Matrix Metalloproteinases Inhibitors in Cancer Treatment: An Updated Review (2013–2023)

Molecules, Год журнала: 2023, Номер 28(14), С. 5567 - 5567

Опубликована: Июль 21, 2023

Matrix metalloproteinases (MMPs) are identifiable members of proteolytic enzymes that can degrade a wide range proteins in the extracellular matrix (ECM). MMPs be categorized into six groups based on their substrate specificity and structural differences: collagenases, gelatinases, stromelysins, matrilysins, metalloelastase, membrane-type MMPs. have been linked to variety biological processes, such as cell transformation carcinogenesis. Over time, evaluated for role cancer progression, migration, metastasis. Accordingly, various become attractive therapeutic targets anticancer drug development. The first generations broad-spectrum MMP inhibitors displayed effective inhibitory activities but failed clinical trials due poor selectivity. Thanks evolution X-ray crystallography, NMR analysis, homology modeling studies, it has possible characterize active sites and, consequently, develop more selective, second-generation inhibitors. In this review, we summarize computational synthesis approaches used development evaluation potential agents.

Язык: Английский

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Discovery of matrix metalloproteinase inhibitors as anti-skin photoaging agents

European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 267, С. 116152 - 116152

Опубликована: Янв. 14, 2024

Язык: Английский

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Synthesis, molecular modeling investigation, molecular dynamic and ADME prediction of some novel Mannich bases derived from 1,2,4-triazole, and assessment of their anticancer activity

Journal of Biomolecular Structure and Dynamics, Год журнала: 2023, Номер 42(21), С. 11916 - 11930

Опубликована: Окт. 15, 2023

AbstractA series of biologically active novel Mannich bases containing with a 1H-1,2,4-triazole-5-one ring were developed to evaluate the cytotoxic activity. For this purpose, synthesized Schiff Bases (S1-5) reacted formaldehyde and morpholine, which is secondary amine yield N-Mannich (M1-5) via reaction. The structures compounds determined structurally employing 1H/13C-NMR, IR elemental analysis. In study, we evaluated potential on human hypopharyngeal carcinoma FaDu cells. We found that compound (M3) possesses significant anticancer feature against cells might be further in vitro vivo studies understand its better. Lastly, comparisons made using molecular docking calculations find theoretical activities (M1-5). score parameter 2DO4 protein −5.67, 5JPZ −5.72, finally, 2H80 −5.50. Molecular dynamic are for 0–100 ns. ADME/T performed drug results suggest our candidate exhibits strong co-administration antigen structures, owing low rate interactions decreased over time.Communicated by Ramaswamy H. SarmaKeywords: basesSchiff basesmolecular dockingADME/Tcell culture Disclosure statementNo conflict interest was reported authors.Additional informationFundingThis research funded Sivas Cumhuriyet University Scientific Research Project Fund underneath project number RGD-020 Kafkas 2018-FM-46. This study supported TUBITAK ULAKBIM's High Performance Grid Computing Center (TR-Grid e-Infrastructure).

Язык: Английский

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Small molecule– and peptide–drug conjugates addressing integrins: A story of targeted cancer treatment

Journal of Peptide Science, Год журнала: 2024, Номер 30(7)

Опубликована: Фев. 21, 2024

Targeted cancer treatment should avoid side effects and damage to healthy cells commonly encountered during traditional chemotherapy. By combining small molecule or peptidic ligands as homing devices with cytotoxic drugs connected by a cleavable non‐cleavable linker in peptide–drug conjugates (PDCs) molecule–drug (SMDCs), tumours can be selectively targeted. The development of highly affine, selective peptides molecules recent years has allowed PDCs SMDCs increasingly compete antibody‐drug (ADCs). Integrins represent an excellent target for because they are overexpressed most the broad knowledge about native binding partners well multitude small‐molecule that have been developed over last 30 years. In particular, integrin α V β 3 addressed using variety different two decades, following various strategies. This review summarises describes integrin‐addressing while highlighting points great interest.

