Novel peptide inhibitors targeting CD40 and CD40L interaction: A potential for atherosclerosis therapy DOI Creative Commons

Kundan Solanki,

Ashutosh Kumar, M. S. Khan

и другие.

Current Research in Structural Biology, Год журнала: 2023, Номер 6, С. 100110 - 100110

Опубликована: Янв. 1, 2023

Atherosclerosis is a chronic inflammatory disease characterized by plaque build-up in the arteries, leading to obstruction of blood flow. Macrophages are primary immune cells found atherosclerotic lesions and directly involved atherosclerosis progression. derived from extravasating monocytes. The monocytic CD40 receptor important for monocyte recruitment on endothelium expressing ligand (CD40L). Thus, targeting monocyte/macrophage interaction with inhibiting CD40−CD40L may be promising strategy attenuating atherosclerosis. Monoclonal antibodies have been used against this target but shows various complications. We an array computer-aided drug discovery tools molecular docking approaches design therapeutic inhibitory peptide that could efficiently bind critical residues (82Y, 84D, 86N) receptor; essential receptor's binding CD40L. initial screen identified parent high affinity CD40, exhibited positive hepatotoxicity score. then designed several novel peptidomimetic derivatives higher affinities good physicochemical properties, negative as compared peptide. Furthermore, we conducted dynamics simulations both apo complexed forms ligand, screened peptides evaluate their stability. therapeutics potentially attenuate

Язык: Английский

Synthesis, biofilm formation inhibitory, and inflammation inhibitory activities of new coumarin derivatives DOI Creative Commons

Ghada E. Ahmed,

Zeinab A. Elshahid, Eslam R. El‐Sawy

и другие.

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Апрель 20, 2024

Abstract Coumarins are heterocycles of great interest in the development valuable active structures chemistry and biological domains. The ability coumarins to inhibit biofilm formation Gram positive bacterium ( Staphylococcus aureus ), negative Escherichia coli ) as well methicillin-resistant S. (MRSA) has been previously described. In present work, new hybrid coumarin-heterocycles have synthesized via reaction coumarin-6-sulfonyl chloride 6-aminocoumarin with different small heterocycle moieties. efficacy compounds was evaluated towards their anti-inflammatory properties. antimicrobial activities newly were tested against ATCC 6538), E. 25922), yeast Candida albicans 10231) fungus Aspergillus niger NRRL-A326). Compounds 4d , 4e 4f 6a 9 showed significant MIC MBC values C. especial incidence on compound which surpasses all other giving (4.88 9.76 µg/mL for (78.13 312.5 (9.77 78.13 (39.06 76.7 MRSA), respectively. With reference antibiofilm activity, exhibited potent activity IC 50 60, 133.32, 19.67 aureus, coli, MRSA, (respectively) considering drug (neomycin). Out studied compounds, results indicated that effectively inhibited nitric oxide production lipopolysaccharide-(LPS-) stimulated RAW264.7 macrophage cells, NO% inhibition 70% compared Sulindac (55.2%)

Язык: Английский

Процитировано

9
Advances in synthesis, medicinal properties and biomedical applications of Pyridine Derivatives: A Comprehensive Review DOI Creative Commons
Duryodhan Sahu, P.S. Rama Sreekanth, Prasanta Kumar Behera

и другие.

European Journal of Medicinal Chemistry Reports, Год журнала: 2024, Номер 12, С. 100210 - 100210

Опубликована: Сен. 6, 2024

Язык: Английский

Процитировано

9
Innovative colorimetric detection of clinical Gram-negative bacteria using low-cost bacteriostatic barbiturate polymers DOI Creative Commons
Joana Galhano, Atanas Kurutos, Georgi M. Dobrikov

и другие.

