Four series of heterocyclic compounds, namely, tetrahydro-2H-1,3,5-thiadiazine thione derivatives were synthesized in good to excellent yields and were screened for their in vitro antileishmanial activities against Leishmania major (promastigotes). Most of the compounds showed significant antileishmanial activity within the range of IC50?=?15.48–39.36?μM when compared with standard pentamidine (IC50?=?14.95?μM). The structure-activity relationship showed that N-3 and N-5 substituents have a key role against leishmanicidal activity. The ester analogues (series B) were found to have a 1.5 to 5-fold reduced activity compared to their acidic counterparts. Cytotoxicity against mammalian mouse fibroblast 3?T3 cells was also evaluated and compared between the acid and its ester analogue. The reduction of antileishmanial activity and loss of toxicity in the newly developed THTT ester derivative indicates that these compounds can be used as a template study for the production of effective antileishmanial ester prodrugs. 相似文献
A 16‐week experiment was accomplished to determine the dietary niacin requirement of fingerling Channa punctatus (6.8 ± 0.92 cm; 4.65 ± 0.46 g) by feeding seven casein‐gelatin based isonitrogenous (450 g/kg CP) and isoenergetic (18.39 kJ/g GE) diets with graded levels of niacin (0, 10, 20, 30, 40, 50 and 60 mg/kg diet) twice a day to apparent satiation to triplicate groups of fish. Significantly best absolute weight gain (AWG; 38.19 g/fish), feed conversion ratio (FCR; 1.42) and protein retention efficiency (PRE; 26.47%) were registered in fish fed 40 mg niacin/kg diet. Also, fish fed above diet exhibited maximum carcass protein. Hemoglobin (Hb), RBCs counts and hematocrit (Hct) were improved with the incremental levels of dietary niacin up to 40 mg/kg. However, liver niacin content showed the positive correlation up to 50 mg/kg niacin and then leveled off. Fingerling C. punctatus fed niacin‐free diet showed retarded growth, poor feed utilization, high mortality, difficult motion and skin haemorrhage. Broken‐line regression analysis of AWG, FCR and PRE indicated that fingerling C. punctatus require niacin in the range of 37.1–42.1, whereas that of liver niacin concentration indicated the niacin requirement at 52.3 mg/kg dry diet. 相似文献
miRNAs associate with Argonaute (AGO) proteins to silence the expression of mRNA targets by inhibiting translation and promoting deadenylation, decapping, and mRNA degradation. A current model for silencing suggests that AGOs mediate these effects through the sequential recruitment of GW182 proteins, the CCR4–NOT deadenylase complex and the translational repressor and decapping activator DDX6. An alternative model posits that AGOs repress translation by interfering with eIF4A function during 43S ribosomal scanning and that this mechanism is independent of GW182 and the CCR4–NOT complex in Drosophila melanogaster. Here, we show that miRNAs, AGOs, GW182, the CCR4–NOT complex, and DDX6/Me31B repress and degrade polyadenylated mRNA targets that are translated via scanning‐independent mechanisms in both human and Dm cells. This and additional observations indicate a common mechanism used by these proteins and miRNAs to mediate silencing. This mechanism does not require eIF4A function during ribosomal scanning. 相似文献
N-protected amino acids (Gly, Ala and Phe protected with Boc and Z groups) were reacted with sulfonamide derivatives, leading to the corresponding N-protected amino acid–sulfonamide conjugates. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of the new compounds was assessed against four human (h) isoforms, hCA I, hCA II, hCA IV and hCA XII. Among them, hCA II, IV and XII are antiglaucoma drug targets, being involved in aqueous humor secretion within the eye. Low nanomolar inhibition was measured against all four isoforms with the 20 reported sulfonamides, but no selective inhibitory profiles, except for some CA XII-selective derivatives, were observed. hCA I, II and XII were generally better inhibited by sulfonamides incorporating longer scaffolds and Gly/Ala, whereas the best hCA IV inhibitors were homosulfanilamide derivatives, incorporating Phe moieties. The amino acid–sulfonamide conjugates show good water solubility and effective hCA II, IV and XII inhibition, and may be considered as interesting candidates for antiglaucoma studies. 相似文献
