Identification of some chalcone analogues as potential antileishmanial agents: An integrated in vitro and in silico evaluation

Osman, Marwa; Awad, Talal Ahmed; Shantier, Shaza W.; Garelnabi, Elrashied A. E.; Osman, Wadah; Mothana, Ramzi A.; Nasr, Fahd A.; Elhag, Rashid

doi:10.1016/j.arabjc.2022.103717

Cited by 14 publications

(4 citation statements)

References 52 publications

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“…Furthermore, it is in medicinal chemistry that chalcones are rightfully considered to have a privileged structure [ 5 ], since the chalcone core is present in a variety of important bioactive compounds with a broad spectrum of pharmacological activities, such as antimalarial, antibacterial, anticancer, anti-inflammatory, antiplasmodial, antioxidant, antifungal, antitubercular and antiviral agents [ 5 , 6 ]. Furthermore, recent reports have further indicated that chalcone derivatives ( Figure 1 ) may also be a promising pharmacophoric group against diseases caused by protozoa, including leishmaniasis [ 7 , 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Antileishmanial Activity of 4,8-Dimethoxynaphthalenyl Chalcones on Leishmania amazonensis

et al. 2022

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Leishmaniasis is a neglected tropical disease caused by Leishmania species. Available therapeutic options have several limitations. The drive to develop new, more potent, and selective antileishmanial agents is thus a major goal. Herein we report the synthesis and the biological activity evaluation against promastigote and amastigote forms of Leishmania amazonensis of nine 4,8-dimethoxynaphthalenyl chalcones. Compound ((E)-1-(4,8-dimethoxynaphthalen-1-yl)-3-(4-nitrophenyl)prop-2-en-1-one), 4f, was the most promising with an IC50 = 3.3 ± 0.34 μM (promastigotes), a low cytotoxicity profile (CC50 = 372.9 ± 0.04 μM), and a high selectivity index (SI = 112.6). Furthermore, 4f induced several morphological and ultrastructural changes in the free promastigote forms, loss of plasma membrane integrity, and increased reactive oxygen species (ROS). An in silico analysis of drug-likeness and ADME parameters suggested high oral bioavailability and intestinal absorption. Compound 4f reduced the number of infected macrophages and the number of amastigotes per macrophage, with an IC50 value of 18.5 ± 1.19 μM. Molecular docking studies with targets, ARG and TR, showed that compound 4f had more hydrogen bond interactions with the ARG enzyme, indicating a more stable protein-ligand binding. These results suggest that 4,8-dimethoxynaphthalenyl chalcones are worthy of further study as potential antileishmanial drugs.

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Section: Introductionmentioning

confidence: 99%

Antileishmanial Activity of 4,8-Dimethoxynaphthalenyl Chalcones on Leishmania amazonensis

et al. 2022

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“…The external validation coefficients Q 2 F1 (Equation ( 5)), Q 2 F2 (Equation ( 6)), and Q 2 F3 (Equation ( 7)) were used as indicators for evaluating the predictive ability of the model [27]. Their calculation formulas are shown in ( 3), ( 4), ( 5), (6), and (7), respectively.…”

Section: Quality Evaluation Of the Modelmentioning

confidence: 99%

“…Currently, QSPR models have been widely used in fields of medicinal chemistry, toxicology, biology, and materials, etc. [6][7][8][9][10][11][12]. The QSPR model, created using strong machine learning algorithms and integrated modeling software, can identify and optimize the experimental direction, reducing needless experimental measurement, shortening the experimental time, and lowering experiment expenses [13].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Antioxidant Properties and Molecular Design of Lubricant Antioxidants Based on QSPR Model

Liu,

Zhang,

et al. 2023

Lubricants

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Two quantitative structure–property relationship (QSPR) models of hindered phenolic antioxidants in lubricating oils were established to help guide the molecular structure design of antioxidants. Firstly, stepwise regression (SWR) was used to filter out essential molecular descriptors without autocorrelation, including electronic, topological, spatial, and structural descriptors, and multiple linear regression (MLR) was used to construct QSPR models based on the screened variables. The two models are statistically sound, with R2 values of 0.942 and 0.941, respectively. The models’ reliability was verified by the frontier molecular orbital energy gaps of the antioxidants. A hindered phenolic additive was designed based on the models. Its antioxidant property is calculated to be 20.9% and 11.0% higher than that of typical commercial antioxidants methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propionate and 2,2′-methylenebis(6-tert-butyl-4-methylphenol), respectively. The structure–property relationship of hindered phenolic antioxidants in lubricating oil obtained by computer-assisted analysis can not only predict the antioxidant properties of existing hindered phenolic additives but also provide theoretical basis and data support for the design or modification of lubricating oil additives with higher antioxidant properties.

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“…Chalcones have emerged as promising lead molecules in the fight against various parasitic infections, [27][28][29][30][31] including those caused by parasitic nematodes. [32,33] Hybrid benzimidazol-yl-chalcones and derivatives have demonstrated in vitro nematocidal activity against Haemonchus contortus.…”

Section: Introductionmentioning

confidence: 99%

Potent Anthelmintic Activity of Chalcones Synthesized by an Effective Green Approach

Turani,

Castro,

Vazzana

et al. 2024

ChemMedChem

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There is currently an urgent need for new anthelmintic agents due to increasing resistance to the limited available drugs. The chalcone scaffold is a privileged structure for developing new drugs and has been shown to exhibit potential antiparasitic properties. We synthesized a series of chalcones via Claisen‐Schmidt condensation, introducing a novel recoverable catalyst derived from biochar obtained from the pyrolysis of tree pruning waste. Employing microwave irradiation and a green solvent, this approach demonstrated significantly reduced reaction times and excellent compatibility with various functional groups. The result was the generation of a library of functionalized chalcones, exhibiting exclusive (E)‐selectivity and high to excellent yields. The chalcone derivatives were evaluated on the free‐living nematode Caenorhabditis elegans. The chalcone scaffold, along with two derivatives incorporating a methoxy substituent in either ring, caused a concentration‐dependent decrease of worm motility, revealing potent anthelmintic activity and spastic paralysis not mediated by the nematode levamisole‐sensitive nicotinic receptor. The combination of both methoxy groups in the chalcone scaffold resulted in a less potent compound causing worm hypermotility at the short term, indicating a distinct molecular mechanism. Through the identification of promising drug candidates, this work addresses the demand for new anthelmintic drugs while promoting sustainable chemistry.

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Identification of some chalcone analogues as potential antileishmanial agents: An integrated in vitro and in silico evaluation

Cited by 14 publications

References 52 publications

Antileishmanial Activity of 4,8-Dimethoxynaphthalenyl Chalcones on Leishmania amazonensis

Antileishmanial Activity of 4,8-Dimethoxynaphthalenyl Chalcones on Leishmania amazonensis

Evaluation of Antioxidant Properties and Molecular Design of Lubricant Antioxidants Based on QSPR Model

Potent Anthelmintic Activity of Chalcones Synthesized by an Effective Green Approach

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