Through the present work the 3-oxo-N,3-diphenylpropamide derivatives 5a,b were used to synthesize pridine, pyrazole and thiophene derivatives. 3-Phenylisoxazol-5(4H)-one produced from the reaction of ...ethyl benzoylacetate was used as the key starting compound for different multi-component reactions. The synthesized compounds were evaluated toward Hepatocellular carcinoma HepG2 and cervical carcinoma HeLa cell lines. Compounds 3b, 5b, 7b, 7d, 9c, 9d, 15e, 15f, 16b, 18b, 18e, 18f, 19e and 19f were the most cytotoxic compounds against the tested cell lines. The results obtained in this work encourage further work in the future to produce new cytotoxic compounds.
KEY WORDS: Diphenylpropamide, 3-Phenylisoxazole, Pyran, Pyridine, Cytotoxicity
Bull. Chem. Soc. Ethiop. 2023, 37(1), 141-158.
DOI:https://dx.doi.org/10.4314/bcse.v37i1.12
The N‐(arly)propanamide derivatives 3a,b were used for a series of heterocyclization reactions to give thiophene, pyran, and pyridine derivatives. Thus, these compounds underwent the Gewald's ...thiophene synthesis through their reactions with either malononitrile or ethyl cyanoacetate and elemental sulfur to afford compounds 6a‐f, respectively. In addition, they were subjected through a series of multicomponent reactions (MCRs) to give pyran and fused derivatives. The reactions of 3a,b with either malononitrile or ethyl cyanoacetate gave pyridine derivatives 14a‐d, respectively. The latter compounds afforded arylhydrazone derivatives 15a‐m through their reactions with any of the aromatic diazonium salts 15a‐c. The antitumor of the synthesized compounds against A549 (nonsmall cell lung cancer), H460 (human lung cancer), HT‐29 (human colon cancer), and MKN‐45 (human gastric cancer cancer) cancer cell lines together with foretinib as the positive control by a MTT assay was measured, and the results obtained showed that many compounds exhibited high potency against the six cancer cell lines.
Benzoylacetone (1) underwent a series of multi-component reactions with aromatic aldehydes and malononitrile or ethyl cyanoacetate to produce the pyran derivatives 4a-f. The latter compounds reacted ...with malononitrile or ethyl cyanoacetate to yield the condensation products 5a-m. On the other hand, the reaction of 4a-f with either the diazonium salts 6a-c yielded the arylhydrazone derivatives 7a-i. The multi-component reaction of (1) with aromatic adehydes and cyclohexan-1,3-dione produced the pyran derivatives 9a-c. Compound 1 underwent the Gewald’s reactions with elemental sulfur and malononitrile or ethyl cyanacetate yielding the thiophene derivatives 10a,b. Evaluations of the synthesized products were carried out against some selected cancer cell lines and the most active compounds were further evaluated against the seventeen cancer cell lines classified according to the disease. Morphological changes of A549 cell line by the effect of compound 7k was studied using microenvironment of the lung tissue where an excellent results was obtained.
KEY WORDS: Benzoylacetone, Multi-component reactions, Pyran, Thiophene, Arylhydrazone, Cytotoxicity
Bull. Chem. Soc. Ethiop. 2023, 37(2), 405-425.
DOI: https://dx.doi.org/10.4314/bcse.v37i2.12
This case concerns an 18-month-old with masked congestive heart failure (CHF) from an unrepaired vein of Galen malformation and superior sinus venosus defect who progressed to severe, refractory CHF ...following superior sinus venosus defect repair. Partial transvenous coil embolization of a very-high-risk vein of Galen malformation resolved CHF symptoms. (Level of Difficulty: Advanced.)