Products from phototrophic dinoflagellates such as toxins or pigments are potentially important for applications in the biomedical sciences, especially in drug development. However, the technical cultivation of these organisms is often problematic due to their sensitivity to hydrodynamic (shear) stress that is a characteristic of suspension-based closed photobioreactors (PBRs). It is thus often thought that most species of dinoflagellates are non-cultivable at a technical scale. Recent advances in the development of biofilm PBRs that rely on immobilization of microalgae may hold potential to circumvent this major technical problem in dinoflagellate cultivation. In the present study, the dinoflagellate Symbiodinium voratum was grown immobilized on a Twin-Layer PBR for isolation of the carotenoid peridinin, an anti-cancerogenic compound. Biomass productivities ranged from 1.0 to 11.0 g m?2 day?1 dry matter per vertical growth surface and a maximal biomass yield of 114.5 g m?2, depending on light intensity, supplementary CO2, and type of substrate (paper or polycarbonate membrane) used. Compared to a suspension culture, the performance of the Twin-Layer PBRs exhibited significantly higher growth rates and maximal biomass yield. In the Twin-Layer PBR a maximal peridinin productivity of 24 mg m?2 day?1 was determined at a light intensity of 74 μmol m?2 s?1, although the highest peridinin content per dry weight (1.7 % w/w) was attained at lower light intensities. The results demonstrate that a biofilm-based PBR that minimizes hydrodynamic shear forces is applicable to technical-scale cultivation of dinoflagellates and may foster biotechnological applications of these abundant marine protists. 相似文献
Changes in the osmolality of the extracellular medium (ECM) affect cell volume and cellular processes such as cell migration and proliferation. Not only may high concentrations of zinc (Zn) lead to cell death by apoptosis, but Zn is also a physiological suppressor of apoptosis. The aim of our study was to examine whether Zn and regulation of extracellular osmolality had an effect on the lung cancer cell line (A549) and how to be changed in ECM according to elements and osmolality depending on incubation time and Zn application. Our study consisted of four groups: cell-free medium, ECM of cancer cell after 24 h incubation (24hECM), ECM of cancer cell after 48 h incubation (48hECM), and ECM of cancer cell after 48 h incubation with ZnCl2 (48hECM?+?Zn). ECM osmolality was measured by using osmometer, and the levels of chromium (Cr), iron (Fe), and magnesium (Mg) elements were analyzed using ICP-OES device for all groups. According to the result of the analysis, a statistically significant difference was found when osmolality and element values of ECM of 24hECM and 48hECM groups were compared with the values of the 48hECM?+?Zn group. It was observed that there was a decrease in the levels of Cr, Fe, and Mg with Zn application and incubation period in ECM. The regulation of ECM osmolality is a promising method due to biophysical effects on cancer cells. In our study, we speculated that the understanding of the effects of Zn and osmolality with the relationship between ECM and cancer cell might lead to the discovery of biophysical approaches as a novel therapeutic strategy.
New tailored Cu(II) & Zn(II) metal-based antitumor drug entities were synthesized from substituted benzothiazole o?vanillin Schiff base ligands. The complexes were thoroughly characterized by elemental analysis, spectroscopic studies {IR, 1H & 13C NMR, ESI?MS, EPR} and magnetic susceptibility measurements. The structure activity relationship (SAR) studies of benzothiazole Cu(II) & Zn(II) complexes having molecular formulas [C30H22CuN5O7S2], [C30H20Cl2CuN5O7S2], [C30H20CuF2N5O7S2], [C30H22N4O4S2Zn], [C30H20Cl2N4O4S2Zn], and [C30H20F2N5O7S2Zn], with CT?DNA were performed by employing absorption, emission titrations, and hydrodynamic measurements. The DNA binding affinity was quantified by Kb and Ksv values which gave higher binding propensity for chloro-substituted Cu(II) [C30H20Cl2CuN5O7S2] complex, suggestive of groove binding mode with subtle partial intercalation. Molecular properties and drug likeness profile were assessed for the ligands and all the Lipinski’s rules were found to be obeyed. The antimicrobial potential of ligands and their Cu(II) & Zn(II) complexes were screened against some notably important pathogens viz., E. coli, S. aureus, P. aeruginosa, B. subtilis, and C. albicans. The cytotoxicity of the complexes [C30H20Cl2CuN5O7S2], [C30H20CuF2N5O7S2], [C30H20Cl2N4O4S2Zn], and [C30H20F2N5O7S2Zn] were evaluated against five human cancer cell lines viz., MCF?7 (breast), MIA?PA?CA?2 (pancreatic), HeLa (cervix) and Hep?G2 (Hepatoma) and A498 (Kidney) by SRB assay which revealed that chloro-substituted [C30H20Cl2CuN5O7S2] complex, exhibited pronounced specific cytotoxicity with GI50 value of 4.8 μg/ml against HeLa cell line. Molecular docking studies were also performed to explore the binding modes and orientation of the complexes in the DNA helix. 相似文献