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Novel N-substituted 5-aminosalicylamides as dual inhibitors of cyclooxygenase and 5-lipoxygenase enzymes: Synthesis, biological evaluation and docking study.

Research Abstract
Three new series of 5-aminosalicylic acid derivatives; series I (14, 16-18), series II (19-30) and series III (31-41) were synthesized as potential dual COX-2/5-LOX inhibitors. Their chemical structures were confirmed using spectroscopic tools including IR, 1H NMR, 13C NMR, mass spectroscopy and elemental analyses. The anti-inflammatory activity for all target compounds was evaluated in vivo using carrageenan-induced paw edema. Compound 36 showed the highest anti-inflammatory activity (114.12%) relative to reference drug indomethacin at 4 h interval. Selected derivatives were evaluated in vitro to inhibit ovine COX-1, human recombinant COX-2 and 5-LOX enzymes. Compounds 34 &35 exhibited significant COX-2 inhibition (IC50 = 0.10 µM) with significant COX-2 selectivity indices (SI = 135 & 145 respectively) approximate to celecoxib (IC50 = 0.049 µM, SI = 308.16) and exceeding indomethacin (IC50 = 0.51 µM, SI = 0.08). Interestingly, all compounds showed superior 5-LOX inhibitory activity about 2-5 times relative to zileuton. Compound 16 was the superlative 5-LOX inhibitor that revealed (IC50 = 3.41 µM) relative to zileuton (IC50 = 15.6 µM). Compounds 34, 35, 36 and 41 showed significant dual COX-2/5-LOX inhibitions. The gastric ulcerogenic effect of compound 36 was examined on gastric mucosa of albino rats and they showed superior GI safety profile compared with indomethacin. Molecular docking studies of the compounds into the binding sites of COX-1, COX-2 and 5-LOX allowed us to shed light on the binding mode of these novels dual COX and 5-LOX inhibitors.
Research Authors
El-Nagar MKS, Abdu-Allah HHM, Salem OIA, Kafafy AN, Farghaly HSM.
Research Journal
Bioorg Chem
Research Pages
80-93
Research Publisher
Elsevier
Research Rank
1
Research Vol
6;78
Research Website
NULL
Research Year
2018

Novel N-substituted 5-aminosalicylamides as dual inhibitors of cyclooxygenase and 5-lipoxygenase enzymes: Synthesis, biological evaluation and docking study.

Research Abstract
Three new series of 5-aminosalicylic acid derivatives; series I (14, 16-18), series II (19-30) and series III (31-41) were synthesized as potential dual COX-2/5-LOX inhibitors. Their chemical structures were confirmed using spectroscopic tools including IR, 1H NMR, 13C NMR, mass spectroscopy and elemental analyses. The anti-inflammatory activity for all target compounds was evaluated in vivo using carrageenan-induced paw edema. Compound 36 showed the highest anti-inflammatory activity (114.12%) relative to reference drug indomethacin at 4 h interval. Selected derivatives were evaluated in vitro to inhibit ovine COX-1, human recombinant COX-2 and 5-LOX enzymes. Compounds 34 &35 exhibited significant COX-2 inhibition (IC50 = 0.10 µM) with significant COX-2 selectivity indices (SI = 135 & 145 respectively) approximate to celecoxib (IC50 = 0.049 µM, SI = 308.16) and exceeding indomethacin (IC50 = 0.51 µM, SI = 0.08). Interestingly, all compounds showed superior 5-LOX inhibitory activity about 2-5 times relative to zileuton. Compound 16 was the superlative 5-LOX inhibitor that revealed (IC50 = 3.41 µM) relative to zileuton (IC50 = 15.6 µM). Compounds 34, 35, 36 and 41 showed significant dual COX-2/5-LOX inhibitions. The gastric ulcerogenic effect of compound 36 was examined on gastric mucosa of albino rats and they showed superior GI safety profile compared with indomethacin. Molecular docking studies of the compounds into the binding sites of COX-1, COX-2 and 5-LOX allowed us to shed light on the binding mode of these novels dual COX and 5-LOX inhibitors.
Research Authors
El-Nagar MKS, Abdu-Allah HHM, Salem OIA, Kafafy AN, Farghaly HSM.
Research Journal
Bioorg Chem
Research Pages
80-93
Research Publisher
Elsevier
Research Rank
1
Research Vol
6;78
Research Website
NULL
Research Year
2018

Novel N-substituted 5-aminosalicylamides as dual inhibitors of cyclooxygenase and 5-lipoxygenase enzymes: Synthesis, biological evaluation and docking study.