Materials Today Chemistry, Год журнала: 2024, Номер 36, С. 101951 - 101951

Опубликована: Фев. 6, 2024

This study introduces the synergistic antibacterial activity derived from combination of barbituric acid derivatives with PVC, PMMA and PMMMA polymers. The barbiturates - C1, C2, C3, exhibit potent Minimum Inhibitory Concentration (MIC) values clear selectivity towards Gram-positive bacteria in solution, resulting inhibitory at exceptionally low concentrations (0.19–0.0015 μg/mL). By integrating these within polymeric matrices, an advanced polymer was obtained. novel material facilitates dual benefit detecting Gram-negative bacterial colonies via colorimetric alterations, while simultaneously providing a broad-spectrum approach, effective against both bacteria. potential barbiturate-enhanced polymers is substantial, not least because their cost-effective nature. Their inherent feature enabling naked-eye selective positions them as efficient, onsite tool for monitoring contamination by E. coli P. aeruginosa clinical environments. Thus, open new horizon innovative, rapid, low-cost strategies microbial control patient safety.

Язык: Английский

Процитировано

4
Microwave-assisted synthesis and in vitro and in silico studies of pyrano[3,2-c]quinoline-3-carboxylates as dual acting anti-cancer and anti-microbial agents and potential topoisomerase II and DNA-gyrase inhibitors DOI Creative Commons
Ashraf A. Aly,

Hisham A. Abd El-Naby,

Essam Kh. Ahmed

и другие.

RSC Advances, Год журнала: 2025, Номер 15(3), С. 1941 - 1956

Опубликована: Янв. 1, 2025

A microwave-assisted method was utilized to synthesize novel pyranoquinolone derivatives as dual acting topoisomerase II/DNA gyrase inhibitors with apoptosis induction ability for halting lung cancer and staphylococcal infection.

Язык: Английский

Процитировано

0
Synthesis and in vitro anti-bacterial activity of novel quinoline-based aryl/heteroaryl amide hybrids DOI

Mahya Ghods,

Ali Almasirad, Azar Tahghighi

и другие.

Journal of Molecular Structure, Год журнала: 2025, Номер unknown, С. 141923 - 141923

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Design, synthesis, and antiproliferative screening of new quinoline derivatives bearing a cis-vinyl triamide motif as apoptosis activators and EGFR-TK inhibitors DOI Creative Commons
Hany M. Abd El‐Lateef,

Ahmed Gaafar Ahmed Gaafar,

Arwa Sultan Alqahtani

и другие.

RSC Advances, Год журнала: 2024, Номер 14(34), С. 24781 - 24790

Опубликована: Янв. 1, 2024

A set of novel quinoline tethered cis -vinyl triamides derivatives has been designed, synthesized and screened for in vitro cytotoxicity against the MCF-7 breast adenocarcinoma cell line.

Язык: Английский

Процитировано

3
Design, synthesis and antiproliferative screening of newly synthesized coumarin-acrylamide hybrids as potential cytotoxic and apoptosis inducing agents DOI Creative Commons
Hany M. Abd El‐Lateef,

Lina M. A. Abdel Ghany,

Rasha Mohammed Saleem

и другие.

RSC Advances, Год журнала: 2023, Номер 13(46), С. 32547 - 32557

Опубликована: Янв. 1, 2023

A sequence of novel coumarin-acrylamide hybrids has been synthesized and evaluated for their in vitro cytotoxicity against HepG2 liver cancer cells.

Язык: Английский

Процитировано

8
Introducing of novel class of pyrano[2,3-c]pyrazole-5-carbonitrile analogs with potent antimicrobial activity, DNA gyrase inhibition, and prominent pharmacokinetic and CNS toxicity profiles supported by molecular dynamic simulation DOI
Mohammed Almaghrabi, Arafa Musa, Ahmed K. B. Aljohani

и другие.

