Insight Study For Repurposing Of Certain Anti‐Inflammatory Drugs Based On Aspirin and Salicylic Acid Scaffolds For The Treatment of Cancer as CDKs Inhibitors: Cheminformatics and Anticancer Studies

ChemistrySelect, Год журнала: 2025, Номер 10(15)

Опубликована: Апрель 1, 2025

Abstract The highly increased and global mortality due to cancer has created an urgent need discover promising targets for its treatment. Where drug repurposing was considered as attractive approach that can facilitate the lead generation optimization phases of discovery by existing agents target diseases other than their primary uses. Cheminformatics studies represented in molecular docking well dynamic simulation salicylic acid / aspirin analogues sulindac indomethacin anti‐inflammatory drugs were carried out be used cyclin‐dependent kinases (CDKs) namely CDK2, CDK6, CDK12 inhibitors. Sulindac displayed best binding ligand all receptors. CDKs inhibition effects three sulindac, anthranilic demonstrated good inhibitory activity against ranging from 0.48 1.78 µM. Likewise, cytotoxicity revealed potent anticancer 0.155 1.278 µM cell lines: HCT‐116, MCF‐7, HeLa cells. As a result, this technique saves lot time money order new agents.

Язык: Английский

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Novel Benzenesulfonamide Derivatives Linked to Diaryl Pyrazole Tail as Potential Carbonic Anhydrase II/VII Inhibitors with Anti-epileptic Activity

European Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown, С. 117619 - 117619

Опубликована: Апрель 1, 2025

Язык: Английский

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Exploring anticancer properties of new triazole-linked benzenesulfonamide derivatives against colorectal carcinoma: Synthesis, cytotoxicity, and in silico insights

Bioorganic & Medicinal Chemistry, Год журнала: 2025, Номер 119, С. 118060 - 118060

Опубликована: Янв. 5, 2025

Язык: Английский

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Incorporation of human β-defensin-1 into immunoliposomes to facilitate targeted autophagy therapy of colon carcinoma

World Journal of Clinical Oncology, Год журнала: 2025, Номер 16(3)

Опубликована: Янв. 20, 2025

Based on the discovery that human β-defensin-1 (hBD-1) triggers autophagy in colon cancer cells and inhibits proliferation, we proposed consideration of its druggability. As a protein, stability, targetability bioavailability must be improved. Compared with traditional medicinal chemistry technology, nanotechnology is more economical for increasing druggability hBD-1 can readily scaled up. Here, propose an immunoliposome system containing to improve stability bioavailability. To enhance targetability, anti-epidermal growth factor receptor (EGFR) antibodies were conjugated liposomal bilayer produce immunoliposomes target EGFR, which highly expressed cells. Although studies are needed support clinical trials large-scale manufacturing, these have great potential as therapeutics. Thus, suitable nanovesicles hBD-1; however, additional basic translational research systems warranted.

Язык: Английский

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New amidrazone analogs as multi-kinase inhibitors: in-silico and biological investigation as an anticancer agent

Medicinal Chemistry Research, Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

Язык: Английский

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Synthesis and evaluation of carmofur analogs as antiproliferative agents, inhibitors to the main protease (Mpro) of SARS-CoV-2, and membrane rupture-inducing agents

Discover Chemistry., Год журнала: 2025, Номер 2(1)

Опубликована: Апрель 7, 2025

Язык: Английский

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Synthesis of Novel Isoindolinones: Carbonic Anhydrase Inhibition Profiles, Antioxidant Potential, Antimicrobial Effect, Cytotoxicity and Anticancer Activity

Journal of Biochemical and Molecular Toxicology, Год журнала: 2025, Номер 39(4)

Опубликована: Апрель 1, 2025

ABSTRACT An efficient one‐pot method has been developed for synthesizing novel isoindolinone derivatives from 2‐benzoylbenzoic acid using chlorosulfonyl isocyanate and alcohols. This reaction occurs under mild, metal‐free conditions, rendering it a sustainable effective approach synthesis. The inhibitory potential of the synthesized compounds against human carbonic anhydrase (hCA) I II isozymes was evaluated compared with standard inhibitor, acetazolamide (AAZ). Additionally, their antimicrobial antioxidant activities were assessed various bioanalytical methods, results benchmarked reference compounds. Furthermore, cytotoxicity anticancer activity investigated in L929 A549 cell lines via WST‐1 assay following 24 h exposure. Among derivatives, 2c 2f exhibited superior effects on hCA to AAZ, Ki values ranging 11.48 ± 4.18 16.09 4.14 nM 9.32 2.35 14.87 3.25 II. These findings indicate that have high affinity enzyme's active site, resulting more inhibition its catalytic activity. Compound 2e emerged as most promising candidate, demonstrating potent significant properties. None displayed cytotoxic healthy cells at tested concentrations. compound 2a dose‐dependent cells. suggest particularly , hold substantial further pharmaceutical development multifunctional bioactive agents.

