In vitro antitubercular and antimicrobial activities of 1-substituted quinoxaline-2,3(1H,4H)-diones

1-((Substituted)methyl)quinoxaline-2,3(1H,4H)-dione (2a–e) and 1-((substituted)acryloyl)quinoxaline-2,3(1H,4H)-dione (4a–c) were synthesized from quinoxaline-2,3(1H,4H)-dione 1 and evaluated for their antimicrobial activities. Results of the antitubercular screening against Mycobacterium tuberculosis H₃₇Rv showed that the compounds 2b, 3, and 4a were the most effective, with minimum inhibitory concentrations of 8.012, 8.561, and 8.928 μg/ml, respectively. All the compounds exhibited significant antibacterial and considerable antifungal activities.     

Antitermitic quinones from Diospyros sylvatica

Six quinones were isolated from the chloroform extract of the roots of Diospyros sylvatica and identified as 2-methyl-anthraquinone, plumbagin, diosindigo, diospyrin, isodiospyrin and microphyllone. The effect of the root extract on the orientation and survival of the subterranean termite, Odontotermes obesus was tested. In addition, four of these quinones were tested on the survival of the subterranean termite. In a direct-choice experiment, exposure to an extract-treated filter disc had a significantly repellent effect over the solvent-treated filter disc. The no-choice experiment revealed the toxic property of the extract as well as the tested quinones and showed high mortality of the O. obesus workers after 48 h on forced exposure. The major termiticidal components identified were plumbagin, isodiospyrin and microphyllone while diospyrin was not toxic to termites at the concentration tested. All the quinones are reported for the first time from D. sylvatica.     

Cytotoxic benzil and coumestan derivatives from Tephrosia calophylla

A benzil, calophione A, 1-(6′-Hydroxy-1′,3′-benzodioxol-5′-yl)-2-(6″-hydroxy-2″-isopropenyl-2″,3″-dihydro-benzofuran-5″-yl)-ethane-1,2-dione and three coumestan derivatives, tephcalostan B, C and D were isolated from the roots of Tephrosia calophylla. Their structures were deduced from spectroscopic data, including 2D NMR ¹H-¹H COSY and ¹³C-¹H COSY experiments. Compounds were evaluated for cytotoxicity against RAW (mouse macrophage cells) and HT-29 (colon cancer cells) cancer cell lines and antiprotozoal activity against various parasitic protozoa. Calophione A exhibited significant cytotoxicity with IC₅₀ of 5.00 (RAW) and 2.90 μM (HT-29), respectively.     

Antiprotozoal and cytotoxic naphthalene derivatives from Diospyros assimilis

Chemical investigation of the roots of Diospyros assimilis had led to the isolation and characterization of six naphthalene derivatives, two 2-naphthaldehyes, namely 4-hydroxy-3,5-dimethoxy-2-naphthaldehyde 1, 4-hydroxy-5-methoxy-2-naphthaldehye 2, its related isomer 5-hydroxy-4-methoxy-2-naphthaldehyde 3 and three commonly occurring naphthoquinones, diospyrin 4, 8'-hydroxyisodiospyrin 5 and the simple monomer, plumbagin 6. Their chemical structures were established by detailed NMR investigations including 1H and 13C NMR, HSQC, HMBC and NOESY experiments. In addition, the naphthalene derivatives 1-5 were evaluated for their in vitro antiprotozoal activity against protozoan parasites belonging to the genera Trypanosoma, Leishmania and Plasmodium. Among the tested compounds, naphthaldehyde 1 showed moderate inhibition of the growth of the parasites, T. brucei, T. cruzi, L. donovani with IC50 values of 19.82, 12.28 and 38.78 microM and displayed cytotoxicity towards rat skeletal myoblasts (L-6 cells) with IC50 of 174.94 microM, while 2 and 3 were found to be comparatively less active to 1. The dimeric quinones 4 and 5 exhibited good activity against T. brucei and L. donovani with IC50 of 1.12 and 8.82 microM and 12.94 and 16.66 microM respectively.     

CuZn-superoxide dismutase in human thymus: immunocytochemical localisation and secretion in thymus-derived epithelial and fibroblast cell lines

CuZn-superoxide dismutase (SOD) plays a key role in mediating the cellular response to oxidative stress. Its expression in normal thymus was investigated by immunohistochemical techniques and CD3-, CD68- and cytokeratin-specific staining, in order to identify thymocytes, macrophages and epithelial components. Immunocytochemical studies showed an overall CuZn-SOD thymic distribution with a prevailing concentration within thymic medulla. The analysis of CuZn-SOD release by thymus-derived epithelial and fibroblast cell lines showed the ability of both cell lines to release the anti-oxidant enzyme, especially in the presence of stress conditions as represented by serum and nutrient deprivation. These data suggest that CuZn-SOD could be a relevant antioxidant paracrine molecule in human thymus.     

A new perspective on the role of CuZn superoxide dismutase (SOD1)

The CuZn superoxide dismutase (SOD1), a member of a group of isoenzymes involved in the scavenger of superoxide anions, is a dimeric carbohydrate free protein, mainly localized in the cytosol. The reactive oxygen species (ROS) are involved in many pathophysiological events correlated with mutagenesis, cancer, degenerative processes and aging. In the first part of this mini-review the well known role of SOD1 and ROS are briefly summarized. Following, a potential novel biological action that SOD1 could exert is described, based on the recent researches demonstrating the secretion of this enzyme in many cellular lines. Moreover, the role of impaired mutant SOD1 secretion, associated with cytoplasmic toxic inclusion, which occurs in familial amyotrophic lateral sclerosis (ALS), is summarized. In addition, a depolarization-dependent release of SOD1 in pituitary GH3 cells and in rat synaptosomes through a calcium and SNARE-dependent mechanism is reported.