In-vitro cytotoxic and radiosensitizing evaluation of novel 2-pyridone, isoquinoline, chromene and chromenopyridone derivatives

On the account of the reported anticancer activity of 2-pyridone, a new series of ethyl-1,6-dihydropyridine-3-carboxylate (4a-j), 1-oxo-1,2-dihydroisoquinoline-7-carbonitrile (6a-h), 2H-chromene (7,8) and 3H-chromeno[3,4-c]pyridone derivatives (9,10) were synthesized and tested for in-vitro anticancer activity against Ehrlich Ascites Carcinoma (EAC) cell line and human liver cell line (HEPG2). The structures of the synthesized compounds were confirmed by analytical and spectral data. Furthermore, radiosensitization study was performed for the most potent compounds (4a, 4d, 6a, 6c, 6e and 10)

Sinteza, in vitro antitumorsko ispitivanje i radiosenzitirajuće vrednovanje novih derivata 4-[3-(supstituiranih)tioureido]-N-(kinoksalin-2-il)benzensulfonamida

Sulfonamides and quinoxaline derivatives possess many types of biological activities and have been recently reported to show substantial antitumor activity. This paper reports the synthesis of novel thioureidosulfaquinoxaline derivatives. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against a human liver cell line (HEPG2) and showed higher activity than the reference drug doxorubicin. 4-(3-(4-Ethylbenzoate)thioureido)-N-(quinoxalin-2-yl)benzenesulfonamide (9) (IC50 = 15.6 µmol L1), N-(pyridin-2-yl)-4-(3-(4-(N-quinoxalin-2-yl-sulfamoyl)phenyl)thioureido)benzene-sulfonamide (10) (IC50 = 26.8 µmol L1) and N-(quinoxalin-2-yl)-4-(3-(4-(N-thiazol-2-ylsulfamoyl)phenyl)thioureido)benzenesulfonamide (11) (IC50 = 24.4 µmol L1) were the most potent compared to doxorubicin (IC50 = 71.8 µmol L1). The most potent compounds 9, 10 and 11 were evaluated as radiosensitizing agents by subjecting the compounds to γ-irradiation (8 kGy).Derivati sulfonamida i kinoksalina imaju raznoliko biološko djelovanje, između ostalog i antitumorsko djelovanje. U radu je opisana sinteza novih derivata tioureido sulfakinoksalina. Svim novim spojevima ispitano je antitumorsko djelovanje in vitro na humanoj staničnoj liniji jetre (HEPG 2). Svi ispitani spojevi pokazuju jači učinak nego referentni lijek doksorubicin. Najjači učinak imali su 4-(3-(4-etilbenzoat)tioureido)-N-(kinoksalin-2-il)benzen-sulfonamid (9) (IC50 = 15,6 µmol L1), N-(piridin-2-il)-4-(3-(4-(N-kinoksalin-2-il-sulfamoil)fenil)tioureido)-benzen-sulfonamid (10) (IC50 = 26,8 µmol L1) i N-(kinoksalin-2-il)-4-(3-(4-(N-tiazol-2-ilsulfamoil)fenil)tioureido)benzen-sulfonamid (11) (IC50 = 24,4 µmol L1), dok je IC50 vrijednost bila 71,8 µmol L1. Najaktivniji spojevi 9, 10 i 11 evaluirani su kao radziosenzitirajuća sredstva nakon izlaganja spojeva γ-zračenju (8 kGy)

Synthesis, Characterization and Anti-Breast Cancer Activity of New 4-Aminoantipyrine-Based Heterocycles

4-Aminoantipyrine was utilized as key intermediate for the synthesis of pyrazolone derivatives bearing biologically active moieties. The newly synthesized compounds were characterized by IR, 1H- and 13C-NMR spectral and microanalytical studies. The compounds were screened as anticancer agents against a human tumor breast cancer cell line MCF7, and the results showed that (Z)-4-((3-amino-5-imino-1-phenyl-1H-pyrazol-4(5H)-ylidene)methylamino)-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one 5, 3-(4-bromophenyl) -1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 13, 1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-3-(4-iodophenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 14, 3,3′-(4,4′-sulfonylbis(4,1-phenylene))bis(1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile) 16, (Z)-1- (1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2-hydrazono-4-oxo-3-phenyl-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 17, (Z)-1-(1,5-dimethyl-3-oxo-2-phenyl- 2,3-dihydro-1H-pyrazol-4-yl)-4-oxo-3-phenyl-2-(2-phenylhydrazono)-1,2,3,4-tetrahydro pyrimidine-5-carbonitrile 18, and (Z)-4-(3-amino-6-hydrazono-7-phenyl-6,7-dihydro pyrazolo[3,4-d]pyrimidin-5-yl)-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one 19 were the most active compounds with IC50 values ranging from 30.68 to 60.72 µM compared with Doxorubicin as positive control with the IC50 value 71.8 µM