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Regulated protein degradation in eukaryotes is performed by the 26S proteasome, which contains a 19-subunit regulatory particle (RP) that binds, processes, and translocates substrates to a 28-subunit ...hollow core particle (CP) where proteolysis occurs. In addition to its intrinsic subunits, myriad proteins interact with the proteasome transiently, including factors that assist and/or regulate its degradative activities. Efforts to identify proteasome-interacting components and/or to solve its structure have relied on over-expression of a tagged plasmid, establishing stable cell lines, or laborious purification protocols to isolate native proteasomes from cells. Here, we describe an engineered human cell line, derived from colon cancer HCT116 cells, with a biotin handle on the RP subunit hRpn1/PSMD2 (proteasome 26S subunit, non-ATPase 2) for purification of 26S proteasomes. A 75-residue sequence from Propionibacterium shermanii that is biotinylated in mammalian cells was added following a tobacco etch virus protease cut site at the C terminus of hRpn1. We tested and found that 26S proteasomes can be isolated from this modified HCT116 cell line by using a simple purification protocol. More specifically, biotinylated proteasomes were purified from the cell lysates by using neutravidin agarose resin and released from the resin following incubation with tobacco etch virus protease. The purified proteasomes had equivalent activity in degrading a model ubiquitinated substrate, namely ubiquitinated p53, compared to commercially available bovine proteasomes that were purified by fractionation. In conclusion, advantages of this approach to obtain 26S proteasomes over others is the simple purification protocol and that all cellular proteins, including the tagged hRpn1 subunit, remain at endogenous stoichiometry.
Ferritin is an acute-phase reactant that is elevated in several autoimmune disorders. Serum ferritin levels have been correlated with disease activity scores of juvenile systemic lupus erythematosus ...(JSLE). Furthermore, enhanced levels of ferritin have also been described in lupus nephritis (LN).
To evaluate serum ferritin as a cheap and available marker of disease activity and renal involvement in Egyptian children with JSLE.
Forty-eight JSLE cases recruited from the Pediatric Rheumatology Clinic in Cairo University Specialized Children’s Hospital and 43 matched healthy children were enrolled in the study. SLE disease activity score-2000 (SLEDAI-2K) and renal activity score were assessed. Serum levels of ferritin, was quantified by enzyme-linked immunosorbent assay.
The mean age of the patients was 12.6 ± 3.02 years and disease duration 3.4 ± 2.5 years. Serum ferritin significantly higher in patients (416.1 ± 1022.9 ng/ml) compared with control (36.1 ± 18.2 ng/ml) (p < 0.001). Serum ferritin was significantly higher in active (n = 20) (890.4 ± 1474.8 ng/ml) compared to inactive (n = 28) (77.4 ± 74.1 ng/ml) patients (p < 0.001). A significant correlation was found between serum ferritin with SLEDAI-2K (r = 0.35, p = 0.014), renal-SLEDAI-2K (r = 0.49, p < 0.001) and with renal activity score (r = 0.38, p = 0.008). A significant correlation was found between serum ferritin and anti-double stranded-DNA (r = 0.44, p = 0.002) and complement 3 (r = −0.42, p = 0.003).
Serum ferritin level can be considered a reliable biomarker for monitoring disease and renal activity in children with JSLE and LN. This may lead to improvement of management and consequently prognosis of JSLE patients as serum ferritin is an available and relatively cheap marker.
The efficacy of chemotherapy continues to be limited due to associated toxicity and chemoresistance. Thus, synthesizing and investigating novel agents for cancer treatment that could potentially ...eliminate such limitations is imperative.
The current study aims to explore the anticancer potency of cryptolepine (CPE) analog on Ehrlich ascites carcinoma cells (EACs) in mice.
The effect of a CPE analog on EAC cell viability and ascites volume, as well as malonaldehyde, total antioxidant capacity, and catalase, were estimated. The concentration of caspase-8 and mTOR in EACs was also measured, and the expression levels of PTEN and Akt were determined.
Results revealed that CPE analog exerts a cytotoxic effect on EAC cell viability and reduces the ascites volume. Moreover, this analog induces oxidative stress in EACs by increasing the level of malonaldehyde and decreasing the level of total antioxidant capacity and catalase activity. It also induces apoptosis by elevating the concentration of caspase-8 in EACs. Furthermore, it decreases the concentration of mTOR in EACs. Moreover, it upregulates the expression of PTEN and downregulates the expression of Akt in EACs.
Our findings showed the anticancer activity of CPE analog against EACs in mice mediated by regulation of the PTEN/Akt/mTOR signaling pathway.
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