Research Abstract
Three new series of 5-aminosalicylic acid derivatives; series I (14, 16-18), series II (19-30) and series III (31-41) were synthesized as potential dual COX-2/5-LOX inhibitors. Their chemical structures were confirmed using spectroscopic tools including IR, 1H NMR, 13C NMR, mass spectroscopy and elemental analyses. The anti-inflammatory activity for all target compounds was evaluated in vivo using carrageenan-induced paw edema. Compound 36 showed the highest anti-inflammatory activity (114.12%) relative to reference drug indomethacin at 4 h interval. Selected derivatives were evaluated in vitro to inhibit ovine COX-1, human recombinant COX-2 and 5-LOX enzymes. Compounds 34 &35 exhibited significant COX-2 inhibition (IC50 = 0.10 µM) with significant COX-2 selectivity indices (SI = 135 & 145 respectively) approximate to celecoxib (IC50 = 0.049 µM, SI = 308.16) and exceeding indomethacin (IC50 = 0.51 µM, SI = 0.08). Interestingly, all compounds showed superior 5-LOX inhibitory activity about 2-5 times relative to zileuton. Compound 16 was the superlative 5-LOX inhibitor that revealed (IC50 = 3.41 µM) relative to zileuton (IC50 = 15.6 µM). Compounds 34, 35, 36 and 41 showed significant dual COX-2/5-LOX inhibitions. The gastric ulcerogenic effect of compound 36 was examined on gastric mucosa of albino rats and they showed superior GI safety profile compared with indomethacin. Molecular docking studies of the compounds into the binding sites of COX-1, COX-2 and 5-LOX allowed us to shed light on the binding mode of these novels dual COX and 5-LOX inhibitors.
Research Authors
El-Nagar MKS, Abdu-Allah HHM, Salem OIA, Kafafy AN, Farghaly HSM.
Research Journal
Bioorg Chem
Research Pages
80-93
Research Publisher
Elsevier
Research Rank
1
Research Vol
6;78
Research Website
NULL
Research Year
2018

Experience of a Tertiary-Level Urology Center in the Clinical Urological Events of Rare and Very Rare Incidence. I. Surgical Never Events: 2. Intracorporeally-Retained Urological Surgical Items

Research Abstract
Objective: Presentation of our center's experience in the management of intracorporeally-retained urological surgical items. Materials and Methods: Retrospective search of our center's data for cases of retained surgical items during the period July 2006 to June 2016. Each case was studied for the demographic and clinical variables including types, presentation, and management. Results: Out of more than 55,000 different urological interventions, only 39 cases (28 males and 11 females) had retained surgical items. Urolithiasis-related urological subspecialties were more involved than others. Forgotten items and technically-retained items occurred in 38.5 and 61.5% of cases, respectively, and were immediately discovered or discovered up to 10 years later. Material types were textiles, biosynthetics, and metallics in 31, 51, and 18%, respectively. Possible predisposing factors included complex surgeries, emergent intraoperative events, and extra approaches. Occurrences of retained surgical items before and after implemented corrective actions were 74.6 and 25.4%, respectively. All the final outcomes were either short- or long-term harm without deaths, organ losses, or permanent disabilities. Conclusion: Retained urological surgical items are surgical never events that result from forgetfulness or technical surgical human errors. Their sequels can be potentially fatal, but they are preventable and can be significantly reduced.
Research Authors
Rabea Ahmed Gadelkareem
Research Department
Research Journal
Current Urology
Research Pages
151-156
Research Publisher
KARGER
Research Rank
1
Research Vol
Vol 11, No 3
Research Website
https://doi.org/10.1159/000447210
Research Year
2018

Laparoscopic excision of a large symptomatic and kidney-displacing adrenal myelolipoma: A case report

