Molecular docking, synthesis, characteristics and preliminary cytotoxic study of new coumarin-sulfonamide derivatives as histone deacetylase inhibitors.

OBJECTIVE: Aim: To evaluate the cytotoxic activity of newly synthesized a series of novel HDAC inhibitors comprising sulfonamide as zinc binding group and Coumarin as cap groups. PATIENTS AND METHODS: Materials and Methods: The utilization of sulfonamide as zinc binding group and Coumarin as cap groups known to possess antitumor activity in the designed of new histone deacetylase inhibitors and using the docking and MTT assay to evaluate the compounds. RESULTS: Results: Four compounds have been synthesized and characterized successfully by ART-FTIR, NMR and ESI-Ms. The synthesized compound assessed for their cytotoxic activity against hepatoblastoma HepG2 (IC50, I=0.094, II=0.040, III=0.032, IV=0.046, SAHA=0.141) and human colon adenocarcinoma MCF-7 (IC50, I=0.135, II=0.050, III= 0.065, IV=0.059, SAHA=0.107). The binding mode to the active site of [HDAC6] were determined by docking study which give results that they might be good inhibitors for [HDAC6]. CONCLUSION: Conclusions: The synthesized compounds (I, II, III and IV) showed a comparable cytotoxic result with FDA approved drug (SAHA) toward HepG2 and MCF-7 cancer cell lines and their docking analysis provided a preliminary indication that they are viable [HDAC6] candidates.

Design, synthesis, insilco study and biological evaluation of new isatin-sulfonamide derivatives by using mono amide linker as possible as histone deacetylase inhibitors.

OBJECTIVE: Aim: To evaluate the cytotoxic activity of newly synthesized a series of novel HDAC inhibitors comprising sulfonamide as zinc binding group and Isatin derivatives as cap group joined by mono amide linker as required to act as HDAC inhibitors. PATIENTS AND METHODS: Materials and Methods: The utilization of sulfonamide as zinc binding group joined by N-alkylation reaction with ethyl-bromo hexanoate as linker group that joined by amide reaction with Isatin derivatives as cap groups which known to possess antitumor activity in the designed of new histone deacetylase inhibitors and using the docking and MTT assay to evaluate the compounds. RESULTS: Results: Four compounds have been synthesized and characterized successfully by ART-FTIR, NMR and ESI-Ms. the compounds were synthesized and characterized by successfully by ART-FTIR, NMR and ESI- Ms. Assessed for their cytotoxic activity against human colon adenocarcinoma MCF-7 (IC50, I=105.15, II=60.00, III=54.11, IV=56.57, vorinostat=28.41) and hepatoblastoma HepG2 (IC50, I=63.91, II=135.18, III=118.85, IV=51.46, vorinostat=37.50). Most of them exhibited potent HDAC inhibitory activity and significant cytotoxicity. CONCLUSION: Conclusions: The synthesized compounds (I, II, III and IV) showed cytotoxicity toward MCF-7 and HepG2 cancer cell lines and their docking analysis provided a preliminary indication that they are viable [HDAC6] candidates.

Are programmed cell death protein-1 and Angiopoietins-2 effective biomarkers for detection the severity of psoriatic patients?

BACKGROUND: Early detection of psoriasis is still an open discussion. Psoriatic lesions are characterized by red/scaly plaques affecting different body-sites. OBJECTIVES: To evaluate the levels of programmed cell death protein-1(PD-1) and Angiopoietins-2(Ang-2) in serum, lesional, and perilesional of psoriatic patients and correlate them with controls and disease severity. SUBJECTS AND METHODS: Serum samples were obtained from 40 participants subdivided equally into psoriatic and healthy controls, 4 mm punch_biopsy equally from lesional and perilesional skin of individuals. PD-1/ANG-2 ELISA kits were used for determining the serum and tissue levels among groups. RESULTS: Serum and tissue levels of PD-1 and Ang-2 were overexpressed in psoriatic patients compared with controls. There was a statistical difference between patients and controls in level of PD-1(serum and tissue) with p-value 0.006 and 0.0001, respectively. There was a statistical difference between both groups for ANG-2(serum and tissue) with p-value 0.03 and 0.0001, respectively. There were positive correlations between PASI score and PD-1 in tissue (r = 0.467, p = 0.038). Also, positive correlation between the level of PD-1 in serum and tissue (r = 0.369, p = 0.019), the serum levels of PD-1 and ANG-2 (r = 0.78, p > 0.0001), PD-1 and Ang-2 in tissue (r = 0.583,p = 0.0001) were detected. CONCLUSION: PD-1 and ANG-2 can be highly recommended to determine the severity of psoriasis.

Palivizumab prophylaxis against respiratory syncytial virus infection in patients younger than 2 years of age with congenital heart disease.

BACKGROUND: Respiratory syncytial virus (RSV) is a viral pathogen that causes annual epidemics of lower respiratory tract infection with substantial morbidity and mortality in young children, especially those with congenital heart disease (CHD). Palivizumab is the only immunoprophylaxis therapy approved for RSV infection in infants with hemodynamically significant acyanotic or cyanotic CHD. OBJECTIVE: Identify the compliance rate with vaccination and study the effect of RSV vaccination on hospital admissions. DESIGN: Retrospective descriptive study. SETTING: Cardiac center. PATIENTS AND METHODS: Patient data was obtained from outpatient clinic records, inpatient records, and a surgical database for the period from October 2010 to March 2016. Infants with hemodynamically significant CHD, cyanotic CHD and moderate-to-severe pulmonary hypertension were included in the study. Palivizumab 15/mg/kg was given monthly starting from October, the usual beginning of the epidemic season, with five doses in the first season and six doses in the remaining season scheduled for administration. Patients were interviewed at every clinic visit for any side effects during the previous month, occurrence of any RSV infection and any hospital admission. Selection criteria included RSV vaccination and absence of RSV disease. Patients were excluded if they had RSV infection or a repaired cardiac lesion. MAIN OUTCOME MEASURES: Compliance rate, hospital admission frequency and period of stay. SAMPLE SIZE: 530 during six seasons of RSV epidemics. RESULTS: Fourteen patients (2.6%) developed RSV infection and 13 (2.5%) required hospital admission, but only one patient (0.1%) needed intensive care admission. There were no deaths related to RSV infection; however 11 patients died due to causes unrelated to RSV infection. The average compliance rate was 97%. CONCLUSION: Palivizumab was well tolerated and effective in the prophylaxis of severe RSV infection in children with CHD. As in other studies of palivizumab prophylaxis, we observed a reduction in hospital admissions. LIMITATIONS: Retrospective design. CONFLICT OF INTEREST: None.