tumor stage with hypoxic core. They hold a wide-spread application in field pharmaceutical science anti-cancer drug research. However, difficulty determining optimal technique for generation uniform size shape, evaluation experimental outputs, or mass production often limits their usage research high-throughput screening. In recent times, several studies have demonstrated various simple techniques generating uniform-size spheroids, including hanging drop (HD), liquid overlay (LOT), microfluidic approaches. Morphological alterations apart from biochemical assays, staining suitably employed outcomes within spheroid models. response effective treatment such as reduced size, loss compactness integrity smooth surface, highly reliable. These can significantly reduce need assays techniques, resulting both time cost savings. The present article specifically covers variety available procedures generation. For practical applicability, we supplemented our review study glioblastoma U87 using HD LOT methods. Additionally, also incorporated outcome doxorubicin on morphology.

Язык: Английский

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The Effect of 4-(Dimethylamino)phenyl-5-oxopyrrolidines on Breast and Pancreatic Cancer Cell Colony Formation, Migration, and Growth of Tumor Spheroids

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(3), С. 1834 - 1834

Опубликована: Фев. 2, 2024

A series of hydrazones, azoles, and azines bearing a 4-dimethylaminophenyl-5-oxopyrrolidine scaffold was synthesized. Their cytotoxic effect against human pancreatic carcinoma Panc-1 triple-negative breast cancer MDA-MB-231 cell lines established by MTT assay. Pyrrolidinone derivatives 3c 3d, with incorporated 5-chloro 5-methylbenzimidazole fragments; hydrazone 5k 5-nitrothien-2-yl substitution; 5l naphth-1-yl fragment in the structure significantly decreased viability both lines. Compounds showed highest selectivity, especially line. The EC50 values most active compound MDA-MB231 line 7.3 ± 0.4 μM, which were slightly higher (10.2 2.6 μM). Four selected pyrrolidone relatively high activity clonogenic Compound cultures, it completely disturbed colony growth at 1 2 μM strong on formation, μM. compounds did not show an inhibitory migration ‘wound-healing’ 3d efficiently inhibited spheroids reduced spheroids. Considering these different activities biological assays, pyrrolidinone could be further tested to better understand structure–activity relationship their mechanism action.

Язык: Английский

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Synthesis, biological evaluation and in silico studies of clopidogrel based new 1,2,4-triazole-3-thione derivatives as DNA methyltransferase inhibitors on prostate cancer cells

Journal of Molecular Structure, Год журнала: 2025, Номер unknown, С. 142081 - 142081

Опубликована: Март 1, 2025

Язык: Английский

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Novel 5-Oxopyrrolidine-3-carbohydrazides as Potent Protein Kinase Inhibitors: Synthesis, Anticancer Evaluation, and Molecular Modeling

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3162 - 3162

Опубликована: Март 29, 2025

A series of novel hydrazones bearing diphenylamine and 5-oxopyrrolidine moieties, along with benzene naphthalene rings substituted hydroxy, alkoxy, or carboxylic groups, were synthesized. Their anticancer activity was evaluated in vitro using both 2D (MTT ‘wound healing’ assays) 3D (cell spheroid) models against human melanoma IGR39 cells, the triple-negative breast cancer cell line MDA-MB-231, pancreatic carcinoma Panc-1 line. Compounds 8 (2-hydroxybenzylidene derivative) 12 (2-hydroxynaphthalenylmethylene demonstrated highest cytotoxicity assays, while compounds 4 (2,5-dimethoxybenzylidene 6 (2,4,6-trimethoxybenzylidene most effective at inhibiting migration. Notably, all exhibited lower a monolayer, but effects on spheroid viability comparable across tested lines. Molecular docking studies active suggested that these may act as multikinase inhibitors. In particular, 2-hydroxynaphthalenylmethylene derivative showed high binding affinity values (−11.174 −11.471 kcal/mol) to sites two key protein kinases—a non-receptor TK (SCR) STPK (BRAF)—simultaneously.

Язык: Английский

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Anticancer properties of Cirsium vulgare (Savi) ten. Dry extracts from different plant parts and phenological stages of Raw material collection

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Апрель 9, 2025

This study explores the anticancer potential of Cirsium vulgare dry extracts in human colorectal adenocarcinoma (HT-29) and gastric carcinoma (KATO III) cell lines using both traditional 2D monolayer models advanced 3D spheroid systems. Cell viability was assessed via MTT assay, while influence on migration evaluated a wound-healing assay. In cultures, extract activity further examined through magnetic bioprinting to monitor growth dynamics, cells spheroids by WST-1 Among tested extracts, those derived from C. inflorescences (U1) roots (U6, U7, U8, U9) demonstrated higher activity. The inflorescence exhibited highest cytotoxic against cancer lines, root-derived particularly showed potent suppression HT-29 migration, achieving most significant reduction wound closure after 36 h (p < 0.05) at concentration 0.2 mg/mL. models, U1 U8 reduced 53.3-77.9% 56.7-81.5%, respectively, emerged as effective inhibitor growth, reducing diameter 7-10%, compared untreated controls. These findings underscore promising highlighting their innovative therapeutic candidates for treating cancers. Further investigations are warranted refine application oncological research.

Язык: Английский

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Synthesis and In Vitro Evaluation as Potential Anticancer and Antioxidant Agents of Diphenylamine-Pyrrolidin-2-one-Hydrazone Derivatives

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(23), С. 16804 - 16804

Опубликована: Ноя. 27, 2023

The title compounds were synthesized by the reaction of 5-oxo-1-(4-(phenylamino)phenyl)pyrrolidine-3-carbohydrazide with various aldehydes bearing aromatic and heterocyclic moieties acetophenones, their cytotoxicity was tested via MTT assay against human triple-negative breast cancer MDA-MB-231, melanoma IGR39, pancreatic carcinoma Panc-1, prostate cell line PPC-1. Furthermore, selectivity towards cells compared to fibroblasts also investigated. Four identified as most promising anticancer agents out a series pyrrolidinone-hydrazone derivatives diphenylamine moiety. These selective PPC-1 lines EC50 values in range 2.5-20.2 µM these lines. In general, less active MDA-MB-231 line, none them showed an inhibitory effect on migration cells. 'wound healing' assay, N'-((5-nitrothiophen-2-yl)methylene)-5-oxo-1-(4-(phenylamino)phenyl)pyrrolidine-3-carbohydrazide derivative that could be further developed antimetastatic agent. N'-(5-chloro- N'-(3,4-dichlorobenzylidene)-5-oxo-1-(4-(phenylamino)phenyl)pyrrolidine-3-carbohydrazides efficiently reduced viability IGR39 spheroids, while there no investigated 3D cultures. Antioxidant activity determined FRAP N'-(1-(4-aminophenyl)ethylidene)-5-oxo-1-(4-(phenylamino)phenyl)pyrrolidine-3-carbohydrazide 1.2 times higher than protocatechuic acid.

Язык: Английский

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Design, synthesis, and antiproliferative activities of novel substitutedhydrazone/triazolo-linked quinazoline derivatives

Journal of Molecular Structure, Год журнала: 2024, Номер 1306, С. 137822 - 137822

Опубликована: Фев. 17, 2024

Язык: Английский

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