Browsing by Author "Omar, NN"

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    Structure-based design generated novel hydroxamic acid based preferential HDAC6 lead inhibitor with on-target cytotoxic activity against primary choroid plexus carcinoma
    (TAYLOR & FRANCIS LTD, 2019-01) Kassab, SE; Mowafy, S; Alserw, AM; Seliem, JA; El-Naggar, SM; Omar, NN; Awad, MM
    Histone deacetylase 6 (HDAC6) is an attractive target for cancer therapeutic intervention. Selective HDAC6 inhibitors is important to minimise the side effects of pan inhibition. Thus, new class of hydroxamic acid-based derivatives were designed on structural basis to perform preferential activity against HDAC6 targeting solid tumours. Interestingly, 1-benzylbenzimidazole-2-thio-N-hydroxybutanamide 10a showed impressive preference with submicromolar potency against HDAC6 (IC50 = 510 nM). 10a showed cytotoxic activity with interesting profile against CCHE-45 at (IC50 = 112.76 mu M) when compared to standard inhibitor Tubacin (IC50 = 20 mu M). Western blot analysis of acetylated-alpha-tubulin verified the HDAC6 inhibiting activity of 10a. Moreover, the insignificant difference in acetylated-alpha-tubulin induced by 10a and Tubacin implied the on-target cytotoxic activity of 10a. Docking of 10a in the binding site of HDAC6 attributed the activity of 10a to pi-pi stacking with the amino acids of the hydrophobic channel of HDAC6 and capture of zinc metal in bidentate fashion. The therapeutic usefulness besides the on-target activity may define 10a as an interesting safe-lead inhibitor for future development.
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    TUMOR POTENTIAL IN RAT WOUNDS AFTER SHORT- AND LONG-TERM ADMINISTRATION OF PLATELET-RICH PLASMA
    (BIOLIFE SAS, 2017-12) El Bakly, W; Mahmoud, NA; Shoukry, Y; Tash, RF; El-Tawdi, AH; Omar, NN
    Platelet-rich plasma (PRP) has been recognized as an effective strategy for tissue regeneration, however, the safety of PRP in wound healing in terms of tumorigenicity has not yet been addressed. Therefore, the aim of this study was to examine the impact of PRP administration on the expression of the inflammatory marker, tenascin-C (TnC) and the myofibroblast markers, alpha-smooth muscle actin (alpha-SMA) and vimentin. The immune suppressive response was examined by determining the level of forkhead box protein 3 (Foxp3). PRP was administered for both long-term (two times weekly for four weeks) and short-term (for the fourth week only) post-wounding. Collagen I (col1) and lysyl oxidase (LOX) were used to indicate complete healing, after which any increase in the myofibroblast or in the inflammatory markers would suggest tumor potential. Collagen III (col3), a marker for granulation tissue, was used to remark non-healing. Quantitative real-time reverse transcriptase polymerase chain reaction (QRTPCR) and Western blot showed that after long-term administration of PRP, the expression of TnC, a- SMA and vimentin was barely detected, while being markedly expressed in the wounded non-treated group and in the short-term administration group. Moreover, the active expression of a- SMA in the two groups was associated positively with the expression of col3 and negatively with the expression of col1. The low expression of Foxp3 after short-term administration relative to the control group indicated active immunity against tumor development. In conclusion, these findings indicate that PRP can be safely used in short- and long-term administration without tumorigenesis concern.