Язык: Английский

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Development of new anticancer thiadiazole-sulfonamides as dual EGFR/carbonic anhydrase inhibitors

Future Medicinal Chemistry, Год журнала: 2025, Номер unknown, С. 1 - 16

Опубликована: Май 8, 2025

Thiadiazole-sulfonamide derivatives were synthesized as dual inhibitors of epidermal growth factor receptor (EGFR) and carbonic anhydrase IX (CA-IX) to develop selective anticancer agents. Cytotoxicity was evaluated against MDA-MB-231 MCF-7 breast cancer cells, with selectivity tested on Vero cells. Enzymatic inhibition studies conducted EGFR CA-IX, using erlotinib acetazolamide reference drugs. Apoptosis assessed through gene expression analysis BAX/Bcl-2, caspase-8, caspase-9, alongside flow cytometry for apoptosis cell cycle analysis. Molecular docking 200 ns molecular dynamics (MD) simulations binding interactions. Density Functional Theory (DFT) calculations in silico ADMET predictions stability, electronic properties, safety. Compound 14 exhibited potent cytotoxicity (IC₅₀ = 5.78 μM, MDA-MB-231; 8.05 MCF-7) high 313.08 Vero). It inhibited 5.92 nM) CA-IX 63 nM), surpassing induction confirmed by a 13.97-fold increase caspase upregulation, G1-phase arrest. Computational analyses stable favorable represents promising EGFR/CA-IX inhibitor activity. Further vivo are warranted.

Язык: Английский

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Design and synthesis of new pyrazole hybrids linked to oxime and nitrate moieties as COX-2, EGFRL858R/T790M inhibitors and nitric oxide donors with dual anti-inflammatory/anti-proliferative activities

Bioorganic Chemistry, Год журнала: 2025, Номер 161, С. 108563 - 108563

Опубликована: Май 9, 2025

Язык: Английский

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Novel pyrazole carboxylate derivatives as lonazolac bioisosteres with selective COX-2 inhibition: design, synthesis and anti-inflammatory activity

Molecular Diversity, Год журнала: 2025, Номер unknown

Опубликована: Май 22, 2025

Abstract Two novel series of di-aryl/tri-aryl substituted pyrazole ester derivatives 15a-h and 19a-d were designed, synthesized as non-acidic lonazolac analogs tested for its COX-2, 5-LOX, 15-LOX, iNOS , pro-inflammatory cytokines TNF-α PGE2 inhibitory activities. All the compounds showed excellent COX-2 activity (IC 50 = 0.059–3.89 μM), compared to that celecoxib 0.22 where 15c, 15d, 15 h 19d found be most potent showing selectivity index in range (S.I. 28.56–98.71) 13.65). Moreover, four outstanding 5-LOX 15-LOX activities 0.24–0.81, 0.20–2.2 respectively, zileuton IC 1.52 0.54, respectively). Further investigation anti-inflammatory mechanistic study revealed these exhibited comparable (LPS-induced cytokines) 0.77–1.20 μM 0.28–0.52 respectively) when 0.87 0.38 reference drug using lipopolysaccharide-activated RAW 264.7 macrophages. Based on advanced against LPS-induced mediators (TNF-α PGE2), inducible nitric oxide synthase (iNOS) inhibition assay was carried out. Remarkably, higher potency with lower (0.41–0.61 µM) (0.48 µM). Prior vivo screening, cytotoxicity testing performed ascertain safe non-toxic concentrations each compound. Safe doses determined macrophages, moreover results more safer (less cytotoxic) (178.95–301.40 (148.90 In target reinforced vitro screening (ED 8.22–31.22 mg/kg, than 40.39 mg/kg). screened less ulcerogenic (ulcer indexes 1.22–3.93) 20.30) 3.02). silico docking ADME studies out order clarify interactions active enzymes their pharmacokinetic parameters.

Язык: Английский

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