Exploring the Potential Biological Activities of Pyrazole-Based Schiff Bases as Anti-Diabetic, Anti-Alzheimer’s, Anti-Inflammatory, and Cytotoxic Agents: In Vitro Studies with Computational Predictions

Pharmaceuticals, Год журнала: 2024, Номер 17(5), С. 655 - 655

Опубликована: Май 17, 2024

In this innovative research, we aim to reveal pyrazole-based Schiff bases as new multi-target agents. context, re-synthesized three sets of bases, 5a–f, 6a–f, and 7a–f, evaluate their biological applications. The data from in vitro assays (including antioxidant scavenging activities, anti-diabetes, anti-Alzheimer’s, anti-inflammatory properties) the 7a–f showed that six 5a, 5d, 5e, 5f, 7a, 7f possess highest properties among compounds evaluated. cytotoxicity against lung (A549) colon (Caco-2) human cancer types, well normal (WI-38) cell lines, was investigation demonstrated 7a are active cells, while two 5e exhibited towards cells. Additionally, enzymatic activities caspase-3 Bcl-2 were Furthermore, assessed silico absorption, distribution, metabolism, toxicity (ADMT) more potent bases. After modifying structures plan further extend studies future.

Язык: Английский

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Explore new quinoxaline pharmacophore tethered sulfonamide fragments as in vitro α‐glucosidase, α‐amylase, and acetylcholinesterase inhibitors with ADMET and molecular modeling simulation

Drug Development Research, Год журнала: 2024, Номер 85(4)

Опубликована: Июнь 1, 2024

Abstract A new series of quinoxaline‐sulfonamide derivatives 3 – 12 were synthesized using fragment‐based drug design by reaction quinoxaline sulfonyl chloride (QSC) with different amines and hydrazines. The evaluated for antidiabetic anti‐Alzheimer's potential against α‐glucosidase, α‐amylase, acetylcholinesterase enzymes. These showed good to moderate potency α‐amylase α‐glucosidase inhibitory percentages between 24.34 ± 0.01%–63.09 0.02% 28.95 0.04%–75.36 0.01%, respectively. Surprisingly, bis ‐sulfonamide derivative 4 revealed the most potent activity 75.36 0.01% 63.09 α ‐glucosidase compared acarbose (IP = 57.79 67.33 0.01%), Moreover, exhibited as a minute decline from compound 44.93 38.95 0.01%. Additionally, in vitro designed weak activity. Still, sulfonamide‐quinoxaline emerged active member percentage 41.92 donepezil 67.27 0.60%). DFT calculations, docking simulation, target prediction, ADMET analysis performed discussed detail.

Язык: Английский

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Bioactive Fused Pyrazoles Inspired by the Adaptability of 5-Aminopyrazole Derivatives: Recent Review

Molecules, Год журнала: 2025, Номер 30(2), С. 366 - 366

Опубликована: Янв. 17, 2025

Heterocyclic compounds, especially those containing the pyrazole moiety, are highly significant in organic chemistry and possess remarkable diverse biological properties. The 5-aminopyrazole derivatives key starting materials for synthesis of numerous bioactive compounds such as pyrazolopyridine, pyrazolopyrimidine, pyrazoloquinazoline, pyrazolotriazine derivatives. Many inspired by a wide spectrum activities medicinal applications antioxidants, anticancer agents, enzyme inhibitors, antimicrobials, anti-tuberculosis activities. This review summarizes recently reported methods fused pyrazole-based based on within last 5 years (2020 to present). One important goals this is illustrate future strategies design, development, utilization products potent drugs.

Язык: Английский

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In Vitro Enzymatic and Computational Assessments of Pyrazole–Isatin and Pyrazole–Indole Conjugates as Anti-Diabetic, Anti-Arthritic, and Anti-Inflammatory Agents

