Synthesis and Anticancer Activities of Pyrazole–Thiadiazole-Based EGFR Inhibitors

ACS Omega, Journal Year: 2023, Volume and Issue: 8(34), P. 31500 - 31509

Published: Aug. 17, 2023

Lung cancer is one of the most common types with highest mortality rates. However, while epidermal growth factor receptor (EGFR) an important parameter for lung cancer, EGFR inhibitors also show great promise in treatment disease. Therefore, a series new inhibitor candidates containing thiadiazole and pyrazole rings have been developed. The activities synthesized compounds were elucidated by vitro MTT, (which chemically 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), cytotoxicity assay, analysis mitochondrial membrane potential (MMP) flow cytometry, inhibition experiments. Molecular docking molecular dynamics simulations performed as silico studies. Compounds 6d, 6g, 6j showed activity against A549 cell line IC50 = 5.176 ± 0.164; 1.537 0.097; 8.493 0.667 μM values, respectively. As result MMP compound 6g 80.93% potential. According to results obtained inhibitory shows on enzyme value 0.024 0.002 μM.

Language: Английский

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Development of Orally Active Anti-Inflammatory Agents: In Vivo and In Silico Analysis of Naphthalene-Chalcone Derivatives Based on 2-Acetyl-6-Methoxy Naphthalene

Chemical Physics Impact, Journal Year: 2024, Volume and Issue: 8, P. 100472 - 100472

Published: Jan. 11, 2024

Chalcone compounds are reported to have diverse biological activities such as antiviral, antimicrobial, antimalarial, antitumor, antifungal, anticancer, and so forth. Herewith, we wish report the in-vivo anti-inflammatory of previously synthesized naphthalene-chalcone hybrids from 2-Acetyl-6-Methoxy Naphthalene derivatives (C1-C25). All chalcones (C1-C25) were thoroughly characterized with standard spectroscopic techniques tested for their activities. The currently employed in-silico docking methodology uses 'Molegro Virtual Docker' a tool target proteins COX-1 (PDB ID: 1EQH) COX-2 1PXX). Molecular analysis suggested that compound C-24 exhibited higher score -117.495 kcal/mol than flurbiprofen -115.259 on target. To understand more about pharmacokinetics aspects, predicted theoretical ADME properties using 'QikProp, 2022' found all acceptable pharmacokinetic properties.

Language: Английский

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Polygonum minus: A tropical medicinal herb with vast applications in food, agricultural, and medicinal fields

Food Bioscience, Journal Year: 2024, Volume and Issue: 60, P. 104511 - 104511

Published: June 10, 2024

Language: Английский

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Design, synthesis, and antiproliferative activity evaluation of novel cyclic secondary amine containing dithiocarbamate derivatives as potent EGFR inhibitors

Journal of Molecular Structure, Journal Year: 2025, Volume and Issue: unknown, P. 142036 - 142036

Published: March 1, 2025

Language: Английский

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Fluorescent Poly(ε-Caprolactone)s Micelles for Anticancer Drug Delivery and Bioimaging

Biomacromolecules, Journal Year: 2025, Volume and Issue: unknown

Published: April 30, 2025

Despite significant advancements in polymer-based nanomedicine, the clinical translation of biodegradable micellar drug delivery systems is limited due to premature release, low drug-loading capacity (DLC), and lack inherent therapeutic bioimaging functionalities. To overcome these challenges, we designed a novel poly(ε-caprolactone) (PCL)-based amphiphilic diblock copolymer that possesses anticancer activity, fluorescence imaging capabilities, multistimuli-responsive release. This platform features fluorescent hydrophilic shell comprising two triethylene glycol units hydrophobic core containing naphthalene moieties. unique architecture imparts remarkable properties: confer thermoresponsive behavior for precise release enable intracellular tracking, while pendants enhance DLC (3.7%) through π-π interactions with doxorubicin (DOX). The micelles exhibit critical micelle concentration (7.8 × 10-3 g/L), demonstrate strong stability long storage times, show cytotoxicity against MDA-MB-231 cell line, highlighting their combined efficacy.

Language: Английский

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Identification of a New Pentafluorosulfanyl-Substituted Chalcone with Activity Against Hepatoma and Human Parasites

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(1), P. 50 - 50

Published: Jan. 3, 2025

Background/Objectives: New drugs are required for the treatment of liver cancers and protozoal parasite infections. Analogs known anticancer active antileishmanial 2′,4′,6′-trimethoxychalcone SU086 were prepared investigated. Methods: The chalcones according to Claisen–Schmidt condensation protocol analyzed. They tested activity against two cancer cell lines (HepG2 HuH-7) parasites (Toxoplasma gondii Leishmania major). Unspecific toxicity expression Hsp90 Hsp70 upon analyzed in cells. Results: A new chalcone, 2′,4′,6′-trimethoxy-3-pentafluorosulfanylchalcone (246TMP-3SF5), with a pentafluorosulfanyl (SF5) substituent showed pronounced activities cells T. which superior parent chalcone these models. In contrast, its anthracene analog 2′,4′,6′-trimethoxy-9-anthracenylchalcone (246TMP-Anth) most L. major promastigotes. SF5-substituted behaved like inhibitor 17-AAG upregulated Conclusions: has potential become drug therapy hepatoma toxoplasmosis.