Язык: Английский

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Targeting the interplay between MMP-2, CA II and VEGFR-2 via new sulfonamide-tethered isomeric triazole hybrids; Microwave-assisted synthesis, computational studies and evaluation

Bioorganic Chemistry, Год журнала: 2022, Номер 124, С. 105816 - 105816

Опубликована: Апрель 16, 2022

Язык: Английский

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Anticancer Activity of Mannich Bases: A Review of Recent Literature

ChemMedChem, Год журнала: 2022, Номер 17(16)

Опубликована: Июнь 9, 2022

This report summarizes the latest published data on antiproliferative action and cytotoxic activity of Mannich bases, a structurally heterogeneous category chemical entities that includes compounds which are synthesized via grafting an aminomethyl function onto diverse substrates by means reaction. The present overview topic is update to information assembled in previously review covered literature up 2014.

Язык: Английский

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Novel Mannich bases derived from 1,2,4-triazoles: Design, synthesis, characterization, and glutathione S-transferase inhibition properties investigations

Journal of Molecular Structure, Год журнала: 2023, Номер 1293, С. 136321 - 136321

Опубликована: Июль 30, 2023

Язык: Английский

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The Current Landscape of 1,2,3‐triazole Hybrids With Anticancer Therapeutic Potential: Part II

Archiv der Pharmazie, Год журнала: 2025, Номер 358(4)

Опубликована: Апрель 1, 2025

Chemotherapy has been identified as a validated and critically important strategy for the treatment of cancer, but multidrug resistance serious side effects remain grand challenges effective cancer therapy. This highlights urgent need development alternative chemical entities that can modulate more than one biological target with high specificity multitargeted mechanism action in disease progression pathway. 1,2,3-Triazole hybrids have potential to act on dual/multiple targets cells simultaneously possess potent broad-spectrum activity against various cancers, including drug-resistant forms. Thus, 1,2,3-triazole are valuable scaffolds eradication cancer. review provides comprehensive overview evolving landscape their vitro vivo anticancer potential, structure-activity relationships well mechanisms also discussed, covering articles published from 2021 onward.

Язык: Английский

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Sanguinarine targets the catalytic domain of MMP-9: Molecular dynamics and in vitro studies in MDA-MB 468 breast cancer cells

Gene Reports, Год журнала: 2025, Номер unknown, С. 102215 - 102215

Опубликована: Апрель 1, 2025

Язык: Английский

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Novel Benzimidazole‐1,2,3‐Triazole Hybrids: Synthesis, Dual Antimicrobial, Anticancer Activity, Mechanistic Insights, and Computational Studies

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

Опубликована: Апрель 1, 2025

Abstract This study reports the synthesis and biological evaluation of two series novel hybrid heterocyclic scaffolds tethering 1,2,3‐triazole benzimidazole moieties using click chemistry approach. Aromatic azides were synthesized from aniline derivatives followed by preparation S‐propargylated intermediates. These intermediates then reacted with through 1,3‐dipolar cycloaddition to yield benzimidazole‐1,2,3‐triazole hybrids. The compounds fully characterized NMR spectroscopy. Biological testing revealed significant antibacterial, antifungal, cytotoxic activities. Notably, acetamide‐linked 1,2,3‐triazole‐benzimidazole hybrids exhibited potent activity against Gram‐negative bacteria fungal strains MIC values 0.156–0.312 mg/mL several demonstrating selectivity cancer cell lines, particularly HepG‐2 A‐549 IC 50 7–30 µg/mL. EGFR‐TK enzyme inhibition assays further highlighted potential these as anticancer agents. Docking simulation was done for most active 5d 9f promising triazole hits different linker structures interaction analogs both valuable targets contributing growth such as; EGFRWT EGFRT790 in disease; fragments contributions are able stabilize molecular interactions. bioactivity positions them candidates optimization development broad‐spectrum antimicrobial

Язык: Английский

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