Pharmaceutics, Год журнала: 2025, Номер 17(3), С. 293 - 293

Опубликована: Фев. 23, 2025

Background/Objectives: Recently, the prevalence of diseases such as diabetes, arthritis, and inflammatory diseases, along with their complications, has become a significant health problem. This is in addition to various biomedical applications pyrazole, isatin, indole derivatives. Accordingly, cooperation will continue between chemistry scientists, pharmaceutical human doctors produce hybrid compounds from pyrazole isatin or possessing biological activities anti-diabetic, anti-arthritic, anti-inflammatory agents. Methods: The two series pyrazole–isatin conjugates 12a–h pyrazole–indole 14a–d were prepared our previous works via direct reaction 5-amino-pyrazoles 10a–d N-alkyl 11a,b, 1H-indole-3-carbaldehyde (13), respectively, using previously reported procedure. potential agents assessed through estimated inhibition percentage (%) median inhibitory concentrations (IC50) methods described literature. Further, computational assessments toxic doses (the lethal dose, LD50), toxicity classes, drug-likeness model scores (DLMS), molecular lipophilicity (MLP) maps, polar surface area (PSA) topological (TPSA) values predicted available free websites. Results: vitro enzymatic assessment results showed that conjugate 14b possesses powerful against (i) α-amylase (% = 65.74 ± 0.23, IC50 4.21 0.03 µg/mL) α-glucosidase 55.49 2.76 0.01 µg/mL); (ii) protein denaturation enzyme 49.30 0.17) proteinase 46.55 an value 6.77 µg/mL; (iii) COX-1, COX-2, 5-LOX enzymes 5.44 0.03, 5.37 0.04, 7.52 which almost close indomethacin zileuton drugs. Also, lipophilic properties thus can cross cell membranes, effective for treatment; all possess TPSA more than 140 Å2 good intestinal absorption. Conclusions: synthesized works. these concluded studied results. In future, research team present vitro, vivo biological, hopefully obtain effectual anti-inflammatory.

Язык: Английский

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Investigations of In Vitro Anti-Acetylcholinesterase, Anti-Diabetic, Anti-Inflammatory, and Anti-Cancer Efficacy of Garden Cress (Lepidium sativum Linn.) Seed Extracts, as Well as In Vivo Biochemical and Hematological Assays

Pharmaceutics, Год журнала: 2025, Номер 17(4), С. 446 - 446

Опубликована: Март 31, 2025

Background/Objectives: The current research was designed to quantify the active phyto-constituents and investigate in vitro biological efficiency of different garden cress (Lepidium sativum Linn.) seed extracts against chronic diseases as well vivo toxicities that may be induced mice upon administration each extract at both studied therapeutic doses. Methods: L. extracts, such methanolic, aqueous, acetone, ethyl acetate assessed. inhibition percentage (%) median inhibitory concentration (IC50) values were estimated acetylcholinesterase enzyme, diabetes mellitus (α-amylase α-glucosidase enzymes), inflammation (cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) enzymes). Additionally, HepG-2, Caco-2, A549 cells assessed using 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Moreover, might hematological (using an automatic blood analyzer) biochemical levels evaluated. Results: It found methanolic possessed highest activities compared other extracts. 51.34, 54.35, 44.10, 43.48, 40.78% acetylcholinesterase, α-amylase, α-glucosidase, protein denaturation, proteinase enzymes, respectively. also exhibited effect COX-1 (55.05%), COX-2 (57.30%), 5-LOX (50.15%) enzymes. possesses cytotoxic activity cells, with IC50 52.27, 40.73, 37.95 μg/mL, lethal doses (LD50) showed safer when administered orally, followed by aqueous then extract. acetone no alterations orally two (1/10 1/20 LD50) control. Conclusions: This study concluded than In future, efficacy will evaluated, elucidation its mechanism diseases.

Язык: Английский

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Synthesis, antimicrobial and antioxidant activities of some new pyrazolo[1,5-a]pyrimidine and imidazo[1,2-b]pyrazole derivatives based isoxazole

Synthetic Communications, Год журнала: 2023, Номер 53(17), С. 1451 - 1467

Опубликована: Июль 9, 2023

A new set of pyrazolo[1,5-a]pyrimidines 5–8 and imidazo[1,2-b]pyrazoles 9–11 incorporating isoxazole as pharmacologically attractive cores were synthesized starting with aminopyrazole derivative 4. Moreover, the treatment arylidine 3 hydroxylamine hydrochloride nucleophilic reagent afforded 12. All target derivatives assessed in vitro antimicrobial candidates against six strains (three Gram + ve Bacteria three -ve Bacteria) two fungi. Target compounds 4, 5, 6, 9 10 illustrated potent activity some pathogens compared to reference drug Ampicillin minimum inhibitory concentration (MIC) values cases less than other represented moderate week inactive a compound 8. Compounds 6 showed Finally, antioxidant activities performed for most promising targets (except 3a,b 8) which displayed very strong activities.

Язык: Английский

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Efficient synthesis and molecular docking of new organoselenium and organosulphur compounds as dual inhibitors for the therapy of Alzheimer's disease as well as Diabetes Mellitus

Journal of Molecular Structure, Год журнала: 2024, Номер unknown, С. 140606 - 140606

Опубликована: Ноя. 1, 2024

Язык: Английский

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