Research Abstract
Introduction Adrenal myelolipoma is a rare tumor. Traditionally, open surgical adrenalectomy was the standard treatment for symptomatic myelolipoma. However, laparoscopic excision is a promising alternative approach. Observation A 38-year-old obese male patient presented with right loin pain of many months duration. Imaging studies revealed a large well-defined high fat content right adrenal mass displacing the right kidney. Adrenal tumor markers were within normal suggesting a non-functioning lesion. In spite of some technical difficulties and adjustments, laparoscopic excision was done, successfully, with uneventful recovery and short convalescence. Histopathological examination described mature adipose tissue with myeloid cells and confirmed the diagnosis of adrenal myelolipoma. Conclusions Laparoscopic excision of large adrenal myelolipoma may indicate some technical adjustments, but it seems to be a feasible and advantageous approach even in obese patients.
Research Authors
R.A. Gadelkareem, M.M. Khalil, N. Mohammeda, R. Makboul, F.A. Badary
Research Department
Research Journal
African Journal of Urology
Research Member
Research Pages
63-66
Research Publisher
Elsevier
Research Rank
1
Research Vol
Vol 24 - No 1
Research Website
https://doi.org/10.1016/j.afju.2017.07.004
Research Year
2018

Laparoscopic excision of a large symptomatic and kidney-displacing adrenal myelolipoma: A case report

Research Abstract
Introduction Adrenal myelolipoma is a rare tumor. Traditionally, open surgical adrenalectomy was the standard treatment for symptomatic myelolipoma. However, laparoscopic excision is a promising alternative approach. Observation A 38-year-old obese male patient presented with right loin pain of many months duration. Imaging studies revealed a large well-defined high fat content right adrenal mass displacing the right kidney. Adrenal tumor markers were within normal suggesting a non-functioning lesion. In spite of some technical difficulties and adjustments, laparoscopic excision was done, successfully, with uneventful recovery and short convalescence. Histopathological examination described mature adipose tissue with myeloid cells and confirmed the diagnosis of adrenal myelolipoma. Conclusions Laparoscopic excision of large adrenal myelolipoma may indicate some technical adjustments, but it seems to be a feasible and advantageous approach even in obese patients.
Research Authors
R.A. Gadelkareem, M.M. Khalil, N. Mohammeda, R. Makboul, F.A. Badary
Research Department
Research Journal
African Journal of Urology
Research Pages
63-66
Research Publisher
Elsevier
Research Rank
1
Research Vol
Vol 24 - No 1
Research Website
https://doi.org/10.1016/j.afju.2017.07.004
Research Year
2018

Laparoscopic excision of a large symptomatic and kidney-displacing adrenal myelolipoma: A case report

Research Abstract
Introduction Adrenal myelolipoma is a rare tumor. Traditionally, open surgical adrenalectomy was the standard treatment for symptomatic myelolipoma. However, laparoscopic excision is a promising alternative approach. Observation A 38-year-old obese male patient presented with right loin pain of many months duration. Imaging studies revealed a large well-defined high fat content right adrenal mass displacing the right kidney. Adrenal tumor markers were within normal suggesting a non-functioning lesion. In spite of some technical difficulties and adjustments, laparoscopic excision was done, successfully, with uneventful recovery and short convalescence. Histopathological examination described mature adipose tissue with myeloid cells and confirmed the diagnosis of adrenal myelolipoma. Conclusions Laparoscopic excision of large adrenal myelolipoma may indicate some technical adjustments, but it seems to be a feasible and advantageous approach even in obese patients.
Research Authors
R.A. Gadelkareem, M.M. Khalil, N. Mohammeda, R. Makboul, F.A. Badary
Research Department
Research Journal
African Journal of Urology
Research Pages
63-66
Research Publisher
Elsevier
Research Rank
1
Research Vol
Vol 24 - No 1
Research Website
https://doi.org/10.1016/j.afju.2017.07.004
Research Year
2018

Laparoscopic excision of a large symptomatic and kidney-displacing adrenal myelolipoma: A case report

Research Abstract
Introduction Adrenal myelolipoma is a rare tumor. Traditionally, open surgical adrenalectomy was the standard treatment for symptomatic myelolipoma. However, laparoscopic excision is a promising alternative approach. Observation A 38-year-old obese male patient presented with right loin pain of many months duration. Imaging studies revealed a large well-defined high fat content right adrenal mass displacing the right kidney. Adrenal tumor markers were within normal suggesting a non-functioning lesion. In spite of some technical difficulties and adjustments, laparoscopic excision was done, successfully, with uneventful recovery and short convalescence. Histopathological examination described mature adipose tissue with myeloid cells and confirmed the diagnosis of adrenal myelolipoma. Conclusions Laparoscopic excision of large adrenal myelolipoma may indicate some technical adjustments, but it seems to be a feasible and advantageous approach even in obese patients.
Research Authors
R.A. Gadelkareem, M.M. Khalil, N. Mohammeda, R. Makboul, F.A. Badary
Research Department
Research Journal
African Journal of Urology
Research Pages
63-66
Research Publisher
Elsevier
Research Rank
1
Research Vol
Vol 24 - No 1
Research Website
https://doi.org/10.1016/j.afju.2017.07.004
Research Year
2018

