Search

Thirty-four chiral compounds having benzoxadiazole and sulfonamide moieties on the skeleton have been synthesized. The in vitro cytotoxic activity and apoptotic effects of these compounds have been evaluated using the A549 lung cancer cell line.

A series of new chiral thiosemicarbazones derived from homochiral amines in both enantiomeric forms were synthesized and evaluated for their in vitro antiproliferative activity against A549 (human alveolar adenocarcinoma), MCF-7 (human breast adenocarcinoma), HeLa (human cervical adenocarcinoma), and HGC-27 (human stomach carcinoma) cell lines. Some of compounds showed inhibitory activities on the growth of cancer cell lines. Especially, compound 17b exhibited the most potent activity (IC50 4.6 μM) against HGC-27 as compared with the reference compound, sindaxel (IC50 10.3 μM), and could be used as a lead compound to search new chiral thiosemicarbazone derivatives as antiproliferative agents. Chirality 27:177–188, 2015. © 2014 Wiley Periodicals, Inc.

There is an increased airway inflammation in the pathogenesis of chronic obstructive pulmonary disease (COPD), and it has been suggested that there may also be problem in the apoptosis and renewal of cells. However, there are limited human airway cell studies, in particular those from larger airways such as bronchi. We cultured primary human bronchial epithelial cells (HBECs) from bronchial explants of smokers (n = 6) without COPD and smokers with COPD (n = 8). Apoptosis was studied by fluorescence activated cell sorting. qRT-PCR was used to assess mRNA expression for proteins involving apoptosis including p21(CIP1/WAF1), p53, caspase-8 and caspase-9. Although there was no difference in the rate of viable cells between cells from smokers and COPDs, the level of early apoptotic cells was significantly increased in COPD cells [mean ± standard error of mean (SEM) = 4.86 ± 3.2 %, p = 0.015] as compared to smokers (mean ± SEM = 2.71 ± 1.62 %). In contrast, the rate of late apoptotic cells was significantly decreased in COPD cells (mean ± SEM = 9.82 ± 5.71 %) comparing to smokers (mean ± SEM = 15.21 ± 5.08 %, p = 0.003). Although expression of mRNA for p21(CIP1/WAF1) and caspase-9 was similar in both groups, p53 and caspase-8 mRNA expression was significantly greater in COPD cells. These findings suggest that HBEC apoptosis is increased in COPD, and that this involves p53 and caspase-8 pathways.

Studies suggest steroid resistance in COPD patients.We cultured primary BECs from non-smokers (NS), smokers (S) and patients with COPD and incubated with dexamethasone (DEX, 0.1-100nM), N-acetylcysteine (NAC, 3.3-10mM), or c-jun N-terminal kinase inhibitor (SP600125; 3.3-33µM) under unstimulated and stimulated condition by 1ng/ml interleukin (IL)-1β.IL-6, IL-8 and granulocyte macrophage-colony stimulating factor (GM-CSF) levels,mRNA expression was assessed.DEX inhibited release of GM-CSF from un-stimulated COPD BECs (median= 1.047ng/ml) at 1nM, 100nM, and from stimulated cells (median=21.6ng/ml), at 1nM (median=15ng/ml; p

A series of thiosemicarbazones and their platinum(II) and palladium(II) complexes have been synthesized. The chemical structures of ligands and their complexes were characterized by UV–Vis, IR, 1H NMR, 13C NMR, MS spectra, elemental analysis and TGA. The antiviral and cytotoxic activities of all compounds have been tested. Results of broad antiviral evaluation showed that none of the compounds evaluated endowed with anti-DNA or -RNA virus activity at subtoxic concentrations except for the palladium complex 1b. This compound exhibited slightly selective inhibition against cytomegalovirus. The platinum complex 4a exhibited the best cytostatic activities against human cervix carcinoma. Ligands 2, 4 and 5 showed cytostatic potential. The palladium complexes were in general less cytostatic than the corresponding platinum complexes or unliganded congeners., Graphical abstract Compound 1b showed slightly inhibitory activity against HCMV at 2.9–15.3 μM. The cytostatic potency of compound 4a (IC50: 1.7 μM) was significant against HeLa cell culture. Highlights ► Some thiosemicarbazones and their Pt(II) and Pd(II) complexes were synthesized. ► All compounds were tested their in vitro antiviral and cytostatic/toxic activity. ► 1b exhibited some selective inhibition against HCMV. ► 4a showed significant cytostatic potency against HeLa cell culture.