Language: Английский

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Exploring the Therapeutic Potential of Chalcones in Oncology: A Comprehensive Review

Current Bioactive Compounds, Journal Year: 2023, Volume and Issue: 20(6)

Published: Nov. 8, 2023

Abstract: Chalcone is a bioactive flavonoid contained in various plants such as Angelica archangelica, Pueraria lobata, and Glycyrrhiza glabra. It has been studied extensively the field of pharmaceutical sciences due to its significant role therapeutic potential including antibacterial, antiinflammatory, analgesic, cytotoxic, anti-tumour properties. A plenty study indicated numerous chalcone derivatives exhibit enhanced potency reduced toxicity compared natural analogues. In this review, we introduce 1- naphthylacetophenone, 2-benzimidazolyl, 2-furoyloxy, 3-(furan-2-yl)pyrazol-4-yl, 4'-alkoxy, 4- anilinoquinolinyl, 4-aryloxyquinazolines, acridine, benzamide, benzenesulfonamide, bischalcone, cinnamoylthiazoles, D-glucosyl azides, dialkylamino, dihydropyrimidinone, indole, isoquinoline, ligustrazine, morpholinothiazole, naphthalene, quinoline, sulphonamide, thiazoleimidazopyridine, thienyl, thiophene, triazines, triazole-benzimidazole, tri-methoxyphenyl, α- trifluoromethyl hybrids display their promising activity against cancer cell lines, breast cancer, prostate colon lung cervical liver cancer.

Language: Английский

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Naphthyl‐Based Chalcone Derivatives: A Multifaceted Player in Medicinal Chemistry

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(19)

Published: May 17, 2024

Abstract Research has placed a great deal of emphasis on molecule development and discovery with substantial biological profiling in recent years. Despite the significant side effects, medicinal chemists have long strived to synthesize drug molecules highest level therapeutic activity lowest possible toxicity. The naphthyl‐based chalcone derivatives drawn attention due their simple structures wide range pharmacological effects. main focus this review is outline biologically active based naphthyl moiety‐substituted developed over A synopsis screening, including relevant structure‐activity relationships, action mechanisms, applications, provided article. It true that prospective hybrids combining moiety different pharmacophores are needed address resistance improve specificity. Therefore, may be useful design new, highly successful drugs previously reported methodologies.

Language: Английский

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Synthesis of Imidazole‐2,3‐dihydrothiazole Compounds as VEGFR‐2 Inhibitors and Their Support with in Silico Studies

Chemistry & Biodiversity, Journal Year: 2023, Volume and Issue: 20(9)

Published: July 28, 2023

In this study, 12 novel 2-((1-(4-(1H-imidazol-1-yl)phenyl)ethylidene)hydrazineylidene)-3-ethyl-4-(substitutephenyl)-2,3-dihydrothiazole derivatives were obtained. Among these compounds, 2-((1-(4-(1H-imidazol-1-yl)phenyl)ethylidene)hydrazineylidene)-4-([1,1'-biphenyl]-4-yl)-3-ethyl-2,3-dihydrothiazole (4h) was chosen as the most active derivative in series. According to MTT results, compounds 4h and 4k showed activity with IC50 =4.566±0.246 μM =4.537±0.463 μM, respectively. Unlike other derivatives, compound carries a phenyl ring 4th position of ring. This bulky group allowed settle enzyme site. Dynamic studies show that stability does not change over 40 ns. RMSD, RMSF Rg parameters all remained within acceptable limits. The uninterrupted aromatic hydrogen bonding site important amino acids Cys919, Glu885 Asp1046 proves inhibitory potential on VEGFR-2 enzyme. It is thought more will be reached synthesized starting from 4h.

Language: Английский

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Naphthylated LEGO-lipophopsphonoxin antibiotics used as a fluorescent tool for the observation of target membrane perturbations preceding its disruption

Methods and Applications in Fluorescence, Journal Year: 2024, Volume and Issue: 13(1), P. 015001 - 015001

Published: Oct. 23, 2024

Abstract Linker-Evolved-Group-Optimized-Lipophosphonoxins (LEGO-LPPO) are small synthetic modular peptidomimetics with promising antimicrobial activity. The LEGO-LPPO mechanism of antibacterial action has been determined to be the depolarization and disruption bacterial membranes. Their nature is advantageous for fine tuning their biological properties. In order optimize structure even further, it important understand interaction membranes at molecular level. this work, we present synthesis five (designated as 1 _naph2-4-G 5 _naph2-4-G) molecules bearing fluorescent naphtylethyl moieties usage in study behaviour membrane. Our goal was characterize fluorescently labelled under conditions that do not completely disrupt membrane, mostly form membrane-bound monomers. We observed intramolecular interactions hydrophobic modules buffer by detecting dynamic naphthyl excimers disappearance after bind into molecule slightly affects membrane fluidity DOPG above phase transition. fluorophore itself fast almost unrestricted rotation around ethylene linking groups ( r inf = 0.010), which indicates a considerable chaotropic effect given depth proved useful model observing antibiotics phospholipid bilayer enabling us decipher its effects on state dynamics; binding penetration particular occupies.

Language: Английский

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