Laparoscopic excision of a large symptomatic and kidney-displacing adrenal myelolipoma: A case report

Research Abstract
Introduction Adrenal myelolipoma is a rare tumor. Traditionally, open surgical adrenalectomy was the standard treatment for symptomatic myelolipoma. However, laparoscopic excision is a promising alternative approach. Observation A 38-year-old obese male patient presented with right loin pain of many months duration. Imaging studies revealed a large well-defined high fat content right adrenal mass displacing the right kidney. Adrenal tumor markers were within normal suggesting a non-functioning lesion. In spite of some technical difficulties and adjustments, laparoscopic excision was done, successfully, with uneventful recovery and short convalescence. Histopathological examination described mature adipose tissue with myeloid cells and confirmed the diagnosis of adrenal myelolipoma. Conclusions Laparoscopic excision of large adrenal myelolipoma may indicate some technical adjustments, but it seems to be a feasible and advantageous approach even in obese patients.
Research Authors
R.A. Gadelkareem, M.M. Khalil, N. Mohammeda, R. Makboul, F.A. Badary
Research Department
Research Journal
African Journal of Urology
Research Pages
63-66
Research Publisher
Elsevier
Research Rank
1
Research Vol
Vol 24 - No 1
Research Website
https://doi.org/10.1016/j.afju.2017.07.004
Research Year
2018

Extra-hepatic infection of hepatitis C virus in the colon tissue and its relationship with hepatitis C virus pathogenesis.

Research Abstract
Format: Abstract Send to J Med Microbiol. 2016 Aug;65(8):703-12. doi: 10.1099/jmm.0.000272. Epub 2016 May 10. Extra-hepatic infection of hepatitis C virus in the colon tissue and its relationship with hepatitis C virus pathogenesis. Hetta HF1, Mekky MA2, Khalil NK3, Mohamed WA4, El-Feky MA4, Ahmed SH4, Daef EA4, Medhat A2, Nassar MI5, Sherman KE6, Shata MT6. Author information Abstract Extra-hepatic compartments might contribute to hepatitis C virus (HCV) persistence and extra-hepatic manifestations. Therefore, we investigated HCV infection in colonic tissue in patients with chronic hepatitis C (CHC) and its relationship with HCV pathogenesis. Colonic biopsies were collected from three groups with CHC infection: treatment naïve (TN; n=12), non-responders (NR; n=10) to anti-HCV therapy (pegylated interferon-α and ribavirin) and sustained virologic response (SVR; n=10) and from a fourth healthy control group (n=10). Liver biopsies were examined to assess inflammation and fibrosis. HCV infection and colonic T regulatory (Treg) frequency were detected by immunohistochemistry. HCV core and NS3 proteins were detected in B cells and macrophage/monocytes of 42 % and 25 % of TN and 50 % and 30 % of NR, respectively, but not in SVR or control group. The numbers of cells expressing HCV proteins were positively correlated with both HCV viral load and colonic Treg frequency. A significant negative correlation between HCV-expressing cells with both liver inflammation and fibrosis was identified. Our study provides evidence that HCV can infect B cells and macrophages of the colon. The correlations between HCV infection in colonic tissue and HCV viral load and liver pathology underline the significance of this extra-hepatic infection in HCV pathogenesis and response to therapy. PMID: 27166142 PMCID: PMC5756491 DOI: 10.1099/jmm.0.000272 [Indexed for MEDLINE] Free PMC Article
Research Authors
Hetta HF1, Mekky MA2, Khalil NK3, Mohamed WA4, El-Feky MA4, Ahmed SH4, Daef EA4, Medhat A2, Nassar MI5, Sherman KE6, Shata MT6.
Research Journal
J Med Microbiol. 2016 Aug;65(8):703-12. doi: 10.1099/jmm.0.000272. Epub 2016 May 10.
Research Pages
703-12
Research Publisher
NULL
Research Rank
1
Research Vol
(8):703-12.
Research Website
pub. med.
Research Year
2016
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