Search

In the present study, a series of NSAIDs-Se derivatives include selenocyanates and diselenides were synthesized and characterized, their anticancer activities against the human cancer cell lines SW480, HeLa, A549, and HepG2 were determined. Interestingly, most of the new compounds showed active in reducing the viability of different cancer lines. Compounds 1a and 1m exhibited higher promising activities than other derivatives. As the most active compound 1a showed IC50 values lower than 20 μM against the four cancer cell lines, particularly against SW480 with IC50 values below 10 μm, it shows the potential to be a promising molecular chemotherapeutic agent for colorectal cancer. [ABSTRACT FROM AUTHOR]

In the present study on the development of new anticonvulsants, twelve new aryl sulfonyl semicarbazide derivatives were synthesized and tested for anticonvulsant activity using maximal electroshock (MES), subcutaneous pentylenetetrazole screens. Their neurotoxicity was determined by the rotorod test. The most active compound 5i showed the MES-induced seizures with ED value of 7.3 mg/kg and TD value of 402.3 mg/kg after intraperitoneally injection to mice, which provided compound 5i with a protective index (TD/ED) of 55.1 in the MES test. [ABSTRACT FROM AUTHOR]

Recent studies identified polychlorinated biphenyl (PCB) sulfate esters as a major product of PCB metabolism. Since hydroxy-PCBs (HO-PCBs), the immediate precursors of PCB sulfates and important contributors to PCB toxicity, were shown to have estrogenic activity, we investigated the estrogenicity/androgenicty of a series of PCB sulfate metabolites. We synthesized the five possible structural sulfate monoester metabolites of PCB 3, a congener shown to be biotransformed to sulfates, a sulfate ester of the paint-specific congener PCB 11, and sulfate monoesters of two HO-PCBs reported to interact with sulfotransferases (PCB 39, no ortho chlorines, and PCB 53, 3 ortho chlorines). We tested these PCB sulfates and 4′-HO-PCB 3 as positive control for estrogenic, androgenic, anti-estrogenic, and anti-androgenic activity in the E- and A-screen with human breast cancer MCF7-derived cells at 100 μM-1 pM concentrations. Only 4′-HO-PCB 3 was highly cytotoxic at 100 μM. We observed structure-activity relationships: compounds with a sulfate group in the chlorine-containing ring of PCB 3 (2PCB 3 and 3PCB 3 sulfate) showed no interaction with the estrogen (ER) and androgen (AR) receptor. The 4′-HO-PCB 3 and its sulfate ester had the highest estrogenic effect, but at 100-fold different concentrations, i.e., 1 and 100 μM, respectively. Four of the PCB sulfates were estrogenic (2′PCB 3, 4′PCB 3, 4′PCB 39, and 4′PCB 53 sulfates; at 100 μM). These sulfates and 3′PCB 3 sulfate also exhibited anti-estrogenic activity, but at nM and pM concentrations. The 4′PCB 3 sulfate ( para-para′ substituted) had the strongest androgenic activity, followed by 3′PCB 3, 4′PCB 53, 4PCB11, and 4PCB 39 sulfates and the 4′HO-PCB 3. In contrast, anti-androgenicity was only observed with the two compounds that have the sulfate group in ortho- or meta- position in the second ring (2′PCB 3 and 3′PCB 3 sulfate). No dose-response was observed in any screen, but, with exception of estrogenic activity (only seen at 100 μM), endocrine activity was often displayed at several concentrations and even at 1 pM concentration. These data suggest that sulfation of HO-PCBs is indeed reducing their cytotoxicity and estrogenicity, but may produce other endocrine disruptive activities at very low concentrations. [ABSTRACT FROM AUTHOR]

In this study, sixteen new 5,5-cyclopropanespirohydantoin derivatives were synthesized and tested for anticonvulsant activity using maximal electroshock (MES), subcutaneous pentylenetetrazole screens. Their neurotoxicity was determined by the rotarod test. Two compounds 7f and 7n showed promising anticonvulsant activities in both models employed for anticonvulsant evaluation. The most active compound 7f showed the MES-induced seizures with ED value of 8.5 mg/kg and TD value of 381.7 mg/kg after intraperitoneally injection to mice, which provided compound 7f with a protective index (TD/ED) of 44.9 in the MES test. [ABSTRACT FROM AUTHOR]