Química Medicinal

Sulphonamides embrace a sublime class of drugs with various biological activities. Since the discovery of E7010 in 1992, several sulphonamides as anti-cancer drug candidates have been identified. Herein, a new series of 5-chloro- 2-methoxy-N-(4-sulphamoylphenyl)benzamide derivatives was synthesised, and their anti-proliferative activity was evaluated against human ovarian cancer (A2780) and colon cancer (HCT-116) cell lines. As one of the most potent antiproliferative agents, compound 4j was further tested against a panel of cancer cell lines revealing that human pancreatic carcinoma (MIA PaCa-2) displayed the highest sensitivity. Cellular mechanistic studies on MIA PaCa-2 cells showed that 4j arrested the G2/M cell cycle and induced apoptosis.

Background: Monocytes and granulocytes, activated by contact with hemodialysis membranes, generate increased cytokine secretion, an important key in pathogenesis of anemia and erythropoietin (rHuEPO) resistance. We aimed to examine the correlation of IL-17 and pro-hepcidin with anemia of chronic kidney disease (CKD) patients treated with hemodialysis(HD).

Method: 69 HD patients were included. Exclusion criteria were: neoplasia, acute infections, blood loss, absolute iron deficiency. IL-17 and pro-hepcidin were determined. Hemoglobin, ferritin, transferrin and transferrin saturation were measured. rHuEPO responsiveness index was calculated. A poor response to rHuEPO was defined as rHuEPO responsiveness index>200.

Results: Mean level of IL-17 was 33.3 ± 5.1 pg/ml and pro-hepcidin was 336.6 ± 23.7 pg/ml. IL-17 and pro-hepcidinnegatively correlated with hemoglobin (R0.503, p<0.001and R0.693, p<0.001) and with transferrin saturation (R0.306, p=0.01; R0.455, p=0.002) and positively correlated with rHuEPO responsiveness index (R0.416, p<0.001; R0.674, p<0.001). Patients with rHuEPO index>200 had higher pro-hepcidin (432.5 ± 25 vs. 157.5 ± 12 pg/ml, p<0.001), increased IL-17 (27 ± 1.9 vs. 4.9 ± 0.3 pg/ml, p<0.001), and lower iron biodisponibility (transferrin saturation 18 ± 1.6% vs.31 ± 1.2%; p<0.001) than those with rHuEPO responsiveness index<200. IL-17 positively correlated with prohepcidin (R0.454, p<0.001).

Conclusion: High levels of IL-17 and pro-hepcidin are both correlated with low hemoglobin, poor response to rHuEPO and decreased iron biodisponibility in hemodialysis patients.

A series of potential bioactive compounds, N-(4-(aryl)-2-thioxo-1,3-thiazol-3(2H)-yl) pyridine-4-carboxamide has been synthesized and screened for antibacterial, antifungal, anti-inflammatory activity by minimum inhibitory concentration and protein denaturation method respectively. The compounds IIc and IIj were found to be broad spectrum antimicrobial agents at minimum inhibitory concentration value against E. coli, K. pneumonia, S. aureus, B. subtilis, A. nigar, and S. cerevisiae respectively. In anti-inflammatory activity, compounds IIc, IIf, IIh, and IIj at 100 mg/ml and compound IIl at 200 mg/ml were found significant active agent.

The major targeting strategies that were used for the delivery of therapeutics which are explored for many of the reported nanoemulsions suggest the great potential of targeted delivery to revolutionize cancer treatment. Targeted delivery via selective cellular markers can potentially increase the efficacy and reduce the toxicity of therapeutic agents. The effectiveness of a cancer therapeutic device is measured by its ability to reduce and eliminate tumors without damaging healthy tissue. Therefore, a distinct capacity to target tumors is essential in the success of the therapeutic device. An increased site specificity and internalization can improve the efficacy of treatment and decrease the possibility of the serious side effects that cancer patients often experience. The ultimate goal of cancer therapeutics is to increase the survival time and the quality of life of the patient. Nanoemulsions offer major improvements in therapeutics through site specificity, their ability to escape from multi-drug resistance and the efficient delivery of an agent. There is large overlap between the divisions which reflect the heterogeneity of tumor biology and the large potential for multiple targeting schemes using different ligands. The objective of this review is to outline current major cancer targets for nanoemulsions and give insight into the direction of the field.

