Design, synthesis and SAR of novel sulfonylurea derivatives for the treatment of Diabetes mellitus in rats

Sroor, Farid M.; Basyouni, Wahid M.; Aly, Hanan F.; Ali, Sanaa A.; Arafa, Amany A.

doi:10.1007/s00044-021-02829-z

Cited by 14 publications

(2 citation statements)

References 42 publications

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“…Based on these facts and in continuation to our research interest in the synthesis of bioactive compounds [3,4,18,26–35] we report herein the synthesis of novel series of cyanoacrylamides linked to tetrahydrobenzo[ b ]thiophene moiety and test their cytotoxic activities against various cancer cell lines using MTT assay.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic Effect of New (E)‐2‐Cyano‐N‐(tetrahydrobenzo[b]thiophen‐2‐yl)acrylamide Derivatives: Down‐Regulation of RBL2 and STAT2 and Triggering of DNA Damage in Breast Carcinoma

Ibrahim,

Sroor,

Mahrous

et al. 2023

ChemistrySelect

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A novel series of 2‐cyano‐N‐(tetrahydrobenzo[b]thiophen‐2‐yl)acrylamide derivatives were synthesized and their structures were confirmed using several spectral tools. All compounds were subjected to MTT assay to elucidate their cytotoxic effect against human hepatocellular carcinoma (HEPG2), human Caucasian breast adenocarcinoma (MCF7), human pancreatic cancer cell line (PACA2), human prostate cancer cell line (PC3), and normal skin fibroblast (BJ1). Among them, the acrylamide derivatives 5, 10 and 14 exerted potent activities against MCF7 with IC50 values of 61.2, 66.4, and 55.3 μg/ml respectively. A molecular docking was performed to study the possibility of the molecular binding of these three compounds with the active site of signal transducer and activator of transcription 1 protein (STAT1). Gene expression analysis demonstrated the significant down‐regulation of RBL2 (RB transcriptional corepressor like 2) and STAT2 (Signal transducer and activator of transcription 2) in treated MCF7 cells and also showed the significant effect in down‐regulating KRAS (Ki‐ras2 Kirsten rat sarcoma viral oncogene homolog) and SMAD (Sma and Mad proteins) genes in PC3 cells. Comet assay revealed the best effect of Ethyl 2‐(2‐cyano‐3‐(3,4‐dimethoxyphenyl)acrylamido)‐4,5,6,7‐tetrahydrobenzo[b]thiophene‐3‐carboxylate in damaging the DNA of MCF7 cells (18.75±1.50 %). Also, DNA fragmentation was studied electrophoretically, which confirmed the results of the comet assay.

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Section: Introductionmentioning

confidence: 99%

Cytotoxic Effect of New (E)‐2‐Cyano‐N‐(tetrahydrobenzo[b]thiophen‐2‐yl)acrylamide Derivatives: Down‐Regulation of RBL2 and STAT2 and Triggering of DNA Damage in Breast Carcinoma

Ibrahim,

Sroor,

Mahrous

et al. 2023

ChemistrySelect

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“…Urea and its derivatives play an essential role in numerous biologically active drugs. Urea derivatives have demonstrated anticancer, [59][60][61][62] hypoglycemic, [63,64] antifungal, [60,65,66] antibacterial, [60,67] antiviral, [49,68] and anticonvulsant [69,70] properties. In this instance, the combination of urea core and tricyclic aromatic hydrocarbons (9-fluorene or phenothiazine), as depicted in Figure 1, was carried out in the hopes that these two prospective moieties would improve the biological properties of the final hybrid compounds as antimicrobial agents.…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, structure elucidation, antimicrobial, molecular docking, and SAR studies of novel urea derivatives bearing tricyclic aromatic hydrocarbon rings

Sroor,

El‐Sayed,

Abdelraof

2024

Archiv der Pharmazie

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The targeted compounds were prepared using both (9H‐fluoren‐9‐ylidene)hydrazine (1) and 10H‐phenothiazine (2) as starting materials. The treatment of 1 or 2 with different isocyanates afforded the title compounds 7a–d, 8a, and 8b in excellent yield. All compounds were characterized and ascertained by infrared, nuclear magnetic resonance, and elemental analyses as well as single‐crystal X‐ray diffraction. The antimicrobial efficiency of all was tested in vitro, and a noticeable inhibition activity against Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans was obtained by compounds 7a, 7b, 8a, and 8b. Moreover, the biofilm mechanism activity was strongly inhibited by compounds 7b and 8b for all bacterial pathogens, with a percentage ratio of more than 55%. The findings from the molecular docking simulation revealed that compounds 7a, 7b, 8a, and 8b exhibited favorable binding energies and interacted effectively with the active sites of sterol 14‐demethylase, dihydropteroate synthase, gyrase B, LasR (major transcriptional activator of P. aeruginosa), and carbapenemase for C. albicans, S. aureus, B. subtills, K. pneumoniae, and P. aeruginosa, respectively. These results suggest that the compounds have the potential to inhibit the activity of these enzymes and demonstrate promising antimicrobial properties. Moreover, the in silico evaluation of drug likeness and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles for compounds 7a, 7b, 8a, and 8b demonstrated their compatibility with Lipinski's, Ghose's, Veber's, Muegge's, and Egan's rules. These findings suggest that these compounds possess favorable physicochemical properties, making them promising candidates for continued drug development efforts.

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Anticancer and antimicrobial activities of new thiazolyl-urea derivatives: gene expression, DNA damage, DNA fragmentation and SAR studies

et al. 2022

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Design, synthesis and SAR of novel sulfonylurea derivatives for the treatment of Diabetes mellitus in rats

Cited by 14 publications

References 42 publications

Cytotoxic Effect of New (E)‐2‐Cyano‐N‐(tetrahydrobenzo[b]thiophen‐2‐yl)acrylamide Derivatives: Down‐Regulation of RBL2 and STAT2 and Triggering of DNA Damage in Breast Carcinoma

Cytotoxic Effect of New (E)‐2‐Cyano‐N‐(tetrahydrobenzo[b]thiophen‐2‐yl)acrylamide Derivatives: Down‐Regulation of RBL2 and STAT2 and Triggering of DNA Damage in Breast Carcinoma

Design, synthesis, structure elucidation, antimicrobial, molecular docking, and SAR studies of novel urea derivatives bearing tricyclic aromatic hydrocarbon rings

Anticancer and antimicrobial activities of new thiazolyl-urea derivatives: gene expression, DNA damage, DNA fragmentation and SAR studies

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