ABSTRACT
Vascular endothelial growth factor (VEGF) is expressed at elevated levels by most cancer cells, which can stimulate vascular endothelial cell growth, survival, proliferation as well as trigger angiogenesis modulated by VEGF and VEGFR (a tyrosine kinase receptor) signaling. The angiogenic effects of the VEGF family are thought to be primarily mediated through the interaction of VEGF with VEGFR-2. Targeting this signaling molecule and its receptor is a novel approach for blocking angiogenesis. In recent years virtual high throughput screening has emerged as a widely accepted powerful technique in the identification of novel and diverse leads. The high resolution X-ray structure of VEGF has paved the way to introduce new small molecular inhibitors by structure-based virtual screening. In this study using different alkaloid molecules as potential novel inhibitors of VEGF we proposed three alkaloid candidates for inhibiting VEGF and VEGFR mediated angiogenesis. As these three alkaloid compounds exhibited high scoring functions, which also highlights their high binding ability, it is evident that these alkaloids can be taken to further drug development pipelines for use as novel lead compounds to design new and effective drugs against cancer.
ABSTRACT
Vascular endothelial growth factor (VEGF) is expressed at elevated levels by most cancer cells, which can stimulate vascular endothelial cell growth, survival, proliferation as well as trigger angiogenesis modulated by VEGF and VEGFR (a tyrosine kinase receptor) signaling. The angiogenic effects of the VEGF family are thought to be primarily mediated through the interaction of VEGF with VEGFR-2. Targeting this signaling molecule and its receptor is a novel approach for blocking angiogenesis. In recent years virtual high throughput screening has emerged as a widely accepted powerful technique in the identification of novel and diverse leads. The high resolution X-ray structure of VEGF has paved the way to introduce new small molecular inhibitors by structure-based virtual screening. In this study using different alkaloid molecules as potential novel inhibitors of VEGF we proposed three alkaloid candidates for inhibiting VEGF and VEGFR mediated angiogenesis. As these three alkaloid compounds exhibited high scoring functions, which also highlights their high binding ability, it is evident that these alkaloids can be taken to further drug development pipelines for use as novel lead compounds to design new and effective drugs against cancer.
ABSTRACT
Objective: To assess the efficacy of tacrolimus and clobetasol propionate in the treatment of alopecia areata
Methods A clinical trial was carried out in the department of Dermatology and Venereology, Dhaka Medical College Hospital, Dhaka, Bangladesh from May 2013 to April 2014. Total sixty patients were enrolled and divided into group A and group B. Thirty of group A patients were treated with topical tacrolimus and thirty of group B patients were treated with topical clobetasol propionate
Results: In group A, the duration of illness ranged from 2 months to 36 months and in group B, from 1 month to 24 months. Among the patients of group A and B, 25 [83.3%] and 27 [90%] patients improved, respectively. After 16th week of treatment, slight response in 6 [20%] and 4 [13.3%] and moderate response in 18 [59.4%] and 22 [63.2%] and marked response in 1 [3.3%] and 1 [3.3%] was seen in group A and group B, respectively. No significant difference was observed [p value = 0.648]
Conclusion: Both the drugs, clobetasol propionate and tacrolimus when used individually, were found to be equally effective in the treatment of alopecia areata and tacrolimus ointment 0.1% can be used as an alternate therapeutic modality