Synthesis and Anti-Breast Cancer Evaluation of Novel N-(Guanidinyl)benzenesulfonamides

A series of 4-(substituted)-N-(guanidinyl)benzenesulfonamides bearing biologically active pyrazole, pyrimidine and pyridine moieties were prepared and evaluated for their anticancer activity against human tumor breast cell line (MCF7). These sulfonamides showed promising activity with IC50 values ranging from 49.5 to 70.2 μM. The structure-activity relationship of the synthesized compounds was studied. Interestingly, it was found that the most potent compounds in this study were the corresponding 2-cyanoacrylate 3, 3-oxobutanoate 4, pyrazole 6, pyridine 9 and pyrazole 13. Compounds 7 and 8 are nearly as active as Doxorubicin as reference drug with (IC50 values = 70.2, 68.1 μM), while compounds 5, 10 and 11 exhibited a moderate activity

In-Vitro Anticancer Evaluation of Some Novel Thioureido-Benzensulfonamide Derivatives

A novel series of sulfonamide derivatives (14 compounds) bearing thiourea moieties were efficiently synthesized and evaluated for their possible in vitro anticancer activity against four human tumor cell lines. The results indicated that compound 6 was the most potent, showing effectiveness on all the tested cell lines. Compounds 7 and 10 also showed promising results

Study of interleukin 33 in rheumatoid arthritis versus osteoarthritis patients

Aim of the work To compare the expression of serum interleukin 33 (IL33), a new member of the interleukin1 (IL-1) cytokine family, in rheumatoid arthritis (RA) versus osteoarthritis (OA) patients and to correlate it with clinical, laboratory and radiographic parameters. Subjects and methods 20 RA and 20 primary knee OA patients. The levels of serum IL-33 were measured by enzyme-linked immunosorbent assay (ELISA) while anticyclic citrullinated peptide (Anti-CCP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured by standard laboratory techniques. Plain x-ray of both hands and wrists were evaluated using the modified Larsen score 1995 (MLS) in RA patients. Knee OA grading was performed according to the KellgrenLawrence classification. The correlation of IL-33 level with clinical, laboratory and radiological data of RA and OA was analyzed. Results Serum IL-33 level was significantly higher in RA than in OA patients (P < 0.001). This level was positively correlated with disease duration, clinical and laboratory markers of disease activity, impaired functional status and radiographic severity in RA while not in OA patients. Conclusions These findings support that IL-33 could have an essential proinflammatory role in the pathogenesis of RA and that IL-33 level may be a monitor of disease activity and severity. IL-33 may become therapeutic target for RA

Study of the level of stem cell factor in patients with bronchial asthma

Aim of the work: The aim of this study was to assess serum level of stem cell factor in asthmatic patients and its relation to disease severity. Methods: This case control study was carried out on 70 individuals classified into 20 healthy control subjects and 50 asthmatic patients that were admitted in Chest Department, Benha university hospital in the period between March 2013 and December 2014. Asthma diagnosis (history and PFT) and assessment of its severity were conducted according to the guidelines of Global Initiative for Asthma (GINA, 2011). Eosinophil percentage in the sputum of asthmatic patients was done. Measurement of stem cell factor (SCF) in the sera was done by Enzyme-Linked Immunosorbent Assay. Results: Our results found a statistically significant difference (P value < 0.001) between asthmatic patients and control subjects in the mean values of SCF (1192.34 ± 789.89 versus 326.29 ± 274.38 respectively). There was a statistically significant difference (P value = 0.001) between eosinophilic and non eosinophilic phenotype (1457.77 ± 648.83 versus 130.59 ± 83.27 respectively). There was a statistically significant difference in the level of SCF among different degrees of asthma severity (P = 0.001). Also, there was a significant negative correlation (r = −0.288) between SCF levels and FEV1% and significant positive correlation between SCF levels and sputum (r = 0.712) and blood (r = 0.548) eosinophils% in asthmatic patients. Conclusion: This study demonstrated that the serum level of SCF was higher in asthmatic patients especially among eosinophilic phenotype than among healthy control subjects. Also there was a significant association between higher SCF and higher levels of asthma severity, sputum and blood eosinophil%