Acetylated trisglucosydic derivative of 2,3,5,6,8-pentahydroxy-7-ethyl-1,4-naphthoqinone (natural sea urchin pigment echinochrome), compound U-133, was synthesized. The effect of U-133 upon mouse Ehrlich ascitic carcinoma(EAC) cells in vitro and its antitumor activity in vivo was investigated. The synthesized U-133 did not display the pronounced cytotoxicity against EAC cells in the concentrations up to 80 μM. In non-cytotoxic concentration of 5 μM U-133 significantly induced Hsp70 expression in cancer cells and enhanced cell-mediated cytotoxicity of mouse splenocytes against EAC cells. The administration of U-133 in dosage of 100 mg/kg in carcinoma bearing mice resulted in significant inhibition of tumor growth and increase in mouse lifespan.

Objective: In view of the high INH resistance, we conducted in vitro drug susceptible test of Isoniazid (INH) and Parasal (PAS) and Pasiniazid (PA) to determine the cross-resistance of the three drugs.

Method: The proportion method on Lo¨wenstein–Jensen (L–J) medium was used to conduct antimycobacterial susceptibility testing of INH and PAS and PA to one hundred and ninety-seven clinical isolates of, including multidrugresistant isolates.

Results: For INH-resistant isolates, PA sensitive rate was as high as 73.6%. The three PAS-resistant isolates were all susceptible to PA. 92% of the isolates resistant to INH and PAS simultaneously were resistant to PA. Most of the isolates susceptible to INH and PAS were also susceptible to PA. More than half of the MDR strains are still sensitive to PA. Almost all of the seventy PA-resistant isolates were also resistant to INH except one isolate. However, 34.3% of the seventy PA-resistant isolates were susceptible to PAS. For MDR isolates in this experiment, PA resistant rate was 46.2%.

Conclusion: PA showed lower susceptibility to the isolate resistant to INH and PAS simultaneously. PAS has strong anti-TB effect. INH is not recommended for the PA-resistant isolates. For single INH resistant cases or MDR cases, we can consider using PA instead of INH.

A number of novel 3-arylilidene and 3-arylimine-2-oxindole derivatives were synthesized, and their Src kinase inhibitory activities and antiproliferative activities were evaluated. Several compounds exhibited Src kinase inhibitory activitywith IC50 values in the range of 5.3 to 211.8 μM. Compound b11 in 3-arylimine-2-oxindoles showed IC50 values of 5.3 μM against Src kinase. Compounds a8, a20, a38, and b15 showed consistently>50% proliferation inhibition against all three cancer celllines at a concentration of 50 μM.

Dexlansoprazole is an outstandingproton pump inhibitors, which is a chiral sulfoxide. We firstly report determination of the absolute configuration (AC) of dexlansoprazole by the combination of experimental and calculated optical rotation (OR), electronic circular dichroism (ECD) and 13C-NMR. The high agreement between theoretical and experimental data illustrates that this method would be used to determine the absolute configuration of chiral sulfoxide.

Schistosomiasis has influence on people’s security and daily life significantly, while cercarial stage of the schistosome life-cycle is the only infectious period. To detect cercarial efficiently, we synthesized rare-earth upconversion nanophosphors UCs-Ni loaded with niclosamide. The fluorescenceof UCs-Ni was demonstrated by the fluorescence emission spectra. The cell imaging test illustrated that UCs-Ni was biocompatible, cell-permeable and suitable for cercariae imaging. When it has been utilized for cercariae imaging, we found that the UCs-Ni could penetrate into cercariae.