Journal of Biomolecular Structure and Dynamics, Год журнала: 2023, Номер 42(18), С. 9529 - 9546

Опубликована: Сен. 3, 2023

AbstractMicrobiological DNA gyrase is recognized as an exceptional microbial target for the innovative development of low-resistant and more effective antimicrobial drugs. Hence, we introduced a one-pot facile synthesis novel pyranopyrazole scaffold bearing different functionalities; substituted aryl ring, nitrile, hydroxyl groups. All new analogs were characterized with full spectroscopic data. The screening all was assessed against standard strains Gm + ve Gm-ve through in vitro considers. screened compounds displayed very promising MIC/MBC values some bacterial broad or selective antibacterial effects. Of these, 4j biphenyl analog showed 0.5-2/2-8 µg/mL suppression killing strains. Moreover, most potent certain highly resistant Consequently, supercoiling assay done using ciprofloxacin reference positive control. Obviously, results activity profile IC50 value 6.29 better than drug 10.2 µg/mL. Additionally, CNS toxicity testing HiB5 cell line attenuation GABA/NMDA expression to both that revealed neurotransmitter modulation by scaffold. Importantly, docking dynamic simulations performed active investigate its interaction binding sites, which supported observations compound stability pocket. Finally, inhibitor prominent efficacy low side effect quinolones.Communicated Ramaswamy H. SarmaKeywords: PyranopyrazoleDNA gyraseantimicrobial activitydockingmolecular dynamicsNMDA receptorsciprofloxacin Disclosure statementNo potential conflict interest reported authors.AcknowledgmentsThe authors extend their appreciation Deanship Scientific Research at Jouf University under Grant Number (DSR-2021-01-03104).Additional informationFundingThis work funded grant No (DSR-2021-01-03104).

Язык: Английский

Процитировано

7
Synthesis, characterization and biological research of novel 2-(quinoline-4-carbonyl)hydrazide-acrylamide hybrids as potential anticancer agents on MCF-7 breast carcinoma cells by targeting EGFR-TK DOI Creative Commons
Hany M. Abd El‐Lateef, Duaa Bafail,

Noura Hamdi Yousef Alhalees

и другие.

RSC Advances, Год журнала: 2024, Номер 14(32), С. 23495 - 23504

Опубликована: Янв. 1, 2024

A sequence of novel 2-(quinoline-4-carbonyl)hydrazide scaffolds carrying the acrylamide moiety have been synthesized and evaluated for in vitro cytotoxicity against an MCF-7 breast cancer cell line.

Язык: Английский

Процитировано

2
Novel Acrylate-Based Derivatives: Design, Synthesis, Antiproliferative Screening, and Docking Study as Potential Combretastatin Analogues DOI Creative Commons
Eman Fayad,

Sarah Awwadh Altalhi,

Matokah M. Abualnaja

и другие.

ACS Omega, Год журнала: 2023, Номер 8(41), С. 38394 - 38405

Опубликована: Окт. 9, 2023

A variety of 3-(4-chlorophenyl) acrylic acids 4a,b and 3-(4-chlorophenyl)acrylate esters 5a-i were synthesized structurally proven by spectroscopic studies such as IR, 1H NMR, 13C NMR well mass spectrometry. All substances investigated for their antiproliferative efficacy against the MDA-MB-231 cell line. Among these, acid compound 4b demonstrated most potent cytotoxic effect with an IC50 value 3.24 ± 0.13 μM, compared to CA-4 (IC50 = 1.27 09 μM). Additionally, molecule displayed inhibitory β-tubulin polymerization a percentage inhibition 80.07%. Furthermore, was found produce considerable cycle arrest at G2/M stage cellular death, FACS analysis. In addition, in vivo antitumor screening sodium salt carried out, results have shown that tested showed significant decrease viable EAC count volume, accompanied increase life span prolongation, if positive control group. molecular modeling performed understand how highly efficient chemicals 5e interact colchicine-binding region on tubulin. This work aims shed light reasons behind exceptional cytotoxicity better capacity inhibit tubulin comparison CA-4.

Язык: Английский

Процитировано

4